VA/DoD Clinical Practice Guideline: The Non-Surgical Management of Hip & Knee Osteoarthritis (OA)

VA/DOD CLINICAL PRACTICE GUIDELINE FOR THE NON-SURGICAL MANAGEMENT OF HIP & KNEE OSTEOARTHRITIS

OF HIP & KNEE OSTEOARTHRITIS

Department of Veterans Affairs

Department of Defense

QUALIFYING STATEMENTS

The Department of Veterans Affairs (VA) and the Department of Defense (DOD) guidelines are based on the best information available at the time of publication. The guidelines are designed to provide information and assist decision-making. They are not intended to define a standard of care and should not be construed as such, nor should the guidelines be interpreted as prescribing an exclusive course of management.

This clinical practice guideline (CPG) is based on a systematic review of both clinical and epidemiological evidence. Developed by a panel of multidisciplinary experts, it provides a clear explanation of the logical relationships between various care options and health outcomes while rating both the quality of the evidence and the strength of the recommendation.

Variations in practice will inevitably and appropriately occur when providers consider the needs of individual patients, available resources, and limitations unique to an institution or type of practice. Therefore, every health care professional using these guidelines is responsible for evaluating the appropriateness of applying them in each unique clinical situation using a patient-centered approach.

These guidelines are not intended to represent VA or DOD policies. Further, inclusion of recommendations for specific testing, therapeutic interventions, or both, within these guidelines does not guarantee coverage of civilian sector care.

Version 3.0 – 2026

VA/DOD Clinical Practice Guideline for the Non-Surgical Management of Hip & Knee Osteoarthritis

Prepared by:

The Non-Surgical Management of Hip & Knee Osteoarthritis

Work Group

With support from:

Office of Quality and Patient Safety, Veterans Health Administration

and Clinical Quality Improvement Program, Defense Health Agency

Version 3.0 – 2026

Based on evidence reviewed through July 31, 2025

Table of Contents

I. Introduction ........................................................................................................................ 6

II. Background ........................................................................................................................ 6

A. Epidemiology and Cost of Osteoarthritis ......................................................................... 6

B. Disease Course, Clinical Presentation, and Risk Factors for Osteoarthritis ..................... 8

C. Prevention Strategies for Osteoarthritis .......................................................................... 9

D. Osteoarthritis Force Readiness .................................................................................... 10

III. Scope of This Guideline ................................................................................................... 10

A. Guideline Audience ...................................................................................................... 10

B. Guideline Population .................................................................................................... 10

IV. Highlighted Features of This Guideline ........................................................................... 11

A. Highlights in This Guideline Update .............................................................................. 11

B. Components of This Guideline ..................................................................................... 11

C. Demographic Terminology in This Guideline ................................................................ 11

V. Guideline Development Team .......................................................................................... 11

VI. Summary of Guideline Development Methodology ........................................................ 13

A. Evidence Quality and Recommendation Strength ......................................................... 14

B. Categorization of Clinical Practice Guideline Recommendations ................................... 15

C. Management of Potential or Actual Conflicts of Interest ................................................ 16

D. Patient Perspective ...................................................................................................... 16

E. External Peer Review .................................................................................................. 17

F. Implementation ............................................................................................................ 17

VII. Approach to Care in the Department of Veterans Affairs and the Department of

Defense ............................................................................................................................. 18

A. Patient-Centered Care ................................................................................................. 18

B. Shared Decision-Making .............................................................................................. 18

C. Patients with Co-Occurring Conditions ......................................................................... 18

VIII. Algorithm .......................................................................................................................... 19

Module A. Management and Treatment of Osteoarthritis of the Hip and/or the Knee ............ 20

IX. Recommendations ........................................................................................................... 23

A. Diagnosis .................................................................................................................... 27

B. Lifestyle-Based Interventions ....................................................................................... 29

C. Physical Therapy ......................................................................................................... 32

D. Devices ....................................................................................................................... 37

E. Pharmacotherapy ........................................................................................................ 41

F. Orthobiologics.............................................................................................................. 55

G. Interventional Procedures ............................................................................................ 64

H. Dietary Supplements and Nutraceuticals ...................................................................... 69

I. Complementary and Integrative Health ........................................................................ 71

X. Research Priorities ........................................................................................................... 78

A. Distinguishing Pain Phenotypes to Improve Treatment Targeting in Osteoarthritis ........ 78

B. Long-term Studies and Comparative Effectiveness Research ....................................... 79

C. Lifestyle-Based Interventions ....................................................................................... 79

D. Physical Therapy ......................................................................................................... 79

E. Devices ....................................................................................................................... 79

F. Pharmacotherapy ........................................................................................................ 80

G. Evidence to Support the Safe and Effective Use of Orthobiologic Therapies and Other

Emerging Biologic Treatments for Osteoarthritis ........................................................... 80

H. Interventional Procedures ............................................................................................ 81

I. Dietary Supplements and Nutraceuticals in Osteoarthritis ............................................. 81

J. Complementary and Integrative Health ........................................................................ 81

K. Psychological Interventions .......................................................................................... 81

Appendix A: Guideline Development Methodology ............................................................... 82

A. Developing Key Questions to Guide the Systematic Evidence Review .......................... 82

B. Conducting the Systematic Review .............................................................................. 86

C. Developing Evidence-Based Recommendations .......................................................... 92

D. Recommendation Categorization ................................................................................. 94

E. Drafting and Finalizing the Guideline ............................................................................ 95

Appendix B: Evidence Table ................................................................................................... 97

Appendix C: 2020 Recommendation Categorization ........................................................... 104

Appendix D: Participant List ................................................................................................. 108

Appendix E: Patient Focus Group Methods and Findings................................................... 110

A. Methods .................................................................................................................... 110

B. Patient Focus Group Findings .................................................................................... 110

Appendix F: Literature Review Search Terms and Strategy ................................................ 112

A. Resources Searched ................................................................................................. 112

B. Search Strategies ...................................................................................................... 112

Appendix G. Alternative Text Descriptions of Algorithm ..................................................... 120

Module A: Management and Treatment of Osteoarthritis of the Hip and/or the Knee .......... 120

Appendix H. Patient History and Physical Examination ...................................................... 121

A. Knee and Hip Osteoarthritis Risk Factors ...................................................................... 121

C. Knee Osteoarthritis Patient History ............................................................................. 122

D. Hip Osteoarthritis Patient History................................................................................ 122

Appendix I. Pharmacotherapy............................................................................................... 124

Chronic Pain in Veterans – Sensibly Selecting OA Pharmacotherapy ................................ 124

Appendix J. Nutraceuticals and Dietary Supplements......................................................... 130

Avocado and Soybean Unsaponifiables (ASU) .................................................................. 130

Boswellia Serrata (BS) Extract .......................................................................................... 130

Cannabinoid (CBD) Products ............................................................................................ 130

Chondroitin, Glucosamine, and Glucosamine plus Chondroitin .......................................... 131

Curcumin .......................................................................................................................... 131

Collagen ........................................................................................................................... 132

Methylsulfonylmethane (MSM) .......................................................................................... 132

Omega-3 Fatty Acids ........................................................................................................ 133

Pycnogenol (Pine Bark) .................................................................................................... 133

Rosehip ............................................................................................................................ 133

Traditional Chinese Medicine ............................................................................................ 133

Vitamin D.......................................................................................................................... 134

Vitamin E .......................................................................................................................... 134

Willow Bark Extract ........................................................................................................... 134

Appendix K. Referrals for Surgical Consultation ................................................................. 135

Appendix L: Osteoarthritis Education .................................................................................. 136

Nonpharmacologic Approaches for Knee and Hip Osteoarthritis ........................................ 136

Appendix M: Tools used to Measure Activity Level in Osteoarthritis ................................. 137

Performance Based Measures .......................................................................................... 137

Patient-Reported Outcome Measures (PROMs) ................................................................ 138

Appendix N: Abbreviation List .............................................................................................. 141

References ............................................................................................................................. 145

I. Introduction

The Department of Veterans Affairs (VA) and Department of Defense (DOD) Evidence-Based Practice Work Group (EBPWG) was established in 2004, with a mission to use clinical and epidemiological evidence to improve population health within the Veterans Health Administration (VHA) and Military Health System (MHS) and develop clinical practice guidelines (CPGs) for the VA and DOD populations.(1) The development and updating of VA/DOD CPGs is funded by VA Evidence Based Practice, Office of Quality and Patient Safety. The system-wide goal of evidence-based guidelines, including this CPG, is to guide providers in non-surgical osteoarthritis management in addition to offering management pathways supported by evidence. This CPG is intended to provide health care providers with a practical framework by which to evaluate, treat, and manage osteoarthritis, address the individual needs and preferences of patients, and improve clinical outcomes.

In 2014, the VA and DOD published a CPG for the Non-Surgical Management of Hip & Knee Osteoarthritis (2014 VA/DOD OA CPG), which was based on evidence reviewed from January 2002 through December 2012. This was updated in 2020 using the same process, based on evidence reviewed through June 3, 2019 (2020 VA/DOD OA CPG). Since then, a growing body of research has expanded the general knowledge and understanding of the impact of non-surgical management interventions on hip and knee osteoarthritis. Consequently, a recommendation to update the 2020 OA CPG was initiated in April 2025 using published data from June 3, 2019, to July 31, 2025. This updated CPG’s use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach reflects a more rigorous application of the methodology than previous iterations.(2) Therefore, the strength of some recommendations might have been modified because of changes in the quality of the supporting evidence (see Evidence Quality and Recommendation Strength).

This CPG provides an evidence-based framework for evaluating and managing adults, 18 years or older, with osteoarthritis of the hip or knee who are eligible for care in the VA or DOD systems, including community care. These guidelines were written to emphasize the role of:

• Utilizing patient-centered care;
• Decreasing preventable complications and morbidity;
• Improving health outcomes and quality of life (QoL); and
• Using shared decision-making frameworks in patient collaboration efforts.

II. Background

A. Epidemiology and Cost of Osteoarthritis

Osteoarthritis (OA) is one of the most common chronic conditions worldwide and in the United States (U.S.). According to the Centers for Disease Control and Prevention (CDC), OA affects more than 30 million Americans (3) with prevalence estimates of 13.9% of adults age 25 years and older, and 33.6% of adults age 65 years and older.(4) However, the prevalence and incidence rates vary across studies depending on the definition of OA (e.g., radiographic, symptomatic, self- reported, or provider-diagnosed) and study setting (e.g., clinical or population-based). The epidemiology of OA also differs by sex, age distribution, body weight, and race. Osteoarthritis is more common in women, with worldwide estimates of symptomatic OA of 18% in women and 9.6% in men over 60 years of age.(5) OA increases after 50 years of age, the knee is the most common site, and studies generally indicate that OA is more common in Blacks compared to Whites.(6)

It is estimated that, at large, one in two patients may develop symptomatic knee OA (KOA) in their lifetime,(7) and one in four may develop symptomatic hip OA (HOA) in their lifetime.(8) Obesity increases the lifetime risk of OA significantly; two out of three people with obesity will develop OA.(9) By 2040, the number of U.S. adults with provider-diagnosed arthritis is projected to increase 49% to 78.4 million (25.9% of all adults), and the number of adults with arthritis- attributable activity limitation will increase 52% to 34.6 million (11.4% of all adults).(10)

OA is more common in military Service Members and Veterans than in the general population. A 2013 CDC study estimated that 25.6% of Veterans have arthritis and incidence rates increase with age.(11) One study found that OA was more common in Veterans compared to non-veterans with a prevalence of 25.6% and 23.6%, respectively. In another study, the overall incidence rate for physician-diagnosed OA in Active-Duty Service Members was 7.9 cases per 1,000 person- years (95% confidence interval [CI]: 7.82-7.91).(12) The adjusted incidence rate for OA was approximately 20% higher in women Service Members compared to men (relative risk [RR]: 1.19, 95% CI: 1.17-1.21) and age was a significant risk factor. Between 1999 and 2008 there was a 19- fold higher incidence of OA in Active-Duty Service Members greater than 40 years of age compared to those less than 20 years of age (no specific military-only forecast exists in the recent published data).(12)

Active-Duty Service Members regularly experience repetitive joint loading during physical activity and military tasks and activities. Military-service-related overuse, as well as traumatic and non- traumatic joint injuries, are contributing factors to an increased risk of developing osteoarthritis.(13) Military rank and branch of military service may also correlate with variation in the incidence of OA. For example, junior and senior enlisted Service Members and those serving in the Army experienced the highest incidence rates for OA.(12) Additionally, Service Members tend to develop OA at an earlier age with a recent article reporting that one in six military officers in the U.S. who suffered a knee injury developed OA by the age of 30.(14)

The large use of healthcare resources to manage OA contributes significantly to healthcare costs.(15-17) In fact, the medical costs related to OA account for an estimated 1-2.5% of the gross domestic product of high-income countries.(18) Overall, the economic burden of OA and related conditions exceeded an estimated $340 billion annually in direct healthcare costs. The combination of direct and indirect costs for OA and related disorders is estimated to be $461 billion.(19) Hip and knee joint replacements represent a major portion of these costs.(18) The indirect costs associated with OA greatly surpass healthcare costs and exert significant personal costs for people with OA due to work loss and premature retirement, leading to loss of income and subsequent reductions in personal savings.(18)

Osteoarthritis is associated with substantial disability, with epidemiologic data indicating that up to 80% of affected individuals experience limitations in movement and nearly 25% have difficulty performing activities of daily living.(5,20,21) Hip and knee OA are leading causes of disability worldwide accounting for 2.4% of all years lived with disability (YLDs), an overall measure of disease burden.(22) From 1990-2016, OA was in the top 20 contributors to YLDs and ranked second to diabetes as the condition associated with the most rapid increases in disability, with a 46% increase in YLDs.(23) By 2020, OA is expected to be the fourth leading cause of YLDs globally.(18) OA is second to back pain as the most common cause of military separation, and it leads to significant disability during peacetime and war.(24)

OA has negative impacts on physical health that may also influence a patient's QoL and mental health.(25) Depression and catastrophizing commonly affect patients with OA.(26,27) Sleep disturbances were found in 72% of adults >55 years with OA.(28) Additional OA-related sequelae can include muscle weakness, instability, and balance problems that can lead to falls and development of other comorbid musculoskeletal conditions as musculoskeletal conditions often coexist (e.g., fibromyalgia).(29)

B. Disease Course, Clinical Presentation, and Risk Factors for Osteoarthritis

OA of the hip and knee represents a chronic disease with a slow, progressive course. OA becomes more common with age and is diagnosed at a median age of 55 years.(30) Unilateral OA may progress to bilateral OA over time, and bilateral joint involvement is more common in patients with advanced OA.(31) HOA is frequently unilateral.

Patients with OA of the hip and knee may present with minimal symptoms or incidental findings on physical examination (bony enlargement, crepitus, joint swelling, or decreased range of motion) or radiographic abnormalities (osteophyte formation or joint space narrowing). Patients with symptomatic KOA usually present with knee pain and stiffness. Thigh muscle wasting and bony enlargement may occur with severe OA. Inflammation is usually absent or only modest, although small to medium-sized effusions are common at the knee.(32) Patients with HOA frequently present with pain in the groin that can radiate to the anterior thigh or buttock.(33)

Typically, joint pain in the hip or knee is exacerbated by activity and relieved by rest.(34) Over time, OA of the hip and knee can progress to severe, disabling pain that can occur at rest. When the pain becomes severe, it can interfere with sleep and limit a patient’s ability to walk, stand for prolonged periods, or climb stairs.(35) Joint stiffness is usually brief (less than 30 minutes) and occurs in the morning or after periods of inactivity.

Risk factors for OA of the hip and knee can be categorized as patient- or joint-related factors. Patient-related risk factors include older age, female sex, obesity, genetic predisposition, and engagement in work or recreational activities that involve repetitive joint loading over time.(36,37) Obesity is a strong, modifiable risk factor, especially for KOA.(37) Physical training, military tasks, and activities or work that requires frequent kneeling, heavy lifting, or heavy physical loads on joints are associated with OA development.(38,39) Studies also show a strong association between high-impact sports (e.g., football, hockey) and the development of OA.(40,41) Notably, there was a dose-response relationship with strenuous sports and risk of OA. Only participants in the highest tertile of participation in strenuous sports or exercise had an increased risk for OA.(42)

Joint-related factors also contribute to the development of OA. These factors include prior joint injury (e.g., ligament or meniscal damage, trauma), joint malalignment or deformities, joint laxity, increased bone density, and abnormal joint loading.(43,44) Less well-defined potential risk factors for OA development include knee extensor muscle weakness and smoking.(45)

C. Prevention Strategies for Osteoarthritis

Preventing OA has been a rich area of research, though efficacy has been variable or limited. Several reviews have found little evidence for preventing OA (46-50) despite some basic science trials showing promise.(46)

While obesity is a modifiable risk factor for developing OA, there is inconsistency in the literature exploring the efficacy of weight loss in preventing OA. Mechanistically, losing 1 pound (lb) can reduce load on the knee by 4lbs,(51) and, empirically, the Framingham study found that a decrease in Body Mass Index (BMI) ≥2 reduces one’s risk for OA by >50%.(52) Similar to the Framingham study, one cohort of nearly 800 women found that a 5.1 kilogram (kg) weight loss reduced the risk of radiographic progression of KOA by >50% over 10 years.(53) However, most literature exploring the effects of weight loss on OA assesses symptom reduction, not radiographic changes,(54) and there’s been no direct evidence showing that weight loss prevents OA.(49)

Considering the impact of physical activity on OA development, one must consider the volume and intensity of exertion. A United Kingdom community-based cohort study tracking participants without OA at baseline over an average of 11 years found increased risk for developing OA in participants active in strenuous sports (Hazard Ratio [HR] 1.34), in physically demanding jobs (HR 1.25), and with jobs requiring mainly walking or standing (HR 1.23). In contrast, walking for pleasure (HR 0.93) and walking to work (HR 0.91) predicted a lower risk of developing OA.(42) Similarly, a randomized controlled trial (RCT) assessing a combination of exercise, diet, and glucosamine on OA prevention in obese women did not find a significantly lower risk of OA development over 2.5 years.(55) Indirect evidence, such as the association of quadriceps atrophy and KOA suggests that exercise may be protective against OA by maintaining normal joint function and preventing maladaptive joint loading.(56)

Focusing on diet, data is limited in the context of OA prevention. One prospective cohort of the Osteoarthritis Initiative found that a Western diet was associated with radiographic and symptomatic progression of OA at 4 years of follow up.(57) A systematic review (SR) of the Mediterranean diet and OA found that higher adherence to the Mediterranean diet was associated with lower prevalence of KOA.(58) In contrast, another systematic review found that dietary interventions were not effective in the prevention of KOA.(59) This variability may be due to heterogeneity in the diets themselves or in the methodology and outcome measures of these studies. Diet remains an area of interest in OA prevention given its role in weight management.

Nutraceuticals have gained interest as potential disease modifying osteoarthritis drugs (DMOADs). Curcumin has shown some anti-inflammatory properties in in-vitro studies, but in vivo studies are lacking.(60-62) Similarly, polyunsaturated fatty acids have shown some success in reducing inflammation in vitro and reducing OA in rats, but not in humans.(63) Chondroitin may reduce joint space loss by 0.28 millimeter (mm) at best but doesn’t consistently reduce pain more than placebo.(64-67) Glucosamine has been reported to reduce joint space loss by at most 0.51mm.(66,68,69) However, reductions in joint space loss have not consistently been shown to correlate with clinically significant improvements in function or pain scores.(66,68,69) Hyaluronic acid (HA) also showed mixed efficacy with just one study showing <3% difference in rate of knee cartilage loss (70) and no significant change in other trials.(71,72) Studies exploring non-steroidal anti-inflammatory drug (NSAIDs),(66,72-74) vitamin D,(75) and vitamin E (75,76) failed to show effect in OA prevention. One review exploring nutraceuticals as prevention for OA failed to find any studies meeting their inclusion criteria for S-adenosylmethionine, methylsulfonylmethane (MSM), vitamin C, or platelet-rich plasma (PRP).(77)

Considering avenues for future research, Losina et al. (2014) created a cost-efficacy model for DMOADs suggesting that a candidate DMOAD would need to cost less than $3000 per year to be cost-effective assuming 40% efficacy, 5% failure rate per year, and an increase in 0.04 quality- adjusted life year (QALYs).(78) Messier et al. (2024) have started a phase III assessor-blind 48 month RCT exploring the effects of weight loss, exercise, and weight-loss maintenance on OA progression with radiographic progression on Magnetic Resonance Imaging (MRI) as the primary endpoint in women at risk for OA but who have not yet developed OA.(79) The approach of targeting “pre-OA” has been suggested by others who have failed to find efficacy in OA prevention.(80)

D. Osteoarthritis Force Readiness

Osteoarthritis is a common cause of disability in military populations and remains an important contributor to duty limitation and medical separation. Active-Duty Service Members face unique OA risks related to repetitive joint loading, occupational demands, traumatic joint injury, and post- traumatic osteoarthritis.(13,24) Consistent with the Defense Health Agency’s role as a Combat Support Agency, effective OA management supports warfighter medical readiness by preserving function, reducing duty-limiting pain, and facilitating return to mission-capable status.(81) These guidelines emphasize early identification, structured exercise-based therapy, physical therapy, weight management when appropriate, and shared decision-making to improve function and reduce unnecessary invasive interventions.(82-85) Timely, evidence-based conservative care helps sustain deployability, force generation, and operational readiness across the Joint Force.(81-85)

III. Scope of This Guideline

This CPG is based on published clinical evidence and related information available between June 3, 2019, to July 31, 2025. It is intended to provide general guidance on best evidence-based practices (see Appendix A for additional information on the evidence review methodology). Although the CPG is intended to improve the quality of care and clinical outcomes (see Introduction), it is not intended to define a standard of care (i.e., mandated or strictly required care).

A. Guideline Audience

This CPG is intended for use by providers who manage, co-manage, or otherwise care for adults with osteoarthritis of the hip or knee.

B. Guideline Population

This CPG is intended for adults (18 years or older) with osteoarthritis of the hip or knee who are eligible for care in the VA or DOD systems, including community care.

IV. Highlighted Features of This Guideline

A. Highlights in This Guideline Update

The current document is an update to the 2020 VA/DOD OA CPG. The major strength of this CPG is in the coordination and collaboration of the multidisciplinary team, ensuring a broad representation of providers engaged in osteoarthritis management. The following significant updates highlight the importance of clinicians reviewing this version of the CPG:

 Updated Algorithm;

 Updated Sidebars; and

 Added 11 new recommendations, reviewed and replaced 11 recommendations, reviewed and amended 8 recommendations and carried over 2 recommendations not changed from the 2020 VA/DOD Osteoarthritis CPG.

The methodology used in developing this CPG reflects a more rigorous application of the GRADE methodology than previous versions. The result is a refined CPG that includes methodologically rigorous, evidence-based recommendations for non-surgical management of osteoarthritis of the hip or knee. This CPG also provides expanded recommendations on research needed to strengthen future guidelines.

B. Components of This Guideline

This CPG provides clinical practice recommendations for patients who would benefit from non- surgical management of osteoarthritis of the hip or knee (see Recommendations). In addition, the Algorithm integrates the recommendations in the context of the flow of patient care. This CPG also includes Research Priorities, which list areas the Work Group identified as needing additional research. To accompany this CPG, the Work Group also developed toolkit materials for providers and patients, including a provider summary, patient summary, and quick reference guide, which can be found at https://www.healthquality.va.gov/index.asp.

C. Demographic Terminology in This Guideline

The demographic terms used in this guideline are derived from the published literature sources included in the SR and evidence base. The Work Group used terms such as Black rather than African American and White rather than Caucasian to avoid presumptions about ancestry and improve clarity and consistency. To accurately present the research evidence on which this CPG is based, the Work Group made every effort to use the same terminology as reported in the published literature base of SRs, clinical trials, and other studies. Consequently, usage of demographic terms in this CPG may vary and appear inconsistent.

V. Guideline Development Team

The VA Evidence Based Practice, Office of Quality and Patient Safety, in collaboration with the Clinical Quality Improvement Program, Defense Health Agency, identified the following four providers to serve as Champions (i.e., leaders) of this CPG’s Work Group: Jennifer Ault, MS, DPT, DO and Jason Guevara, MD, from VA; and Jess Edison, MD and Bryan Pickens, PT, DSc, FAAOMPT from DOD. The Work Group was comprised of individuals with the following areas of expertise: pain management, orthopedics, primary care, rheumatology, clinical pharmacy, internal medicine, physical therapy, nursing, and dietetics. Table 1 lists the Work Group and Guideline Development Team members.

This CPG Work Group, led by the Champions, was tasked with:

 Determining the scope of the CPG;

 Crafting clinically relevant key questions (KQs) to guide the systematic evidence review;

 Identifying discussion topics for the Patient Focus Group and considering the patient perspective;

 Providing direction on inclusion and exclusion criteria for the systematic evidence review and the assessment of the level and quality of evidence; and

 Developing evidence-based clinical practice recommendations, including determining the strength and category of each recommendation.

Sigma Health Consulting and Duty First Consulting were contracted by the VA to help develop this CPG.

Table 1. Guideline Work Group and Guideline Development Team

*Additional contributor contact information is available in Appendix D

VI. Summary of Guideline Development Methodology

The methodology used in developing this CPG follows the Guideline for Guidelines, an internal document of the VA/DOD EBPWG updated in January 2019 that outlines procedures for developing and submitting VA/DOD CPGs.(86) The Guideline for Guidelines is available at http://www.healthquality.va.gov/policy/index.asp. This CPG also aligns with the National Academy of Medicine’s (NAM) principles of trustworthy CPGs (e.g., explanation of evidence quality and strength, management of potential conflicts of interest [COI], interdisciplinary stakeholder involvement, use of SR and external review).(87) Appendix A provides a detailed description of the CPG development methodology.

A. Evidence Quality and Recommendation Strength

The Work Group used the GRADE approach to craft each recommendation and determine its strength. Per the GRADE approach, recommendations must be evidence-based and cannot be made based on expert opinion alone. The GRADE approach uses the following four domains to inform the strength of each recommendation (see Determining Recommendation Strength and Direction)(88):

• Balance of desirable and undesirable outcomes
• Confidence in the quality of the evidence
• Patient or provider values and preferences
• Other implications, as appropriate (e.g., resource use, equity, acceptability, feasibility, subgroup considerations)

Using these four domains, the Work Group determined the relative strength of each recommendation (Strong or Weak). The strength of a recommendation is defined as the extent to which one can be confident that the desirable effects of an intervention outweigh its undesirable effects and is based on the framework above, which incorporates the four domains.(89) A Strong recommendation generally indicates High or Moderate confidence in the quality of the available evidence, a clear difference in magnitude between the benefits and harms of an intervention, similar patient values and preferences, and understood influence of other implications (e.g., resource use, feasibility). A recommendation’s strength (i.e., Strong vs. Weak) does not reference its clinical importance (e.g., a Weak recommendation is evidence-based and still important to clinical care).

In some instances, the systematic evidence review might have found little or no relevant evidence, inconclusive evidence, or conflicting evidence for a particular therapy or intervention. The way this finding is expressed in the CPG might vary. The Work Group might include a statement among its recommendations acknowledging insufficient evidence for or against a commonly practiced intervention, particularly if it lacks supporting clinical evidence and poses potential risks (e.g., high opportunity cost, misallocation of resources). In other cases, the Work Group might choose to remain silent in cases evidence is lacking for a rarely used intervention or when an intervention, despite the absence of recent evidence, is considered the standard of care and has a favorable balance of benefits and harms.

Using these elements, the Work Group determines the strength and direction of each recommendation and formulates the recommendation with the general corresponding text as shown in Table 2. The strength of each recommendation is shown in Recommendations.

Table 2. Strength and Direction of Recommendations and General Corresponding Text

This CPG’s use of GRADE reflects a more rigorous application of the methodology than previous iterations; the determination of the strength of the recommendation is more directly linked to the confidence in the quality of the evidence on outcomes that are critical to clinical decision-making. The confidence in the quality of the evidence is assessed using an objective, systematic approach independent of the clinical topic of interest. Therefore, recommendations on topics for which designing and conducting rigorous studies (e.g., RCTs), might be inherently more difficult, are typically considered lower quality evidence and, in turn, are usually Weak recommendations. Recommendations on topics for which rigorous studies can be designed and conducted (e.g., RCTs) may more often be Strong recommendations. Per GRADE, if the quality of evidence differs across the relevant critical outcomes, the lowest quality of evidence for any of the critical outcomes determines the overall quality of the evidence for a recommendation.(2,90) This stricter standard provides a consistent approach to determining recommendation strengths. For additional information on GRADE or CPG methodology, see Appendix A.

B. Categorization of Clinical Practice Guideline Recommendations

Evidence-based CPGs should be current. Except for an original version of a new CPG, staying current typically requires revision of a CPG’s previous versions based on new evidence or as scheduled subject to time-based expirations.(91) For example, the U.S. Preventative Services Task Force (USPSTF) has a process for monitoring the emergence of new evidence that could prompt an update of its recommendations, and it aims to review each topic at least every five years for either an update or reaffirmation.(92)

Recommendation categories are used to track how the previous CPG’s recommendations could be reconciled. These categories and their corresponding definitions are similar to those used by the National Institute for Health and Care Excellence (NICE, U.K.).(93,94) Table 3 lists these categories, which are based on whether the evidence supporting a recommendation was systematically reviewed, the degree to which the previous CPG’s recommendation was modified, and whether a previous CPG’s recommendation is relevant in the updated CPG.

Additional information regarding these categories and their definitions can be found in Recommendation Categorization. The 2025 VA/DOD OA CPG recommendation categories can be found in Recommendations. Appendix C outlines the 2020 VA/DOD OA CPG’s recommendation categories.

Table 3. Recommendation Categories and Definitions*

*Adapted from the NICE guideline manual (2012)(93) and Garcia et al. (2014)(94)

Abbreviations: CPG: clinical practice guideline

C. Management of Potential or Actual Conflicts of Interest

Management of COIs for the CPGs is conducted as described in the Guideline for Guidelines.(86) Further, the Guideline for Guidelines refers to details in the VHA Handbook 1004.07 Financial Relationships between VHA Health Care Professionals and Industry (November 2014, issued by the VHA National Center for Ethics in Health Care)(95) as well as to disclosure statements (i.e., standard disclosure form completed at least twice by CPG Work Group members and the guideline development team).(86) The disclosure form inquires about relevant financial and intellectual interests or other relationships with, for example, manufacturers of commercial products, providers of commercial services, or other commercial interests. The disclosure form also asks about any other relationships or activities that could be perceived to have influenced, or give the appearance of potentially influencing, a respondent’s contributions to the CPG. In addition, instances of potential or actual COIs among the CPG Work Group and the guideline development team were subject to random web-based identification via standard electronic means (e.g., Centers for Medicare & Medicaid Services [CMS] Open Payments, ProPublica).

D. Patient Perspective

When developing a CPG, consideration should be given to patients’ perspectives and experiences, which often differ from those of providers.(90) Focus groups can be used to help collect qualitative data on patient perspectives and experiences. VA and DOD Leadership arranged a virtual Patient Focus Group on June 27, 2025. The focus group aimed to gain insights into the perspectives of adult patients with OA of the hip or knee who have received care in the VA and DOD healthcare systems and incorporated these insights into the CPG, as appropriate. Topics discussed included various interventions they have used, care delivery preferences and values, treatment challenges, other strategies or resources they have employed to manage OA, and the impact of OA on their lives.

The Patient Focus Group was comprised of a convenience sample of seven participants, which included two men and five women. Participants predominantly received care from the VA and DOD, with some individuals receiving primary care or physical therapy from a civilian provider due to scheduling or staffing constraints. The length of treatment ranged widely from as recent as 1 year to 20 years or more. The participants were primarily younger, ranging from 42-81 years old. Many of the participants were retired military personnel or Veterans but some were actively employed in other fields. The Work Group acknowledges that this convenience sample is not representative of all individuals who have undergone management of OA within the VA and DOD healthcare systems, and thus, findings are not generalizable and do not comprise evidence. For more information on the patient focus group methods and findings, see Appendix E. Patient Focus Group participants were provided with the opportunity to review the final draft of this CPG and share additional feedback.

E. External Peer Review

The Work Group drafted, reviewed, and edited this CPG using an iterative process. For more information, see Drafting and Finalizing the Guideline. Once the Work Group members completed a near-final draft, they identified individuals from VA and DOD healthcare systems and external organizations generally viewed as experts in their respective fields. The draft was sent to those experts for a 14-business-day review and comment period. The Work Group considered all feedback from the peer reviewers and modified the CPG where justified, in accordance with the evidence. Detailed information on the external peer review may be provided by the VA Office of Quality and Patient Safety.

F. Implementation

This CPG and algorithm are designed for adaptation by individual health care providers with respect to unique patient considerations and preferences, local needs, and resources. The algorithm serves as a tool to prompt providers to consider key decision points in the care of patients who have OA and would benefit from non-surgical management. The Work Group will submit suggested performance metrics for VA and DOD to use when assessing the implementation of this CPG. Robust implementation is identified in VA and DOD internal implementation plans and policies. Additionally, implementation will entail wide dissemination through publication in the medical literature, online access to the final CPG, educational programs, and ideally, electronic medical record programming in the form of clinical decision support tools at the point-of-care.

VII. Approach to Care in the Department of Veterans Affairs and the Department of Defense

A. Patient-Centered Care

VA and DOD encourage providers to be sensitive to demographic, cultural, and other differences that affect patients’ values, needs, and preferences, aimed at treating the condition while also optimizing the individual’s overall health and well-being. Regardless of the care setting, all patients should have access to individualized evidence-based care. Patient-centered care can decrease patient anxiety, increase trust in providers, and improve treatment adherence.(96,97) A whole health approach (https:/www.va.gov/wholehealth/) empowers and equips individuals to meet their personal health and well-being goals. Clear communication is essential and should be supported by evidence-based information tailored to each patient’s needs. Guideline recommendations should be applied in a holistic approach to care that is patient-centered, culturally appropriate, and available to people with limited literacy skills and physical, sensory, or learning disabilities. The focus is using an individual’s risk factors and event history to guide the various treatment and management strategies among patients with OA of the hip and/or knee.

B. Shared Decision-Making

This CPG encourages providers to practice shared decision-making, a process in which providers, patients, and patient care partners (e.g., family, friends, caregivers) consider clinical evidence of benefits and risks as well as patient values and preferences to make decisions regarding the patient’s treatment.(98) Shared decision-making is emphasized in “Crossing the Quality Chasm”, an Institute of Medicine, now NAM, report in 2001 (99) and is a core component of a patient- centered, whole health approach. Providers must be adept at presenting information to their patients regarding individual treatments, expected risks, possible outcomes, and levels and/or settings of care, especially where patient heterogeneity in weighing risks and benefits might exist. The VA and DOD have embraced shared decision-making. Providers are encouraged to use shared decision-making to individualize treatment goals and plans based on patient capabilities, needs, values, and preferences.

C. Patients with Co-Occurring Conditions

Co-occurring conditions can modify the degree of risk, impact diagnosis, influence patient and provider treatment priorities and clinical decisions, and affect the overall approach to OA management. Many Veterans, Active-Duty Service Members, and their families have one or more co-occurring conditions. Because OA is often accompanied by co-occurring conditions, collaborative management with other care providers is often best. Some co-occurring conditions may require early specialist consultation to determine necessary changes in treatment or establish a common understanding of how care should be coordinated.

VA/DOD Clinical Practice Guideline for the Non-Surgical Management of Hip & Knee Osteoarthritis

VIII. Algorithm

This CPG’s algorithm is designed to facilitate understanding of the clinical pathway and decision- making process used in the management of OA of the hip and knee. The algorithm format represents a simplified flow of the management of patients with OA and who would benefit from non-surgical management, helping foster efficient decision-making by providers. It includes:

• An ordered sequence of steps of care;
• Recommended observations and examinations;
• Decisions to be considered; and
• Actions to be taken.

The algorithm is a step-by-step decision tree. Standardized symbols are used to display each step, and arrows connect the numbered boxes indicating the order in which the steps should be followed.(100) Sidebars provide more detailed information to assist in defining and interpreting elements in the boxes.

Module A. Management and Treatment of Osteoarthritis of the Hip and/or the Knee

Algorithm or figure on page 20 of the original PDF is not reproduced here — see the original document (text descriptions of the algorithms are in the appendix, if provided).

* See the VA/DOD Clinical Practice Guidelines for the Management of Adult Overweight and Obesity. Available at: https://www.healthquality.va.gov/guidelines/CD/obesity

**Consider early referral to physical therapy based on pain severity, functional limitations, and patient preferences † Because of safety concerns (e.g., hepatotoxicity), the lowest clinically effective dose should be used; in addition, a maximum of 4 g/day should never be exceeded ‡ Consider adding a PPI or misoprostol in patients at risk for UGI events who require treatment with NSAIDs (including COX-2); and should generally be avoided in patients with or at risk for CVD, CKD, and in those patients at risk for serious UGI toxicity Assessment of renal function should occur and NSAIDs (including COX-2) should be avoided in patients with eGFR <30 ml/min/1.73 m² Abbreviations: CKD: chronic kidney disease; COX-2: cyclooxygenase-2; CPG: Clinical Practice Guideline; CVD: cardiovascular disease; DOD: Department of Defense; eGFR: estimated glomerular filtration rate; ml/min/1.73 m²: milliliter per minute per 1.73 meters squared (measure of GFR); NSAIDs: non-steroidal anti- inflammatory drugs; OA: osteoarthritis; PPI: proton-pump inhibitor; UGI: upper gastrointestinal; VA: Department of Veterans Affairs

*CSI should be avoided for the three months preceding joint replacement surgery; CSI for the hip should be image-guided Abbreviations: CSI: corticosteroid injection; OA: osteoarthritis

IX. Recommendations

The evidence-based clinical practice recommendations listed in the table below were developed using a systematic approach considering four domains as per the GRADE approach (see Summary of Guideline Development Methodology). These domains include confidence in the quality of the evidence, balance of desirable and undesirable outcomes (i.e., benefits and harms), patient values and preferences, and other implications (e.g., resource use, equity, acceptability).

Table 4. Evidence-Based Clinical Practice Recommendations with Strength and Category While some of these recommendations may clearly be an element in a particular phase of care, others may require consideration throughout the continuum of care.

a For additional information, please refer to Determining Recommendation Strength and Direction b For additional information, please refer to Recommendation Categorization * See the VA/DOD Clinical Practice Guideline for the Management of Adult Overweight and Obesity. Available at: https://www.healthquality.va.gov/guidelines/CD/obesity/ ** See the VA/DOD Clinical Practice Guideline for the Use of Opioids in the Management of Chronic Pain. Available at: https://www.healthquality.va.gov/guidelines/pain/cot/

A. Diagnosis

Recommendation

1. For the diagnosis of osteoarthritis of the hip and knee, we suggest against magnetic resonance imaging, computed tomography, and ultrasound. (Weak against | Reviewed, New-replaced)

Discussion

The Work Group reviewed the evidence which evaluated the efficacy of magnetic resonance imaging (MRI), computed tomography (CT) and ultrasound (US) in the diagnosis of OA of hip and knee.

Radiologic exams are frequently ordered in the primary care setting to make or confirm the diagnosis of OA of the hip and/or knee. Kellgren-Lawrence (KL) grades of OA have been the gold standard of using plain X-Rays to confirm the presence on OA. Advanced imaging techniques include MRI, CT scans and US and several studies have been done to evaluate the role of these studies in the diagnosis of OA.(101,102)

MRI can show articular cartilage loss, joint effusions, injury to intra- and extra-articular soft tissue structures and evaluate the presence of bone marrow edema consistent with OA. The reviewed evidence from the previous Work Group included two diagnostic cohort studies by Xu et al. (2013) and Segal et al. (2015) that did not show a clear benefit of MRI over plain radiographs for the diagnosis of OA of the hip and/or knee.(101,102) However, a study by Menashe et al. (2012) did show a benefit only in ruling out OA, rather than diagnosing it.(103) Because Menashe et al. (2012)(103) did not meet the inclusion criteria for this CPG’s systematic evidence review, it was not considered in determining the strength of this recommendation and the previous Work Group concluded MRI should not be routinely used in the diagnosis or workup of OA.

The Work Group reviewed the current literature and will discuss the findings on the accuracy of MRI, CT and US vs X-ray for the diagnosis of OA. The strength of evidence of three studies was low, and one was moderate. We did not identify any new studies related to HOA.

Muñoz-García, et al. (2020) looked at the accuracy of MRI vs X-ray in the diagnosis of KOA using arthroscopy as the reference standard. MRI alone compared to X-ray showed a greater specificity (SP) (88.6% vs 60%) but a lower sensitivity (SN) (70.8% vs 75%) in diagnosing OA. When evaluating the degree of OA, they found that MRI underestimated the degree of early OA when compared to arthroscopy and demonstrated a large variability in the KL grades of MRI vs arthroscopy. We did not identify any studies related to HOA. The Muñoz-García et al. (2020) study evaluated MRI compared to arthroscopy as a reference standard. The study found there was no added benefit of weight-bearing radiographs to the MRI findings, however, the evidence demonstrated a large variability in severity of OA on MRI versus arthroscopy. MRI and X-ray were more predictive of diagnosis more advanced cases of OA and there was no benefit to combine both studies in the diagnosis of OA.(104)

There is some variability in patient expectations regarding the use of MRI for hip and knee OA. Some patients inaccurately believe that MRI is better than plain radiographs and, as such, may request an MRI in the clinical setting. They also may feel that MRI is safer due to decreased radiation. The Work Group recognizes this can pose difficult clinical scenarios; however, providers should feel comfortable educating patients on the lack of superiority of MRI over radiographs from a diagnostic standpoint. Additionally, the overall burdens associated with MRI (e.g., increased resource use, cost, time, and logistic difficulty), far outweigh those associated with weight-bearing radiographs. Moreover, while there is minimal physical harm associated with MRI testing, sometimes results can mislead patients and providers as to proper diagnosis and treatment. Some orthopedic surgeons may request an MRI for surgical planning; however, this applies to a minority of patients and should be left to surgeon discretion following surgical consultation.

In the evaluation of CT for KOA Segal et al. (2021)(105) compared weight bearing CTs to lateral radiographs using MRI as a reference standard. This study evaluated patellar femoral arthritis and showed a weight bearing CT had a greater SN (85%-97% vs 48%-57%) for the diagnosis of KOA compared to a lateral X-ray but a lower SP using an axial weight bearing CT for detecting lateral full-thickness cartilage loss (32% vs 68%) in the diagnosis of OA. The CT scan when compared to an X-ray is costly, requires more resources, greater exposure to radiation and can be a time burden to patients and providers, and possible increased pain to patients due to prolonged standing for weight bearing CT. The authors commented in their discussion that future studies would compare weight bearing CT to the gold standard of a Skyline view.

Two US studies, Brom et al. (2020)(106) and Yates et al. (2025)(107) were evaluated for their ability to detect OA of the knee. Currently there is no defined US protocol to detect OA, so Yates et al. (2025)(107) proposed a US based protocol for OA evaluation of radiographic KOA. They demonstrated that an experienced ultrasonographer could detect osteophytes and thinning of the femoral cartilage associated with the detection of OA. Brom et al. (2020)(106) reported US was able to detect OA with a 95% SN for the detection of femoral cartilage thinning or presence of osteophytes in knee OA and 94% SP when combining the loss of femoral cartilage and presence of osteophytes. Most of the findings were in patients with KL 3 grades and they noted an experienced ultrasonographer may be able to detect earlier stages of OA.

Although US demonstrated excellent SN and adequate SP in the detection of KOA it was still limited in early onset arthritis and limitations were present secondary to body habitus, user variability, acoustic windows which could not detect the physiological changes associated with weight bearing. The benefit of US is that it may be readily available in specialty clinics and is a non-painful diagnostic tool. The harm is that it is not always available in primary care clinics and risks variable results due to variability in user expertise.

The Work Group systematically reviewed evidence related to this recommendation.(101- 104,106,107) There were two new modalities added for the diagnosis of OA of the knee. Therefore, it was categorized as Reviewed, New-replaced. The Work Group’s confidence in the quality of evidence was Low. Advanced imaging has improved in the detection of OA, but the reviewed literature did not demonstrate the superiority of MRI, CT, and US to plain, weight- bearing X-rays in the diagnosis of OA of the knee. Many patients believe MRI is superior to any other imaging and may detect early OA, but the SN was poor compared to arthroscopic findings in the detection of OA. The weight bearing CT was better than a lateral knee X-ray for diagnosis of patellar femoral arthritis but not compared to a Skyline View X-ray which is the current gold standard. US did show promise in the detection of OA but is still developing the protocols needed to detect OA. US is not always readily available and does require an experienced ultrasonographer. The harms, included increased cost, resource use, and time burden for the patients and providers, increased pain due to prolonged standing for weight bearing and CT, and radiation for CT and MRI overall the harms outweighed the lack of evidence-based benefits. Thus, the Work Group decided upon a Weak against recommendation.

B. Lifestyle-Based Interventions

Recommendation

2. In individuals with osteoarthritis of the knee and co-occurring obesity/overweight*, we recommend weight loss to improve osteoarthritis symptoms and outcomes. (see VA/DOD Management of Adult Overweight and Obesity CPG) (Strong for | Reviewed, New-added)

3. In individuals with osteoarthritis of the hip and co-occurring obesity/overweight*, we suggest weight loss to improve osteoarthritis symptoms and outcomes. (see VA/DOD Management of Adult Overweight and Obesity CPG) (Weak for | Reviewed, New-added)

Discussion

Obesity is defined as a chronic, relapsing, multifactorial disease characterized by abnormal or excessive adipose tissue accumulation that impairs health and increases the risk of comorbidities and premature mortality.

The causes of obesity are multifactorial and include genetic susceptibility, environmental and social determinants, behavioral patterns, and physiological dysregulation of multiple systems.

Overweight is often viewed as a precursor or a less severe form of this same chronic condition.* Obesity is defined as a BMI of 30kg/m², and overweight is defined as between 25-29.9kg/m². In the DOD, normal BMI is defined between 19-27.5kg/m² to account for characteristic enhanced musculature in Active-Duty populations compared to their civilian counterparts. BMI is the most used screening tool for overweight and obesity and is calculated as weight in kilograms divided by height in meters squared (kg/m²); it is widely utilized due to its low cost, easy to use, scalable, and convenience.•◘○* While commonly used, BMI is not without its faults and does not have a component in its calculation to differentiate lean tissue mass, including bone, blood, and essential fat mass, from other adipose tissue.

Throughout the review of evidence, improved outcomes on principle areas of clinical importance were more consistently noted in patients with KOA than with HOA. The strength of evidence of KOA outcomes was mostly moderate, compared to the low/very low quality of evidence for HOA. Meta-analysis showed that the greater the weight loss, the better the clinical function, reduced joint stiffness, and pain reduction. Dose dependent outcomes were regularly observed across 12 weight loss modalities ranging from cognitive behavioral therapy (CBT) to bariatric surgery.(108) Across 18 studies, each decrement of 1% in weight affected an average decrement of about 2% in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function, with 13 studies corroborating the same dose effect for WOMAC stiffness.(108)

* See the VA/DOD Clinical Practice Guideline for the Management of Adult Overweight and Obesity. Available at: https://www.healthquality.va.gov/guidelines/CD/obesity/

The same response was also noted for WOMAC pain over the analysis of 22 studies.(108) Important risk reduction was noted for knee surgery and inversely associated with weight loss percentage. Each reduction in unit BMI from baseline was associated with a 2-3% decrease in knee replacement,(109,110) with individuals losing >7.5% demonstrating the most significant reduction in risk for knee replacement.(110)

Meaningful, clinically significant HOA outcomes were less frequently observed across continuous measures of weight loss, and instead, were more significantly concentrated on weight loss that categorically occurred at >10%. Dose dependent responses were also observed across the Hip Disability and Osteoarthritis Outcome Score (HOOS) pain, range of motion, and QoL such that a 1% reduction in weight loss was associated with 0.54, 0.43, and 0.67 unit reductions in HOOS subscales, respectively.(111) Overall, inconclusive evidence was synthesized for total hip replacement with reduced risk for surgery only being identified with >5% weight gain (110) and no difference in risk for surgery from weight stable groups across all weight loss cohorts.(109,110)

The Work Group did note some significant limitations to generalizability regarding participants and methods. While over half the studies included in network meta-analyses (NMA) were RCTs, examining the studies included from Panunzi et al. (2021)(108) constituted a population of 75% women. Despite the generally recognized higher prevalence and incidence of OA in women, the VA/DOD populations are predominantly male, and outcomes may not generalize to Veterans and military Service Members.

Similarly, the inclusion of exercise in many weight loss modalities examined in Panunzi et al. (2021)(108) may conflate some of the improvements noted from weight loss with potential improvements from benefits more exclusively observed and reported from physical activity alone or in combination with other therapies.

Throughout the body of evidence included for the review of weight loss on KOA and HOA outcomes, an overwhelming consensus favoring benefits over harm was upheld. In patients with obesity/overweight, weight loss as an outcome is consistently regarded as appropriate, safe, and advantageous for many health outcomes. These benefits include improved function, stiffness, pain, and risk reduction for surgery. Modalities of weight loss such as pharmacotherapy, bariatric surgery, and specific exercise/dietary interventions accompany significant risk. Specific weight loss modalities and safety were not included within the scope of the evidence at this time.

Some variation in patient preferences may exist regarding weight loss. Overweight, and certainly obese patients, are likely to have had some form of care or conversation with their primary provider before beginning the OA clinical pathway. Failure or inability to reduce weight may be negatively associated with self-efficacy or partially negate social determinants of health (SDOH) beyond the patient’s capacity to address. Great care must be rendered navigating these complex intersectionalities to preserve provider-patient trust and maintain quality of care. Furthermore, some patients may experience disproportionate rates of adequate food access, education, economic stability, and urbanization. The culmination of these factors can greatly impact access to care making some weight loss modalities, like bariatric surgery, unfeasible for some.

Modality aside, there are also patients that may require more individualized care for discussions of weight loss such as elderly patients who are diagnosed with sarcopenia or Active-Duty military who have a high BMI with significant musculature.

The Work Group systematically reviewed evidence related to these recommendations.(108-111) The strength and quality of evidence was consistently higher for outcomes of interest including WOMAC and HOOS function, pain, stiffness and QoL related to KOA over HOA.(109,110) Within KOA studies, results consistently upheld 1% changes in body weight with 2% improvements on WOMAC function, stiffness, and pain scores.(108) Weight loss was also well represented as a protective measure against total knee replacement, but the evidence for hip replacement was largely insufficient.(109,110) Therefore, it is categorized as Reviewed, New-added. The Work Group’s confidence in the quality of the evidence for the hip and knee was Moderate. The body of evidence had some limitations including the generalizability of the study's findings, particularly for VA/DOD populations. The research, which drew heavily from a meta-analysis where 75% of participants were female. Furthermore, the common inclusion of exercise within the weight loss modalities studied makes it difficult to distinguish the benefits of weight loss from those of physical activity, possibly conflating the results. The benefits of weight loss were consistently viewed as safe and effective and significantly outweighed the potential harm of select weight loss modalities that were beyond the scope of the Work Group to evaluate at this time. Patient values and preferences had some variation because of the feasibility, resource availability for some modalities like surgery, and appropriateness due to considerations like enhanced musculature in Active-Duty populations and presence of sarcopenia in older patients. Thus, the Work Group decided upon a Strong for recommendation for KOA and a Weak for recommendation for HOA.

Recommendation

4. For the self-management of osteoarthritis of the knee, we suggest tailored patient education and physical activity. (Weak for | Reviewed, New-replaced)

Discussion

Self-management is the active engagement of individual patients in daily tasks or activities that aim to improve their QoL and long-term management of the health condition.(112) Providing education and self-management support which could help enable patients to adopt self-directed behaviors which are known to promote joint health are likely to be helpful (see Appendix L for education content).(113) Patients implement these structured activity strategies on their own though most care plans include initial patient education and additional support to be successfully implemented. A growing body of evidence indicates that telehealth supported exercise programs may be a practical strategy to reduce pain and improve functional outcomes in KOA.

Xiang et al. (2024)(114) performed a SR with 11 RCTs comparing telehealth supported exercise vs inactive controls in patients with KOA. The results favored the telehealth-supported exercise programs for improvement in function and reductions in pain. The included studies demonstrated considerable risk for bias, heterogeneous interventions, and statistical analyses of outcomes showing a wide confidence interval. The strength of evidence was therefore rated as low. Similarly, in another SR containing 5 RCTs (115) telehealth-based exercise interventions delivered by web or smart phone were effective in improving pain and physical function in patients with KOA, comparable to traditional face to face exercise treatment and better than usual care or an inactive control. The included studies demonstrated limitations in study quality with small sample sizes and wide confidence intervals. The strength of the evidence was therefore rated as low.

Three additional RCTs (116-118) investigated web or app-based applications with reminders promoting program adherence. Each demonstrated improvements in function in patients with KOA when compared to usual care or an inactive control. One small RCT (119) demonstrated no difference in function between home-based circuit training and a no exercise control group. However, findings in this study favored the home-based intervention over control for reduction in pain.

Modes of telehealth interventions varied across the studies included in the evidence base, though meaningful differences were more commonly observed in interventions with a structured program (education, patient logging, continual access to program and implementation guidelines) compared to programs consisting of only telephone contact and reminders. Methods included delivery by telephone, mobile app, internet, wearable device, or applications combined with wearable devices. There were no adverse events or harms reported.

The Work Group also considered patient values and preferences for self-managed physical activity, feeling that there would be some variation in patient values and preferences toward telehealth interventions. Access to technology and the ability to adequately navigate the internet and mobile applications may also vary among patients, and comfort with technology use

The Work Group systematically reviewed evidence related to this recommendation.(112-119) Therefore, it is categorized as Reviewed, New-replaced. The evidence found treatment with certain self-directed exercise interventions to improve function, pain, and QoL when compared to usual care/standard of care. The Work Group’s confidence in the quality of evidence was Low. The body of evidence had limitations in the methodological quality of the included RCTs, indirectness due to some RCTs included in the SRs not meeting the minimum follow-up, and imprecision due to wide confidence intervals and limited information on specific components of the exercises. The benefits of improved pain, QoL (physical), physical function, and mobility in patients with KOA outweighed the potential harm of adverse events, which were negligible. For the various types of self-managed activity programs, feasibility will depend on the equipment, technology, and education required. Overall, patient values, preferences, adherence, and self- efficacy regarding participation in exercise programs may vary. Thus, the Work Group decided upon a Weak for recommendation.

C. Physical Therapy

Recommendation

5. For osteoarthritis of the hip and knee, we suggest a structured physical therapy program.

(Weak for | Reviewed, Amended)

Discussion

Physical therapy is a structured rehabilitation intervention that focuses on optimizing movement and physical function in patients with a variety of conditions including musculoskeletal conditions such as hip or knee osteoarthritis. For knee and hip OA, physical therapists frequently combine progressive exercise, manual therapy and gait/movement retraining to address pain and functional deficits. Physical therapists also provide education related to pain, lifestyle and activity modifications. Extensive literature exists to support the use of physical therapy as a core treatment in the comprehensive management of patients with OA of the hip or knee. For example, a RCT by Deyle et al. (2020) compared physical therapy to glucocorticoid injections in a military health system and results favored the physical therapy group on both primary and secondary outcome measures at one year.(81) Since this study was not included in this CPG’s systematic evidence review, it did not impact the strength of this recommendation. An individualized physical therapy management plan can reduce pain and improve function in patients with hip or knee OA and, therefore, augment medical and pharmacologic approaches.(120-122) Physical therapists may utilize both manual physical therapy treatments and prescribed exercises in the treatment of knee and hip OA. Manual therapy treatments utilize hands-on techniques such as soft tissue mobilization, joint manipulation, and joint mobilization. Physical therapists also provide patients with education related to pain, lifestyle, and activity modifications. In addition to exercise and manual therapy, physical therapists may incorporate adjunctive modalities.

In patients with features suggestive of nociplastic or centrally mediated pain, physical therapy management may also incorporate biopsychosocial interventions aimed at addressing psychological and behavioral contributors to pain. As outlined in Appendix I, these approaches may include strategies consistent with CBT, Acceptance and Commitment Therapy (ACT), Pain Reprocessing Therapy (PRT), and Cognitive Functional Therapy (CFT). Within some care settings, including interdisciplinary pain programs, physical therapists may play a primary role in delivering or reinforcing these interventions as part of a comprehensive, multimodal treatment approach.

Knee Osteoarthritis

A SR by Anwer et al. (2018) examined the effects of manual therapy in patients with KOA.(121) They compared manual therapy alone or manual therapy in combination with exercise-to- exercise therapy alone or control. The SR consisted of 11 RCTs (n=494). Their review indicated short-term benefit of exercise therapy with manual therapy compared to exercise alone and a stronger effect on pain relief from manual therapy alone compared to exercise alone in short-term follow-up. The Work Group noted serious limitations in the results due to considerable heterogeneity of the manual interventions and the quality of some of the individual trials. Manual therapy interventions included Maitland mobilizations, mobilizations with movement, soft tissue mobilization, myofascial techniques, and high velocity low amplitude thrust techniques to other lower extremity joints. Only four of the 11 trials were a Physiotherapy Evidence Database (PEDro) grade of six or higher with the remaining scoring below six, indicating overall low quality. Two RCTs directly compared manual therapy plus exercise to exercise alone in KOA.(123,124) Abbott et al. (2015) performed a four-arm parallel group factorial RCT in 75 patients and found that exercise with booster sessions and exercise plus manual therapy produced the strongest improvements in WOMAC scores and sit-to-stand tests at one year compared to exercise alone, with favorable pain reduction in the manual therapy group.(123) Fitzgerald et al. (2016) conducted a similar four-arm RCT in 300 patients and found no differences between groups at one year on WOMAC or performance-based measures; however, secondary analysis suggested short-term benefit of manual therapy and booster sessions, with increased odds of pain relief at one year.(124) Overall, physical therapy approaches utilizing manual therapy with or without exercise appear to show positive effects on pain and function in KOA at both three-month and one-year follow-up.

Hip Osteoarthritis

Beumer et al. (2016) performed a SR and meta-analysis of exercise and manual therapy on pain with HOA.(120) The SR included 19 RCTs though only four studies directly compared manual therapy and exercise vs exercise alone vs control. The results indicated a short-term benefit for pain relief and function when comparing aquatic and land-based exercise to control. However, the findings did not demonstrate additional benefit of manual therapy, with or without exercise, compared to exercise therapy alone or a minimal control in short-term comparisons. There was considerable heterogeneity among trials in terms of size and methodology, and the authors emphasized the need for future well-designed trials evaluating manual therapy and exercise in HOA. The effect of manual therapy in HOA therefore remains less clear compared to KOA. Shared decision-making between the physical therapist and patient is important when considering manual therapy interventions, and clinicians must also weigh the economic burden associated with various physical therapy approaches, including lost wages, transportation costs, and co-pays.

This is a Reviewed, Amended recommendation and no new evidence was reviewed. The Work Group issued an addendum focused on refinement of the recommendation wording. The strength of evidence remains unchanged from the prior recommendation. The Work Group’s confidence in the quality of evidence continues to be low, consistent with previously identified limitations including small sample sizes, confounding in analyses, and attrition of participants. Despite these limitations, the Work Group determined that the benefits of exercise-based physical therapy, including improvements in pain, function, and QoL, outweigh the potential harms. Physical therapy is generally safe and associated with minimal risk of injury. Identified harms include the burden of time, effort, and adherence, potential financial cost, and the possibility of transient soreness or temporary increases in pain. Higher-intensity exercise modalities, particularly eccentric loading, may carry a greater risk of muscle injury, though serious adverse events (SAEs) remain rare.

Patient values and preferences are largely aligned with prior recommendations, with many patients favoring non-pharmacologic approaches. Variation exists, as some patients hold erroneous beliefs that physical therapy or strengthening exercises may worsen OA, while others perceive therapy as burdensome due to visit frequency. Preferences may also vary by delivery mode as discussed in the next recommendation. From a resource-use perspective, exercise- based therapy is relatively low cost, though certain modalities such as aquatic interventions require access to specialized locations. Overall acceptability is high, feasibility is supported by the availability of multiple delivery formats (including in-person and remote options), and subgroup considerations suggest that some patients may derive greater benefit than others depending on individual factors.

The Work Group systematically reviewed evidence related to this recommendation from the existing CPG evidence base and no new evidence was identified or reviewed for this update. Therefore, it is categorized as Reviewed, Amended. The Work Group’s confidence in the quality of the evidence was Low. The body of evidence had some limitations including small sample sizes, confounding in analyses, and attrition of participants, as reported in prior SRs and randomized trials evaluating exercise-based interventions for OA.(125,126) The benefits of exercise-based physical therapy, including improvements in pain, physical function, and QoL outweighed the potential harms which were small and primarily related to treatment burden, cost, and transient symptom exacerbation. Patient values and preferences varied somewhat because many patients favor non-pharmacologic approaches, while others perceive physical therapy as burdensome due to visit frequency, cost, or concern that exercise may worsen OA Other considerations included generally low resource use, high acceptability, broad feasibility across multiple delivery formats (including in-person and remote options), and a low incidence of adverse events, with higher-intensity exercise modalities such as eccentric loading carrying a slightly increased but still rare risk of muscle injury.(127) Thus, the Work Group decided upon a Weak for recommendation.

Recommendation

6. For osteoarthritis of the hip and knee, there is insufficient evidence to recommend for or against a specific type or mode of delivery of a structured physical therapy program over another. (Neither for nor against | Reviewed, New-added) Discussion

The Work Group determined there is insufficient evidence to recommend for or against one specific type of exercise-based physical therapy program or one mode of delivery over another for individuals with OA of the hip or knee. The available evidence primarily evaluates exercise interventions rather than the broader components of physical therapy (e.g., manual therapy, modalities, or other adjunctive treatments), and therefore this recommendation is focused on exercise program characteristics rather than the full scope of physical therapy practice. Physical therapy that includes structured exercise is widely supported as a key part of OA management. However, patients often have questions about which type of exercise program works best. Programs can vary by setting (land-based vs. aquatic), intensity (high vs. low), focus (general strengthening vs. motor control), and delivery method (in-person, home-based, or telehealth- supported). After reviewing the available research, the Work Group found that there is not enough consistent evidence to recommend one specific type of exercise program or delivery method over another. The current evidence does not show clear, reliable superiority of any single exercise approach or format across important outcomes such as pain and function.

Multiple recent SRs evaluating a wide range of exercise modalities and delivery formats, including land-based exercise, resistance training, aerobic exercise, aquatic therapy, motor control-focused programs, and technology- or telehealth-supported intervention, generally found similar improvements in pain, function, and QoL. No modality consistently outperformed others.(128-132)

Mo et al. (2023) conducted a SR and NMA of 39 RCTs looking at exercise therapies for KOA, and found that multiple exercise modalities, including aerobic exercise, resistance training, yoga, stationary cycling, and traditional exercise, were effective in improving pain, stiffness, physical function, and QoL.(128) In treatment rankings, yoga and aerobic exercise tended to rank higher for pain and stiffness reduction, resistance training ranked higher for physical function, and mind- body or mixed exercise programs ranked favorably for QoL, though the authors emphasized that differences were based largely on indirect comparisons and did not demonstrate consistent superiority of one modality across all outcomes.

Xu et al. (2023) conducted a SR and meta-analysis of 11 RCTs evaluating aquatic exercise in people with KOA and found that aquatic exercise produced significant short-term improvements in pain, stiffness, and physical function compared with no exercise.(129) However, when compared with land-based exercise, there were no significant differences between aquatic and land-based exercise in pain, stiffness, or physical function, and no SAEs were reported.

Zhai et al. (2025)(131) conducted a SR and meta-analysis of 9 RCTs evaluating high-intensity training in patients with KOA, finding that high-intensity exercise significantly improved knee flexion strength, leg press strength, Knee Injury and Osteoarthritis Outcome Score (KOOS) symptoms, and KOOS QoL compared with control interventions.(131) However, it had no significant effect on overall pain (WOMAC/KOOS pain), 6-minute walk test (6MWT), knee extension strength, stair climbing, or timed up-and-go (TUG) performance.

Lastly, evidence from systematic reviews and a non-inferiority RCT indicates that digital and mobile health-supported exercise or rehabilitation interventions produce improvements in pain and physical function that are comparable to in-person physiotherapy or usual care, with no consistent evidence that digital delivery is superior to traditional approaches.(132-134)

The Work Group also considered patient values and preferences as Veterans and Service Members consistently express a preference for non-pharmacologic, active treatments. Variability in exercise type, intensity, and delivery modality is particularly valued, given variable duty demands and/or access to care. From a resource perspective, exercise-based physical therapy and self-management interventions are relatively low cost and scalable, especially when delivered through home-based or telehealth-supported formats. Acceptability of these interventions is high across clinical settings, and feasibility is supported by multiple delivery options. Subgroup considerations include the need to individualize programs for those with high BMI, chronic pain, or prior musculoskeletal injury, as well as for older Veterans with mobility limitations, where lower- impact or progressive programs may be preferred. No evidence outside the scope of the SR was used to inform the strength of this recommendation.

The Work Group systematically reviewed evidence related to this recommendation, including multiple SRs and RCTs evaluating different types of exercise, exercise intensity, and modes of delivery for physical therapy in patients with OA of the hip and knee.(128-134) Therefore, this recommendation is categorized as Reviewed, New Added. The Work Group’s confidence in the quality of the evidence was Low, as the body of evidence had several limitations, including heterogeneity in exercise interventions and outcome measures, small sample sizes in individual trials, and short follow-up durations in some studies. Across the evidence base, no single exercise modality (e.g., resistance training, aerobic exercise, aquatic therapy, motor control training), intensity, or mode of delivery (e.g., supervised, home-based, or digital/telehealth-supported) demonstrated consistent superiority over others for improving pain, function, or QoL. The benefits of offering physical therapy and exercise-based interventions, including improvements in pain, function, and overall physical performance, outweighed the potential harms, which were generally small and consisted primarily of transient musculoskeletal discomfort or symptom exacerbation, with SAEs being rare. Patient values and preferences varied somewhat, as most patients valued non-pharmacologic, active treatments but differed in preferred exercise type, intensity, supervision level, and delivery format based on lifestyle, access, and tolerance for discomfort. Considering the favorable balance of benefits to harms, generally similar patient values with some variation, and low certainty of evidence without clear superiority of one approach, the Work Group decided upon a Neither for nor against recommendation.

D. Devices

Recommendation

7. In select patients with osteoarthritis of the knee, we suggest bracing.

(Weak for | Reviewed, New-replaced)

Discussion

Soft braces and valgus knee braces improve pain and physical function in the knee joint in individuals with KOA.(135-137) Soft braces are elastic non-adhesive orthoses which do not provide realignment of the knee.(136) Soft braces are thought to improve proprioception via stimulation of cutaneous mechanoreceptors, additionally they exert a mild compression effect and are thought to improve the patient’s sense of joint stability leading to greater confidence in the knee joint.(136) Valgus braces are hinge braces with a leverage system designed to apply a corrective force to redistribute load away from the medial compartment, additionally these braces are also thought to improve joint stability and proprioception.(135)

The previous evidence synthesis review identified one SR on soft braces by Cudejko et al. (2018) which showed a statistically significant difference favoring soft braces in three RCTs compared to a usual care control group.(136) The soft brace had a moderate effect on decreasing pain up to 24 weeks (standard mean difference [SMD] 0.61) and a small to moderate effect on physical function up to 24 weeks (SMD 0.39). The strength of this evidence was rated as low with potential for bias related to blinding in some of the studies and the impossibility of blinding participants in brace trials. Additionally, there was insufficient evidence to recommend one specific soft brace over another. The choice of usual care as a control group in RCTs has potential limitations because of variability and inconsistency typically present in usual care across trials. No data for harms for soft brace were reported however the Work Group acknowledged potential downsides including slipping, discomfort related to excessive heat retention, and constraining/swelling if brace is poorly fitted. Overall, the Work Group felt these harms to be minor and likely infrequent compared to potential benefits.

The previous evidence synthesis review identified one meta-analysis on valgus braces by Moyer et al. (2015)(135) which found a statistically significant difference favoring valgus knee bracing for pain and function in patients with medial compartment KOA up to 52 weeks. The effect sizes were moderate for pain (SMD 0.56) and function (SMD 0.48) compared to the control group without orthosis use, but only a small statistically significant effect for pain (SMD 0.33) compared to a control group with a control orthosis.(135) Minor complications such as slipping, skin irritation and constraining or poor fit were common with estimates 1-22% while other complications such as swelling or blisters were infrequently reported as 3-4% event rate. Instructions varied considerably for brace use (i.e., how many days per week, how many hours per day and for what activities). Additionally, there was insufficient evidence to recommend one specific valgus brace over another. The strength of this evidence was rated as low with potential for bias related to blinding noted in some of the studies and the impossibility of blinding participants in brace trials. The current evidence synthesis review found one additional trial Gueugnon et al. (2021) comparing a specific valgus type brace (ODRA brace) to usual care up to 52 weeks. Statistically significant improvements in pain, function, and QoL were reported.(137) The quality was graded as very low due to concerns for imprecision and risk of bias. The strength of evidence for this study was rated as very low.

The Work Group also considered patient values and preferences indicating general acceptance for soft bracing whereas valgus bracing may elicit more variable preferences due to concerns regarding bulk and fit. Patient adherence/wear time with brace can be influenced by comfort, appearance, and ease of application. Military profiling may be needed for the use of braces in Active-Duty Service Members. Some patients may find braces more uncomfortable in hot weather or interfere with certain clothing. Braces are generally inexpensive though valgus braces carry higher cost compared to soft braces and frequently require fitting and potentially custom sizing to accommodate deformity. Braces do require some resource use as they need to be fitted properly, and valgus braces may require additional appointments to adjust the brace to ensure proper fit. All braces have potential for slipping and may need periodic readjustment throughout the day. Patients with reported gait instability may require additional consideration of ambulatory aid. Valgus braces are primarily used for patients with medial tibiofemoral compartment KOA and varus deformity. Soft braces are often recommended to improve proprioception and sense of joint instability. Hinge braces were not part of the evidence review though the Work Group noted that common indications for hinge brace include the presence of medial or lateral instability.

Some providers may be hesitant to prescribe a brace due to concerns of muscle atrophy or functional loss. However, a study by Yu et al. (2016)(138) which was within the SR by Cudejko et al. (2018)(136) found that instead of functional loss, within group comparisons showed improvement on TUG and 6MWT up to 52 weeks in the soft bracing group.(138) Additionally, a secondary analysis of a RCT by Callaghan et al. (2016)(139) on bracing in Patellofemoral Joint (PFJ) OA, although outside the scope of the evidence review, did not influence the strength of the recommendation and found that use of a brace improved quadriceps muscle maximal voluntary contraction at 6 weeks compared to no brace. The original RCT by Callaghan et al. (2015)(140) was within the SR by Cudejko et al. (2018) which the Work Group reviewed.(136) The Work Group is not aware of any direct studies measuring quadricep muscle atrophy with brace use however, the potential concern would be highest for braces which immobilize the knee rather than a functional brace which allows for normal function and muscle use.

The Work Group systematically reviewed evidence related to this recommendation.(135- 137) Therefore, it is categorized as Reviewed, New-replaced. The Work Group’s confidence in the quality of the evidence was Very low. The benefits of bracing to improve functional outcomes and pain slightly outweighed the potential harms which are very minor and relate to fit of the brace. The body of evidence had some limitations including small sample size, variability in comparators’, blinding, imprecision, heterogeneity between studies Moyer et al. (2015) and Cudejko et al. (2018).(135,136) Patient values and preferences may have some variation, with most patients likely agreeable to trialing a brace though some patients may have different views on use of a brace and overall adherence/wear time with brace is influenced by comfort, appearance, ease of application etc. Thus, the Work Group decided upon a Weak for recommendation.

Recommendation

8. For osteoarthritis of the knee, there is insufficient evidence to recommend for or against the use of orthopedic insoles. (Neither for nor Against | Reviewed, New-added)

Discussion

There is insufficient evidence to recommend for or against orthopedic insoles including motion control insoles, lateral wedge insoles, and biomechanical footwear for improvement of pain and function in KOA. Orthopedic insoles are typically designed to alter ground reaction forces to reduce biomechanical moments of the knee and adjust joint force distribution to improve comfort and support during walking. For example, lateral heel wedges have been proposed to limit medial compartment stress by reducing the knee adduction moment (varus moment).

Yu et al. (2021)(141) performed a SR with 10 RCTs comparing orthopedic insoles primarily lateral wedge insoles to a control insole (neutral or flat insoles). There were no significant differences shown for pain or function for orthopedic insoles compared to control insoles. Most studies within the SR had low numbers of patients in each treatment group and some studies did not adequately match for age and sex which increased heterogeneity across trials. Further heterogeneity was noted across trials with respect to controlling for severity of KOA and/or duration of symptoms and with respect to the variability of outcome measurements across trials. The strength of evidence was therefore rated as very low. Hsu et al. (2022)(142) performed a small RCT (n=25) which compared a lateral wedge insole to a neutral insole. No differences were noted between baseline and 20 weeks for within group comparisons for pain and self- reported function for the lateral wedge insole group. The strength of evidence for this study was graded as very low due to concerns around imprecision, sample size, and blinding. Ferreira et al. (2021)(143) performed a small RCT (n=38) comparing lateral wedge insoles to neutral insoles and found no difference for pain, self-reported function or QoL at 12 weeks. The strength of evidence for this study was graded as very low due to concerns around imprecision, sample size and blinding. Paterson et al. (2022)(144) performed a small RCT (n=40) comparing motion control shoes, designed to offload the lateral knee compartment, to neutral shoes. No differences were reported for pain, self-reported function, or QoL between the two groups up to 6 months. The strength of evidence was rated as low due to study size and imprecision. A RCT by Reichenbach et al. (2020) (n=220)(145) compared biomechanical footwear to a control footwear. The biomechanical footwear involved individually calibrated convex pods designed to adjust the center of pressure and alter low limb biomechanics and compartment pressure. There was a statistically significant difference up to 16 weeks favoring the biomechanical footwear group for pain and self-reported function compared to control. However, this was the only randomized study on this intervention reviewed by the Work Group, and the group also weighed concerns regarding the cost, required training, and resource demands associated with biomechanical footwear. While the results appear promising, further studies are needed to replicate the results. There are likely no major harms from insoles and minor adverse events (AEs) for insoles are not well reported across studies. Reichenbach et al. (2020) reported the most common minor AEs were musculoskeletal pain related (15%) in the knee, back, hip or foot.(145) The Work Group also acknowledges potential for discomfort occurring with lateral wedge insoles which likely increase with increasing angulation (143) and insoles may require a break in/adjustment period.

The Work Group also considered patient values and preferences for orthotics, feeling that there would be some variation in patient values and preference toward orthopedic insoles and that comfort is likely to significantly impact adherence and tolerability of insoles. Military profiling may be needed for the use of specialized orthotics in Active-Duty Service Members. Orthotics can range in cost and can vary in quality and ability to alter external knee adduction moment. All insoles require some resource use to ensure proper sizing and fit, and customized insoles can considerably increase the cost and resources demand. There is variability in the literature regarding application and wear time. There is potential for increased foot/ankle, hip/low back discomfort related to changing biomechanical variables associated with gait.

The Work Group systematically reviewed new evidence related to this recommendation.(141-145) Therefore, it is categorized as Reviewed, New-Added. The Work Group’s confidence in the quality of the evidence was Very low. The body of evidence had some limitations including significant heterogeneity across trials, small sample sizes, differences in interventions across trial. The benefits of orthotics on pain and function are inconsistent and appear to be balanced with the potential harms which are small related to increased musculoskeletal discomfort. Patient values and preferences are likely varied because patients sometimes discontinue use of insoles due to discomfort. Thus, the Work Group decided upon a Neither for nor Against recommendation.

Recommendation

9. For osteoarthritis of the knee, there is insufficient evidence to recommend for or against the use of transcutaneous electrical nerve stimulation. (Neither for nor Against | Reviewed, Not changed)

Discussion

Assessing electrostimulation devices was not a key question for the 2025 CPG update so no new evidence was addressed or included in the query protocol. Although there is interest in use of non-invasive and non-pharmacologic interventions for the management of OA-related pain, the Work Group during development of the KQs thought it unlikely that there would be new evidence of sufficient rigor to better inform providers (e.g. change to either for or against recommendation). However, the Work Group felt carrying the 2020 recommendation forward was important as some patients prefer non-pharmacologic management options. Based on the 2020 review, a SR by Chen et al. (2016) found that transcutaneous electrical nerve stimulation (TENS) use in OA of the knee had a statistically significant but not clinically meaningful difference in pain compared to control.(146) Chen et al. (2016) noted that for small studies, the largest effects of TENS occurred at a two-week follow-up, while larger studies indicated no difference between TENS and control, especially in long-term follow-up.(146) The included studies also failed to show any improvement in range of motion or TUG test compared to control. The included RCTs had small sample sizes with considerable heterogeneity and inconsistencies in their findings, which makes it difficult to reach definitive conclusions.

Cherian et al. (2015) compared 40 patients with TENS to a standard control group and found statistically significant improvement in pain (Visual Analog Scale [VAS]) at three months but no significant difference in functional measures between groups.(147) A RCT by Inal et al. (2015) compared sham, high-frequency TENS, and low frequency TENS for patients with knee OA.(148) Inal et al. (2015)(148) found similar reductions in pain at rest and pain with movement but no differences between groups at two or six weeks. Cherian et al. (2016) found, among 30 patients randomized into a TENS group and a control group, the improvement in the TUG test, timed stair- climb test (SCT), and 20-time step test at three months favored the TENS group.(149) However, there was no significant difference between groups for pain (VAS) at three months. Another RCT by Cherian et al. (2016) compared standard care and TENS for OA of the knee and found no difference in pain (VAS) or functional outcomes measured at one year.(150) All four RCTs were small and had significant study limitations including limited description of randomization methods, allocation concealment, and blinding of outcome assessors.

Concerning harms, Chen et al. (2016) found no significant difference in all-cause discontinuation of TENS compared to control.(146) The uncommon, mild potential harms of TENS included increased pain, skin breakdown, redness, and skin irritation.(147,150) The benefits of TENS appear to be small, short-term effects, which are unlikely to be clinically significant. Within the SR by Chen et al. (2016), there was insufficient evidence to demonstrate clear effectiveness of a particular type of TENS application or stimulation frequency in comparison to interferential stimulation.(146) The systematic evidence review also did not yield any evidence examining the use of TENS for HOA.

The Work Group also considered patient preferences, feasibility, and subgroup considerations. Patients with comorbidities may not be able to participate in an exercise program. This intervention may benefit these patients if other non-surgical treatments are not feasible. The Patient Focus Group noted that patients view exercise programs, including physical therapy, as helpful, but pain can impede successful adherence to an exercise program. TENS may offer short-term pain relief. In patients who had prior success with using TENS therapy for pain relief, a provider could consider TENS as an adjunct therapy for short-term pain relief.

The systematic evidence review specifically searched for but was unable to find studies meeting the inclusion criteria for other types of electrotherapeutic devices (e.g., H-Wave, Alpha- Stim, Biowave). Considering the resource use and lack of clear effectiveness demonstrated for these devices, there is a lack of evidence to recommend these devices over TENS for use in clinical practice in knee or hip OA.

The Work Group systematically reviewed evidence related to this recommendation.(146-150) Therefore, it is categorized as a Reviewed, Not Changed recommendation. The Work Group’s confidence in the quality of evidence was Very low. There were significant limitations in the evidence given the heterogeneity of methods, application of devices, size of the studies, risk of bias, and inconsistent results on pain and function. The benefits of TENS for OA of the knee slightly outweighed the harms. Patient preferences and subgroup considerations also impacted this recommendation. Thus, the Work Group decided upon a Neither for nor against recommendation.

E. Pharmacotherapy

a. Topical Pharmacotherapy

Recommendation

10. For osteoarthritis of the knee, we suggest topical capsaicin.

(Weak for | Reviewed, Amended)

Discussion

Topically applied capsaicin has been used for the management of various types of pain, including neuropathic pain syndromes (e.g., postherpetic neuralgia, diabetic neuropathy, post-mastectomy pain) and pain arising from OA. Although topical capsaicin is generally used as adjunctive therapy, it may be used as monotherapy in patients with mild-to-moderate OA pain. Capsaicin reversibly depletes substance P (SP), an endogenous neuropeptide involved in the pathogenesis and modulation of pain. Capsaicin is derived from chili peppers, and its application stimulates the release of SP, initially causing a painful, burning sensation. With prolonged exposure and continued application, SP is depleted from afferent neurons, and transmission of painful stimuli is reduced or absent.

Adverse events include temporary burning, stinging, and pain at the application site. A SR by Laslett et al. (2014) included five RCTs comparing topical capsaicin 0.025-0.075% versus placebo and one trial comparing Civamide 0.075% (zucapsaicin, cis-isomer of capsaicin, is not available in the U.S.) to placebo.(151) All five RCTs assessing the benefit of topical capsaicin were relatively small (n=475) and of short duration (<3 months). Four were already a decade old when this data was used in the previous CPG evidence review. Among the studies included in Laslett et al. (2014),(151) Deal et al. (1991),(152) Altman et al. (1994),(153) and Kosuwon et al. (2010)(154) enrolled patients with OA of the knee. McCarthy et al. (1992)(155) enrolled patients with OA of the hand and McCleane (2000)(156) enrolled patients with OA in mixed joints (e.g., knee, shoulder, hand, hip). Evidence from the SR supports at least a moderate effect of capsaicin (SMD= 0.44) in reducing moderate pain associated with OA.(151) Studies included in the SR evaluated the benefit of capsaicin as monotherapy, with background acetaminophen or acetaminophen as an adjunctive treatment for improving pain associated with OA. AEs of capsaicin were local (i.e., burning, stinging, and pain at the application site) and reported in 35- 100% of patients randomized to capsaicin, which resolved or declined in most patients with continued use. No systematic AEs were reported with capsaicin.

The new data collected as part of the 2025 OA CPG update did not reveal any significant new findings that would affect the previous recommendation for treatment of KOA with topical capsaicin. Thus, the above recommendation is based on evidence from the previous review. Given that there was no evidence for or against use of topical capsaicin for HOA in the previous or most recent evidence review, it was decided to eliminate the previous recommendation addressing use of capsaicin for HOA. The Work Group determined that the benefits of use outweighed the harms, which was why the recommendation was maintained as a Weak for supporting the use of topical capsaicin for KOA.

Topical capsaicin provides an alternative means of pain control for patients that would prefer to avoid systemic therapy. Given that it does carry the risk of application site burning, and that the overall effect size from use is small, it was decided to maintain a Weak for recommendation supporting its use for KOA.

Patients and caregivers should be educated regarding the potential benefits of capsaicin treatment, the limited harms, the importance of adherence to therapy since an adequate trial may take up to 2-4 weeks; to wash their hands thoroughly after use; and to avoid contact with irritated skin, eyes, or mucous membranes. Although capsaicin does not possess systemic AEs and may be preferred in patients with multiple comorbidities who need to limit the use of oral therapies for

OA, some patients may be unable to tolerate the AEs. However, the local AEs resolve with continued use.

The Work Group systematically reviewed evidence related to this recommendation, primarily from the Laslett et al. (2014)(151) systematic review cited in the previous CPG. The previous recommendation was modified to reflect that its use is not necessarily limited to only pain relief. Therefore, it is categorized as Reviewed, Amended. The Work Group’s confidence in the quality of the evidence was Low. The body of evidence had some limitations including the date of collection in some cases over a decade ago, as there was no new evidence identified that meet inclusion criteria for this CPG update. The benefits of topical capsaicin outweighed the potential harms as Laslett et al. (2014)(151) supports a moderate benefit of topical capsaicin administered 3-4 times daily in reducing pain associated with OA. Patient values and preferences had some variation, with some preferring to use nonsystemic therapy options, and some having concerns for efficacy with topical treatment compared to systemic. There is also a common side effect noted with use of topical capsaicin of burning at the application site. Thus, the Work Group decided upon a Weak for recommendation for capsaicin use for KOA.

Recommendation

11. For osteoarthritis of the knee, we suggest topical non-steroidal anti-inflammatory drugs.

(Weak for | Reviewed, New-replaced)

Discussion

Topical NSAIDs are a common first-line measure of pharmacotherapy for mild KOA, with availability increasing to the public since it was approved for distribution without a prescription in the U.S. in 2020. Topical diclofenac is the most commonly available form of topical NSAID and has been shown to have between 5-to-17-fold lower systemic absorption when compared to oral NSAIDs. The most commonly noted adverse effect with use is dry skin at the application site; this favorable safety profile, is why it is frequently trialed by patients before systemic agents.(157)

The Work Group decided upon a Weak for recommendation for topical NSAIDs for patients with OA of the knee, which changed from the previous Strong for recommendation. This was based on new evidence comparing topical to oral pharmacotherapy, which came from one SR and one NMA. Zeng et al. (2021)(158) also showed that patients assigned to topical NSAIDs had improved function at 4 weeks, but no improvement in function at 12 weeks when compared to oral acetaminophen. Topical NSAIDs also had lower gastrointestinal (GI) adverse effects, no difference in cardiovascular (CV) adverse effects, and no difference in pain reduction in comparison to oral acetaminophen. Wolff et al. (2021)(159) showed that patients assigned to oral diclofenac had greater functional improvement when compared to topical diclofenac, but no difference in pain reduction. The study also showed that there was no difference in pain reduction when comparing topical ketoprofen to oral celecoxib.

This recommendation considered that many patients express interest in avoiding systemic agents for pain control due to concern for risk of potential adverse effects.

The Work Group systematically reviewed evidence related to this recommendation based on the Wolff et al. (2021) and Zeng et al. (2021) SR and NMA (158-159). These studies showed mixed evidence of comparable efficacy vs lower efficacy of topical NSAIDs when compared to oral

NSAIDs and oral acetaminophen when assessing pain reduction and functional improvement, but lower incidence of adverse GI effects.(158,159) The strength of the recommendation was changed from Strong for to Weak for in this updated guideline. Therefore, it is categorized as Reviewed, New-Replaced. The Work Group’s confidence in the quality of the evidence was Very low. This was because of serious limitations identified in the included studies, including high risk of bias, short duration of trials (typically only 4 to 12 weeks), and inadequately reported key design elements. This included randomization, allocation concealment, and blinding of participants and outcome assessors. The included NMA also incorporated large numbers of poor- quality trials, further reducing confidence in pooled estimates. The benefits of topical NSAIDs for KOA outweighed the potential harm of adverse skin reactions associated with use. Patient values and preferences were similar because many patients prefer to avoid systemic agents for pain reduction when possible. Thus, the Work Group decided upon a Weak for recommendation.

b. Oral Pharmacotherapy

Recommendation

12. For osteoarthritis of the hip and knee, we suggest oral non-steroidal anti-inflammatory drugs or acetaminophen. (Weak for | Reviewed, Amended)

Discussion

Oral therapies with NSAIDs and acetaminophen remain a backbone of therapy and a key oral medication option for OA. Effect sizes are generally small and need to be weighed against the known harms of these medications. We address three key areas in this narrative, comparative efficacy data, foundational data for NSAID use, and foundational data for acetaminophen use. Each will be discussed in detail here.(160-171)

This evidence was generated from the key question “What is the comparative safety and effectiveness of oral pharmacotherapy for the treatment of OA of the hip and knee?” and includes analysis of the comparative efficacy of these agents as well as the evidence from the previous version of this guideline addressing their overall efficacy vs. placebo. The overall strength of most comparisons was very low with low ratings due to limitations in the methodological quality of the included RCTs, indirectness of evidence derived from NMAs, and imprecision of the results. Overall, this comparative efficacy data is mixed and does not favor one agent over another. In addition to these concerns the Work Group acknowledges the potential for publication bias.(160- 171)

Comparative Efficacy

Comparative effectiveness evidence for various pharmacological interventions used for OA was primarily drawn from a NMA by Beaudart et al. (2020).(160) Across nearly all comparisons, the overall GRADE of evidence is very low due to serious limitations, indirect comparisons, and imprecision. Individual comparisons are discussed in detail below.

Various comparisons were made for NSAIDs vs. acetaminophen. Specifically, comparisons between celecoxib, diclofenac, and naproxen against acetaminophen (or paracetamol) generally showed no statistically significant difference for the critical outcomes of function and pain at the 6- week follow-up period. Celecoxib vs. acetaminophen: function (SMD= 0.21) and pain (SMD= -

0.08) did not differ between the groups. Diclofenac vs. acetaminophen: function (SMD= -0.11) and pain (SMD= 0.40) did not differ between the groups. Naproxen vs. acetaminophen/paracetamol: function (SMD= 0.19) and pain (SMD= -0.14) did not differ between the groups. However, the comparison involving piroxicam suggested that it may be less effective than acetaminophen for function. Piroxicam vs. acetaminophen: Acetaminophen had a greater improvement in function scores (SMD= 1.17; 95% CI: 2.05 to 0.29). Piroxicam was also noted to have poorer functional outcomes compared to placebo. Pain did not differ between the two groups.(160)

When considering direct NSAID comparisons, head-to-head comparisons among celecoxib, diclofenac, naproxen, and piroxicam generally showed no difference in pain outcomes, but highlighted several functional differences where piroxicam performed less well. Celecoxib, diclofenac, and naproxen: When compared against each other (diclofenac vs. celecoxib, naproxen vs. celecoxib, and naproxen vs. diclofenac), function and pain did not differ among these three agents at 6 weeks. Piroxicam vs. celecoxib: The celecoxib group had a greater improvement in function scores (SMD= 0.96), though pain did not differ. Piroxicam vs. diclofenac: diclofenac showed a greater improvement in both function scores (SMD= 1.28) and pain scores (SMD= -0.67) compared to piroxicam. This specific comparison of function was the only outcome rated as low quality evidence. Piroxicam vs. naproxen: naproxen had a greater improvement in function scores (SMD= 0.98), while pain did not differ between the two.(160)

Non-steroidal Anti-inflammatory Drugs

Oral NSAIDs are commonly prescribed for OA of the hip or knee and are generally well tolerated. The long- term use of NSAIDs is limited by adverse events (e.g., increased CV events, gastric and duodenal ulceration and perforation, bleeding, and renal impairment). The risks of these complications increase with age, drug-drug and drug-disease interactions, and duration and quantity of use.(161) These risks are especially concerning in the patient population typically affected by OA, who tend to be older, often struggle with other chronic comorbidities, and may be vulnerable to the effects of polypharmacy. Alternative therapies to reduce these risks are limited.

The suggestion to consider NSAIDs for managing pain associated with hip and knee OA is supported by three SRs with NMAs for effectiveness and two SRs with meta-analyses focusing on safety.(162-166) The SR by Osani et al. (2019) focused on NSAID safety and also examined the durability of symptom relief.(165) Additionally, the Puljak et al. (2017) SR compared the effectiveness and safety of celecoxib versus placebo and other NSAIDs.(167) The SR by da Costa et al. (2017)(n=58,451) included 76 trials studying the use of NSAIDs or acetaminophen and found that all active treatments improved pain associated with OA of the hip or knee versus placebo.(163) However, not all treatments met the predefined criteria for a minimally important difference (MID) to be considered clinically significant.(163) Of the interventions meeting the criteria for MID (i.e., rofecoxib 25-50 milligram [mg], etoricoxib 30-90 mg, and diclofenac 150 mg), only diclofenac is available in the U.S. Comparatively, maximum daily doses of naproxen and ibuprofen had an estimated 80% probability of meeting the MID for pain reduction.

The SR by Stewart et al. (2018) evaluated 29 studies of commonly prescribed analgesics (e.g., NSAIDs [n=9 studies], cyclooxygenase-2 [COX-2 inhibitors] [n=9 studies]).(162) The relative reduction in pain from baseline was 34.3% for oral nonselective NSAIDs and 36.9% for COX-2 inhibitors. Both nonselective NSAIDs and COX-2 inhibitors performed statistically better than acetaminophen, which reduced pain by 32.5% (p<0.001). A SR by Jung et al. (2018) (n=44 studies) evaluated the comparative effectiveness of oral analgesics for KOA.(164) For improving WOMAC pain, etoricoxib ranked the highest, followed by naproxen, acetaminophen, and celecoxib. In a subgroup analysis stratified by baseline severity of pain and radiologic severity of OA, etoricoxib, celecoxib, aceclofenac, and meloxicam or aceclofenac were the highest ranked therapies in the more severe pain group. In the group with mild-to-moderate pain, tramadol, celecoxib, diclofenac, and acetaminophen ranked highest. In Jung et al. (2018), ibuprofen was not included in any of the studies.(164) Rofecoxib, etoricoxib, and aceclofenac are not commercially available in the U.S.

In a SR by Puljak et al. (2017) studying celecoxib for the treatment of OA, celecoxib was slightly superior to placebo and various alternative NSAIDs in improving pain and function.(167) However, because of limited and missing data from several studies and industry sponsorship, the authors expressed strong reservations about their findings.(167) In a SR and meta-analysis by Osani et al. (2019), the durability of pain relief from NSAIDs (measured over 2-26 weeks) in patients with KOA was systematically examined from data collected in 72 clinical trials (n=26,424).(165) Osani et al. (2019) noted a moderate effect of NSAIDs in reducing pain (SMD= 0.43) and improving function in patients with KOA, peaking at two weeks with the magnitude of benefit lessening after approximately eight weeks of treatment.(165) In the same SR, the incidence of GI AEs was statistically higher in the NSAID versus placebo groups at four weeks (RR: 1.38, 95% CI: 1.21 to 1.57).(165) CV AEs were not different between NSAIDs and placebo. Most of the AEs were temporary and minor in severity.

A SR by Curtis et al. (2019) (n=40 trials) examined the safety of COX-2 inhibitors.(166) Overall, drug-related AEs were increased in the COX-2 group versus placebo (RR: 1.21, 95% CI: 1.09 to 1.46). Upper gastrointestinal (UGI) AEs, including dyspepsia, gastritis, and heartburn, were also statistically higher versus placebo (RR: 1.19, 95% CI: 1.03 to 1.38). The risk for hypertension, heart failure, and edema was statistically higher for COX-2 inhibitors versus placebo. However, the risk for hypertension was not statistically significant when rofecoxib was removed from the analysis. Further details on considerations for selecting oral NSAIDs as well as information on NSAIDs and the risks of adverse UGI events, CV events, and renal disease can be found in Appendix I.

Acetaminophen

Acetaminophen has both analgesic and antipyretic effects but lacks potent anti-inflammatory activity. Acetaminophen in usual doses (2-4 g [grams] per day) was previously recognized as the preferred initial choice for the management of OA in most patients. Its use may still be preferred by providers for patients with more mild disease or mild-to-moderate symptoms of OA and in patients at risk for NSAID-induced adverse events (e.g., patients with renal disease, cardiovascular disease [CVD] or at risk for CVD, a history of GI ulcers, those receiving oral anticoagulants or corticosteroids [CS], and the elderly [i.e., aged >65 years]) although recent recommendations from the U.S. Food and Drug Administration (FDA) and voluntary labeling changes suggest a maximum daily dose of 3 g which may impact the overall efficacy.

A NMA by da Costa et al. (2017) and a SR by Leopoldino et al. (2019) showed clinically insignificant differences for acetaminophen versus placebo in reducing pain and improving function in patients with OA of the hip and/or knee.(163,168) There was not a dose-dependent effect for acetaminophen in the SR by Leopoldino et al. (2019).(168) However, in the NMA by da

Costa et al. (2017), there was a statistical improvement in pain and function with maximal doses of acetaminophen (3,900-4,000 mg/day) that was not demonstrated with lower doses.(163) However, differences were not clinically significant regardless of the dose of acetaminophen.(163)

A second SR NMA in KOA only, Jung et al. (2018), noted statistically significant benefits of acetaminophen in reducing pain in patients with mild-moderate pain.(164) In Jung et al. (2018), the benefit of acetaminophen ranked higher than some NSAIDs in patients with mild-to-moderate pain associated with KOA.(164) Jung et al. (2018) did not identify any relevant studies in patients with more severe baseline KOA pain.(164) In another SR and NMA by Stewart et al. (2018), the relative reduction in OA pain from baseline was 32.5% for acetaminophen, similar to NSAIDs.(162) Stewart et al. (2018) found that other classes of medications for knee and hip OA reduced pain by a statistically greater degree than acetaminophen (NSAIDs=34.3%, p=0.035; opioids [mostly tramadol]=35.4%, p=0.001; COX-2 inhibitors=36.9%, p<0.001; topical NSAIDs [knee and hand only]=40.9%, p<0.001).(162) The relative benefit of acetaminophen for reducing pain associated with knee and hip OA was greater in Stewart et al. (2018) than da Costa et al. (2017).(162,163)

Although acetaminophen has long been considered a relatively safe analgesic when taken in usual doses (up to 4,000 mg daily), the risk for acute liver injury and liver failure is increased in patients taking doses >4,000 mg daily.(169,170) In the SR by Leopoldino et al. (2019), the incidence of AEs did not differ between acetaminophen and placebo (RR: 1.01, 95% CI: 0.92 to 1.11).(168) The incidence of SAEs and withdrawal because of AEs between acetaminophen and placebo were not statistically different but the number of events was relatively small and the confidence intervals were wide. Abnormalities in liver function tests (LFTs) were higher with acetaminophen versus placebo (RR: 3.79, 95% CI: 1.94 to 7.39); however, the clinical significance of LFT elevation associated with usual doses of acetaminophen is unclear.

While not included in this CPG’s systematic evidence review and, thus, not considered in determining the strength of recommendation, a SR of observational studies by Roberts et al. (2016) explored rates of mortality and CV, GI, and renal AEs in patients taking usual doses of acetaminophen.(171) A dose-dependent statistical increase in mortality (n=1 study), CV (n=4 studies), GI (n=1 study), and/or renal events (n=3 studies) was observed with acetaminophen use versus no use. Although this suggests a potential risk for AEs, uncontrolled observational studies may represent a channeling bias based on use in selected patients with comorbidities and avoidance of NSAIDs.

Because of the potential for unintentional overdose from taking acetaminophen from multiple sources (e.g. prescription and over the counter (OTC) single and combination products >4,000 mg/day), suggested maximum doses have been reduced to <4,000 mg daily (e.g. 3,000 mg, 3,250 mg, ≤3,900 mg). However, professional discretion can be used if doses up to 4,000 mg daily are deemed necessary for individual patients. Maximum doses of acetaminophen should be limited to the shortest possible duration.

Consideration was given to the benefits vs. harms with benefits slightly outweighing harms. The Work Group notes benefits of improvement in pain and function with evidence suggesting that diclofenac, naproxen, acetaminophen, and celecoxib did not differ in efficacy for pain reduction and function. The potential harms associated with oral pharmacotherapy, which include CV, GI, and renal with NSAIDS and hepatotoxicity with acetaminophen must be considered when utilizing these agents. Some variation was noted in patient preferences for the use of these agents and with consideration given to known potential harms and multiple daily dosage requirements. The Work Group notes other considerations of cost, acceptability, and subgroup considerations. The cost to the system of oral pharmacotherapy is generally low (most are generic and so low cost per unit, but large volume of use). Individual patient acceptance of any given oral therapy may be limited by side effects or preference, and subgroup consideration plays a large role in managing risk. The risk/benefit profile of various medications may differ depending on an individual patient’s comorbidities (for example, differing CV and GI risks with NSAIDs, pregnancy status, etc.). Finally, the Work Group notes that the efficacy studies for acetaminophen were originally conducted at moderate to high doses of acetaminophen, up to 4g/day. Recent guidance has lowered the maximum daily dose to 3g/day, and this may impact efficacy.

The Work Group systematically reviewed evidence related to this recommendation.(160- 171) Therefore, it is categorized as Reviewed, Amended. The Work Group’s confidence in the quality of the evidence was Very low. The body of evidence had some limitations including the methodological quality of the included RCTs, indirectness of evidence derived from the single included NMA Beaudart et al. (2020) (55 RCTs in 1 NMA; n=13,633)(160) and imprecision of the results. Overall, this comparative efficacy data is mixed and does not favor one agent over another. The benefits of oral therapies of NSAIDs and acetaminophen improved outcomes of pain and function, based largely on evidence supplied from the prior guideline recommendation and slightly outweighed the potential harm of AEs which requires careful consideration of risk to the patient based on baseline characteristics. Patient values and preferences varied somewhat with consideration given to known potential harms and multiple daily dosages. Thus, the Work Group decided upon a Weak for recommendation.

Recommendation

13. For osteoarthritis of the knee, we suggest duloxetine depending upon patient characteristics and preferences. (Weak for | Reviewed, New-replaced)

Discussion

The Work Group agreed on a Weak for recommendation for the use of duloxetine in select patients with OA of the knee. Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI) and FDA indicated for the treatment of major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain. The evidence for this recommendation is based on eight RCTs, seven of which were included in the previous evidence review for the 2020 VA/DOD CPG. All studies were ≤18 weeks in duration and evaluated KOA. Only one trial by Wang et al. (2017)(172) also evaluated HOA. Most studies allowed concomitant NSAID use.

A 12-week RCT (n=66) by Illeez et al. (2022) investigated the effects of duloxetine and pregabalin in patients with KOA.(173) Significant improvements were noted in pain, function, QoL, depression, anxiety, and sleep disturbance for both drugs when compared with pre-treatment values. There was no statistically significant difference between the duloxetine and pregabalin groups in Short Form-36 (SF-36) bodily pain scores (duloxetine mean [M]) (standard deviation [SD])= 63.75(29.41) vs. pregabalin M(SD)= 66.83(25.02); p=0.911), VAS daytime scores (duloxetine M(SD)= 2.7(2.1) vs. pregabalin M(SD)= 2.1(2.12); p=0.179), VAS nighttime scores (duloxetine M(SD)= 2.6(2.14) vs. pregabalin M(SD)= 1.9(2.02); p=0.152), or Pittsburgh Sleep Quality Index (PSQI) scores for sleep (duloxetine M(SD)= 6.27(5.09) vs. pregabalin M(SD)= 5.9(3.52); p=0.522). Pregabalin was associated with better WOMAC pain (duloxetine M(SD)= 7.2(5.61) vs. pregabalin M(SD)= 4.2(4.29); p=0.020) and WOMAC function scores (duloxetine M(SD)= 22.93(17.08) vs. pregabalin M(SD)=14.5(14.98); p=0.043) than duloxetine. Patients randomized to duloxetine had higher baseline BMIs which may partially explain some of the better outcomes noted with pregabalin. Fewer side effects were noted in the duloxetine-treated group than in the pregabalin-treated group.

Six RCTs evaluated in a SR by Chen et al. (2019) (n=2,059) demonstrated that duloxetine achieved significant reductions in pain outcomes, including 24-hour pain scores, weekly 24-hour average pain scores, and a ≥50% reduction in weekly mean pain scores when compared to placebo at 10-16 weeks follow-up.(174) The same SR found a statistically significant improvement in physical function for patients in the duloxetine treatment arm at 10-16 weeks when compared to placebo. Five of the RCTs suggested that duloxetine increases the incidence of mild treatment- emergent AEs (e.g., GI toxicity, sexual dysfunction, mild insomnia).(174)

The evidence review only included short-term studies (≤18 weeks) of duloxetine’s safety and efficacy in managing pain associated with OA; as such, one must consider the risk of discontinuation syndrome after long-term use.(174,175) Patients should be educated that the medication is to be taken daily (not as needed) and discontinued only after close consultation with their prescribing provider. Slow tapering will almost always be required. Duloxetine prescriptions should start at doses ≤30 mg daily and be increased to a goal of 60 mg daily. If a patient is taking another class of antidepressant medication (e.g., selective serotonin reuptake inhibitor [SSRI]) for a comorbid mood disorder, providers should consider transitioning to an equivalent dose of duloxetine using a cross-tapering strategy to avoid the risk of serotonin syndrome. As an initial consideration for providers, duloxetine therapy should not be initiated if a patient’s estimated glomerular filtration rate (eGFR) is determined to be <30 milliliters (ml)/minute (min)/1.73 m². Of note, no other literature was reviewed looking at the use of different SNRIs for the treatment of OA of the hip or the knee.

While not included in our CPG evidence review, Leite et al. (2025) conducted a SR and meta- analysis which included the eight aforementioned duloxetine studies and one additional study on hand OA. This review found duloxetine 60 mg/day to be superior to placebo in pain and function in adults over the age of 40.(176)

In practice, duloxetine will likely be used as an adjunctive or alternative treatment after a trial of nonpharmacologic therapies and NSAIDs. It may be considered for earlier use in select patients with comorbid conditions (e.g., depression, anxiety, fibromyalgia, neuropathic pain) and in patients with central sensitization of pain. It is worth noting that the prevalence of depression is two to three times higher in patients with OA.(173) A large variation in patient values and preferences is likely given this medication’s development for and primary use as an antidepressant, need for scheduled administration, side effect profile (e.g., sexual side effects) and withdrawal potential.

The Work Group systematically reviewed evidence related to this recommendation.(172-176) Therefore, it is categorized as a Reviewed, New-replaced recommendation. The Work Group’s confidence in the quality of evidence was Very low. The body of evidence had a few limitations, including that most RCTs were short-term. This intervention’s benefits, including improvement in pain and function, slightly outweighed the small potential for harm. A large variation in patient values and preferences is likely given this medication’s classification as an antidepressant and its side effect profile. Thus, the Work Group decided upon a Weak for recommendation.

Recommendation

14. For osteoarthritis of the hip and knee, we suggest against initiating opioids (including tramadol). For patients already on long-term opioid therapy, refer to the current VA/DOD CPG for the Use of Opioids in the Management of Chronic Pain. ** (Weak against | Reviewed, Not changed) Discussion

Over the past two decades, increasing recognition of opioid-related harms has led to a reassessment of opioid prescribing for chronic non-cancer pain. Contemporary guidelines have emphasized multimodal and non-opioid approaches to pain management to improve safety; this includes the 2020 OA CPG, which suggested that opioids (including tramadol) offer no clinically meaningful advantage for pain related to OA of the hip or knee. In a recent comparative effectiveness study, Thorlund et al. (2022) confirm that the analgesic effect of opioids was equivalent to NSAIDs for KOA, translating to a 0.3-mm difference on a 100-mm VAS, which was below the threshold of clinical importance.(177)

All active treatments in the NMA produced only small to moderate improvements vs controls, and differences between interventions were not clinically relevant. Additionally, confidence in these estimates was low due to study limitations and indirectness.

These findings align with prior SRs by da Costa et al. (2014), Fuggle et al. (2019), and Toupin et al. (2019) which compared various opioids to no treatment, placebo, or active control for the treatment of hip or knee OA.(178-180) These studies demonstrated that opioids reduce pain intensity more than placebo but with relatively small effect sizes.

Similarly, treatment with opioids (except for tapentadol) improved physical function more than placebo, but the improvements were relatively small (KOA [SMD: -0.22, 95% CI: -0.41 to -0.04], HOA [SMD: -0.33, 95% CI: -0.93 to 0.28], and knee and hip OA combined [SMD: -0.29, 95% CI: - 0.38 to -0.20]). Opioids also consistently produced higher rates of AEs, including withdrawal symptoms, across all trials that were studied.

In a SR and meta-analysis of seven RCTs by Fuggle et al. (2019), tramadol was also associated with a higher risk of AEs compared to placebo.(179) A RCT by Bianchi et al. (2003) compared tramadol to acetaminophen and showed no statistically significant differences in pain reduction or study withdrawal due to AEs at seven days.(181)

** See the VA/DOD Clinical Practice Guideline for the Use of Opioids in the Management of Chronic Pain. Available at: https://www.healthquality.va.gov/guidelines/pain/cot/

RCTs by Pavelka et al. (1998)(182) Beaulieu et al. (2008)(183) and DeLemos et al. (2011)(184) compared NSAIDs to tramadol at 4 and 12 weeks demonstrating that NSAIDs reduce pain and improve function over tramadol. Tramadol was also associated with more AEs and more study withdrawals than NSAIDs.

Given the lack of clinically meaningful benefits and well-recognized risks of opioid therapy (including misuse, overdose, dependence, endocrine dysfunction, sleep-disordered breathing, falls, and fractures), the Work Group did not change the 2020 OA CPG recommendation.

However, the Work Group acknowledged that severe knee and/or hip pain, that has not responded to non-pharmacologic and non-opioid therapies, represents a particularly challenging subgroup. In such cases, opioid therapy may be considered on a selected basis, using a patient- centered approach that prioritizes safety when anticipated benefits outweigh risks. If pursued, treatment with opioids should be restricted to refractory, severe pain after failure of first-line strategies and administered at the lowest effective dose for the shortest duration feasible. The Work Group further recommended reevaluation of on-going therapy focusing on benefits, risks, and continued need.

The Work Group systematically reviewed evidence related to this recommendation.(177-184) Therefore, it is categorized as a Reviewed, Not changed recommendation. Confidence in the evidence was Low due to limited active-comparator or head-to-head trials and the predominance of short-term studies. Although opioids demonstrated modest short-term improvements in pain and function compared with placebo, the durability of these effects is unknown, and the observed benefits are unlikely to be clinically significant. In contrast, substantial risks, including withdrawal, misuse, opioid use disorder, overdose, endocrine dysfunction, sleep-disordered breathing, and falls were documented. Given this unfavorable risk-benefit profile, the Work Group suggested against initiating opioids for hip or knee OA, while acknowledging that selected patients may warrant consideration. Thus, the Work Group decided upon a Weak against recommendation.

c. Intra-articular Injections

Recommendation

15. For patients with persistent pain due to osteoarthritis of the knee inadequately relieved by other interventions, we suggest an intra-articular corticosteroid injection. (Weak for | Reviewed, Amended) 16. For patients with persistent pain due to osteoarthritis of the hip inadequately relieved by other interventions, we suggest an image-guided intra-articular, corticosteroid injection. (Weak for | Reviewed, Amended) Discussion

Intra-articular corticosteroids injections (CSIs) are commonly used as a non-surgical intervention for OA, aimed at reducing synovial inflammation and providing symptomatic pain relief. Given their widespread availability, rapid onset of action, and frequent use in clinical practice, particularly for patients who are not candidates for or are awaiting more definitive interventions, the Work Group evaluated CSIs as a potential recommendation despite uncertainty regarding durability of benefit and long-term outcomes. A small RCT by Paskins et al. (2022) compared ultrasound-guided intra- articular injections of triamcinolone and lidocaine vs placebo (lidocaine alone) for HOA and found short-term improvement in function at 2 and 4 months, but with no sustained benefit at 6 months.(185) A SR by Mojica et al. (2022) which included 33 RCTs comparing CS and placebo for KOA, similarly demonstrated clinically meaningful short-term improvements in function that regressed towards baseline over time.(186) In contrast, a small RCT by Malone et al. (2024) compared extended-release CS for KOA and found no clinically important difference from placebo.(187) A SR by Pereira et al. (2025) included 10 RCTs comparing CS to placebo for either hip or knee OA, reported heterogenous and largely neutral findings, including significant pain effect favoring placebo over betamethasone at 12 weeks, but no significant difference between methylprednisolone and placebo.(188) Overall, these studies suggest that intra-articular CSIs provide modest short-term functional benefit in some patients, but most high- quality evidence demonstrates no sustained advantage over placebo.

When comparing differences in SAEs for CS compared to placebo. Paskins et al. (2022) compared triamcinolone and placebo for HOA and reported one possible treatment-related SAE in the CS group (death from subacute bacterial endocarditis), while two members of the CS group and two members of the control group had non-treatment-related SAEs.(185) Malone et al. (2024) compared extended-release CS and placebo for KOA and found no significant difference in SAEs between intervention and control.(187) A SR with NMA found no clear difference in SAEs between CS and placebo.(188)

Only one study, a RCT by Paskins et al. (2022), compared CS with placebo and incorporated a measure of pain interference, finding a significant improvement in the Stanford Presenteeism Scale for the intervention group compared to the control group at two months but not at six months.(185)

The CPG systematic evidence review did not identify any new SRs or RCTs examining important outcomes identified by the Work Group (sleep and radiographic change). Additionally, the CPG systematic evidence review did not identify any new SRs or RCTs examining if CS should be avoided in the 3 months preceding knee or hip joint replacement surgery. However, it is common practice to delay surgical intervention with recent CSIs to the hip or knee.

Despite general consistency in the evidence supporting CS for knee and hip pain associated with OA, patient preferences and clinician practices vary. The Patient Focus Group noted inconsistencies in clinician practice regarding the frequency and total number of CSIs (some received injections every 3 months, while others received one injection throughout their lifetimes). Additionally, the Work Group and Patient Focus Group noted that some clinicians heavily relied on CSIs when a patient did not qualify for more invasive treatments. The Work Group recognized other implications, including resource use, with considerable variability in products (short versus extended release) available on the market at varying costs, variable clinician skill levels, the general need for imaging availability for hip intra-articular injections, and the increased feasibility of CSIs.

The Work Group systematically reviewed evidence related to these recommendations.(185- 188) Therefore, it is categorized as Reviewed, Amended. The Work Group’s confidence in the quality of the evidence was Very low. The body of evidence had some limitations, including risk of bias (185,188), a single RCT with a low number of events (185,187), and a lack of analysis details.(186,187) The benefits of intra-articular CSI to the hip or knee for OA primarily improve short-term pain, are accessible to almost all clinicians, and easy to perform compared to other interventions and procedures, slightly outweigh the potential harms of generally low SAEs, lack of demonstrated disease-modifying effects (i.e., prevention of structural progression or reversal of cartilage damage), and no clear long-term or sustained improvement in pain or functioning. Patient values and preferences varied somewhat due to varying levels of understanding, different products on the market, and potential avoidance of injections/needles or a desire for less invasive interventions. Thus, the Work Group decided upon a Weak for recommendation.

Recommendation

17. For patients with persistent pain due to osteoarthritis of the knee inadequately relieved by other interventions, there is insufficient evidence to recommend for or against an intra-articular viscosupplementation injection. (Neither for nor against | Reviewed, New-replaced) 18. For osteoarthritis of the hip, we suggest against the use of an intra-articular viscosupplementation injection. (Weak against | Reviewed, Amended) Discussion

Viscosupplementation injections (VSIs) (which refers to all synthetic HA preparations) are intended to improve joint lubrication in the setting of OA.(186,188-191) The CPG systematic evidence review identified 5 new SRs or RCTs examining the intervention of HA in hip or knee OA.

For KOA, the evidence showed mixed, generally small benefits. Two SRs Migliorini et al. (2024) and Mojica et al. (2022) reported inconsistent functional outcomes with intra-articular HA. (186,189) Migliorini et al. (2024) found no significant improvement in WOMAC compared with placebo at either 2-4 or 5-8 weeks.(189) Mojica et al. (2022) observed temporary improvement in WOMAC scores when analyses were stratified by molecular weight, with effects peaking at 3 months and declining thereafter.(186) Pereira et al. (2025) which included 38 RCTs comparing HA alone or HA combination products with placebo for hip or knee OA, found statistically significant improvement in physical function with HA alone at 12 weeks; however, the magnitude of benefit did not reach the threshold for clinical importance.(188) No significant functional benefit was observed for HA combined with diclofenac or triamcinolone compared with placebo.(186)

For HOA, the evidence base was more limited. Kubo et al. (2022) a small RCT evaluating HA plus diclofenac for HOA reported greater functional improvement at 12 weeks with HA than with placebo.(190) However, the overall body of evidence remained limited, and clinically important short- and long-term benefit was not consistently demonstrated. The Work Group also recognized that VSI is FDA-approved for KOA, but not for HOA in the U.S.

Evidence regarding SAEs was limited and somewhat inconsistent. Miller et al. (2021) conducted a SR of RCTs comparing HA with placebo for KOA and found no difference in SAEs between HA and placebo across 27 RCTs included in the meta-analysis.(191) In contrast, Pereira et al. (2025) which included 6 RCTs of patients treated for hip or knee OA, found that HA was associated with higher odds of SAEs.(188) A small RCT by Kubo et al. (2022) reported one serious treatment- emergent AE in the intervention group, ischemic colitis, and none in the control group.(190)

Prior evidence from the 2020 VA/DOD OA CPG Work Group systematic evidence review found VSI may improve pain related to KOA but lacked benefit in HOA.(192-196) The current evidence review similarly found inconsistent, short-term, and generally non-clinically important benefits in KOA, with uncertain effects on pain, function, and QoL. The evidence for HOA remained sparse, and no consistent clinically important benefit was identified. The systematic evidence review found no studies comparing VSI with placebo using pain interference as an outcome.

There is some variation in patient values and preferences. Some patients may prefer VSI after inadequate response to other interventions, including other intra-articular therapies, while others may wish to avoid injections, procedure-related discomfort, or treatments with uncertain benefit. Patient understanding of VSI products, prior treatment experience, and willingness to pursue repeat or procedure-based interventions may also vary. Product availability, local practice patterns, clinician familiarity, and cost may influence feasibility and acceptability. Resource use may differ by site, particularly when image guidance is required or when specific HA products are not readily available.

The Work Group systematically reviewed evidence related to these recommendations.(186,188- 191) Therefore, it is categorized as Reviewed, New-replaced for KOA and Reviewed, Amended for HOA. The Work Group’s confidence in the quality of the evidence was Very low for KOA and Low for HOA. For KOA, the Work Group judged that the balance of benefits and harms was uncertain. Benefits were inconsistent, generally short-term, and often did not meet thresholds for clinical importance, while SAEs appeared uncommon but were imprecisely estimated. Given the very low certainty of evidence for KOA, variable patient preferences, cost, product availability, and resource use, the Work Group decided upon a Neither for nor against recommendation. For HOA, the Work Group judged that the burdens and potential harms of VSIs slightly outweighed the uncertain benefits. These burdens include post-injection pain or inflammation, infection risk, need for image guidance, possible radiation exposure during fluoroscopy, cost, and resource use. Given the limited evidence base, lack of consistent clinically important benefit, and lack of FDA approval for HOA in the U.S., the Work Group decided upon a Weak against recommendation.

Recommendation

19. For osteoarthritis of the knee, there is insufficient evidence to recommend the selection of either corticosteroid or viscosupplementation injections over the other. (Neither for nor against | Reviewed, New-added) Discussion

Given differences in proposed mechanisms, cost, duration of effect, and patient-specific factors (e.g., comorbidities, preferences, and prior response to therapy), the Work Group evaluated the comparative effectiveness of CSI versus VSI to inform clinical decision-making. Only one SR by Pereira et al. (2025) included a comparison of functional outcomes for CS and HA interventions in a NMA.(188) Pereira et al. (2025) explored intra-articular interventions for knee and hip OA based on large (>100 patients/group) randomized trials, including CS, and HA, and HA combinations.(188) With a focus on minimally clinically important between-group difference, Pereira et al. (2025) found that triamcinolone had the highest probabilities of reaching the MID for pain intensity at weeks 2 and 6 compared to placebo, while HA had no effect on pain but a higher risk of dropouts due to AEs.(188)The authors found that RCTs at high risk of bias frequently reported implausible treatment effects, leading them to exclude high-risk-of-bias trials from the analysis of safety and physical function outcomes. Relative effectiveness for physical function across time (2 to 52 weeks) for all possible pairs of interventions found no evidence of superiority of any active treatment over the others. There was no measure of important outcomes, including sleep, QoL, and pain interference. There was no measure of SAEs as an outcome comparing CS versus HA.

Despite general consistency in the evidence supporting the use of CSI and VSI in OA, there is a paucity of evidence on the effectiveness of comparators. The Work Group considered cost- effectiveness as a consideration in clinician decision-making between the two interventions, but it was outside the scope of the systematic evidence review. The Work Group also recognized and considered subgroup factors that may lead a clinician to choose one product over another, such as Active-Duty operational readiness, military logistics and product availability (e.g., authorized medical allowance list [AMAL]), and patient conditions such as diabetes, inflammatory arthritis, or immuno-compromising conditions.

Patient preferences and values vary in their focus on pain and functional goals, as well as in expectations and understanding of products compared to others. Intra-articular VSI typically requires specialty consultation, potentially increasing cost, compared to CSI. Additionally, there are likely differences in the equity and availability of therapeutics depending on locality, insurance, institutional pharmaceutical agreements, and general supply.

The Work Group systematically reviewed evidence related to this recommendation.(188) Therefore, it is categorized as Reviewed, New-added. The Work Group’s confidence in the quality of the evidence was Very low. The body of literature had some limitations in quality, risk of bias, and wide confidence intervals that include the possibility of no difference and a small to moderate between-group difference. The benefits of improvements in pain, function, pain interference, QoL, and sleep were balanced with the potential harms of no long-term benefit, increased costs, a low risk of SAEs, and possible post-operative complications or delays in surgical intervention. Patient values and preferences varied somewhat because some patients may prefer or have knowledge of one product over another, prefer avoidance of needles/injectables, and have prior experience, either positive or negative, with a specific therapeutic. Thus, the Work Group decided upon a Neither for nor against recommendation.

F. Orthobiologics

Recommendation

20. For patients with persistent pain due to knee osteoarthritis, there is insufficient evidence to recommend for or against platelet-rich plasma. (Neither for nor against | Reviewed, Amended)

Discussion

Platelet-rich plasma (PRP) is an autologous blood-derived product created by processing whole blood to concentrate platelets into a small volume of plasma at levels above baseline. Following injection and activation, these concentrated platelets release growth factors and signaling molecules that are believed to help modulate inflammation, support tissue healing, and potentially facilitate repair processes within damaged tissues. Given the limited number of effective non-surgical treatment options available for patients with knee and hip OA, therapies such as PRP have generated considerable interest among clinicians and patients seeking additional strategies to improve pain, function, and QoL.

The Work Group recognized that PRP has a biologically plausible mechanism of action; however, its primary focus was on patient-centered outcomes, including pain, function, QoL, and safety. In one SR of 42 RCTs comparing PRP with HA, Xu et al. (2025) reported improvements in function, QoL, and pain favoring PRP, although PRP did not consistently outperform HA by a statistically significant margin.(197) Similarly, Pelluri et al.(2025), in a SR of 21 RCTs, found that PRP may improve function compared with CSI and placebo, with subgroup analyses suggesting potential benefit for both leukocyte-rich (LR) and leukocyte-poor (LP) PRP and a possible signal favoring LR preparations.(198) The Work Group acknowledged that some reported improvements in pain and function approached or met minimum clinically important difference (MCID) thresholds.

However, confidence in these findings was limited by several important methodological and clinical concerns. The study populations were generally younger, had lower BMI, and had earlier-stage KOA than many patients treated in VA and DOD settings, limiting generalizability. In addition, blinding was likely incomplete in many trials because of visible or physical differences between PRP and comparator injections, creating the potential for performance bias, expectation effects, or inadvertent signaling. Review of the individual RCTs also suggested that studies at higher risk of bias tended to report larger treatment effects. This concern was supported by a NMA within the evidence base, which found that higher-risk PRP trials produced treatment effects approximately four times larger than the single lower-risk PRP trial.(188) Further, substantial heterogeneity in PRP preparation, dosing protocols, comparators, patient selection, and outcome assessment further reduced confidence in the pooled estimates. Taken together, these limitations suggest that the apparent benefits of PRP may be overstated, and the current evidence remains insufficient to support a recommendation for its use in knee or hip OA.

In addition, patient values and preferences varied, with some patients favoring minimally invasive procedures while others preferred more definitive surgical intervention. Nevertheless, most patients expressed interest in having additional treatment options available to improve pain and function. These considerations must also be viewed within the context of broader feasibility and implementation challenges across the VA and DOD healthcare systems. Important practical considerations include the lack of standardized PRP formulations and dosing protocols, the need for specialized equipment and staff training, and variable treatment availability across VA and DOD facilities. Compared with other non-surgical interventional procedures, PRP may also result in higher costs to both patients and the healthcare system, while utilization patterns and the economic impact of widespread adoption remain uncertain. In addition, adverse effects were reported more frequently with PRP compared with placebo;

although, these events were generally mild, self-limited, and consistent with the expected physiologic response to the intervention.

The Work Group systematically reviewed the evidence related to this recommendation. (188,197,198) Therefore, it is categorized Reviewed, Amended. The Work Group’s confidence in the quality of evidence was rated as Very low due to substantial heterogeneity across studies, including variability in methodology, outcome measures, dosing protocols, and PRP formulations.(198) Additional limitations included inconsistent stratification by OA severity and significant variability in reported clinical outcomes.(197) Although some studies suggested potential improvements in pain, function, and QoL, these potential benefits were weighed against the risks of post-injection pain, inflammation, and uncertainty regarding the durability and generalizability of treatment effects. Consideration was also given to the variability in patient preferences, as some individuals favor less invasive treatment options whereas others prefer more definitive interventions. Given the limitations of the available evidence and the balance of potential benefits and harms, the Work Group decided upon a Neither for nor against recommendation.

Recommendation

21. For osteoarthritis of the hip, there is insufficient evidence to recommend for or against platelet-rich plasma injections. (Neither for nor against | Reviewed, Amended) Discussion

The Work Group systematically reviewed the evidence for PRP use in HOA. A SR by Mirghaderi et al. (2025),(199) found no difference in function outcomes on Harris Hip Score (HHS) or WOMAC scores comparing PRP versus HA or comparing PRP+HA versus HA alone in patients with HOA across 6 total RCTs. Unlike HHS mid-term and long-term outcomes PRP vs HA was statistically significant (favoring PRP) in HHS short-term outcomes (SMD -0.35, 95% CI: 0.65 to -0.05). There was no difference in safety and SAEs between groups. One study reported higher post injection pain reaction in the PRP group that resolved within a few weeks. This SR was limited by serious imprecision and methodological weaknesses notably the wide confidence intervals indicating that the true effect size remains uncertain. There was no difference noted in WOMAC scores, statistically significant improvement in HHS short-term outcomes was noted.

NSAIDs are avoided around the time of PRP treatment because they inhibit platelet activation and suppress the inflammatory signaling necessary for platelet-derived growth factors to stimulate tissue repair. Other implications include resource use for cost and availability of PRP machines, supplies, US machines, PRP procurement trained staff and standard operating procedures (SOPs). Future research priorities will be to compare PRP to sham treatments, placebo and/or CSI.

The Work Group systematically reviewed evidence related to this recommendation.(199) Therefore, it is categorized as, Reviewed, Amended. The Work Group’s confidence in the quality of the evidence was Very low. The body of evidence had some limitations including Very low strength of evidence, small sample, heterogeneity of the interventions, short term follow-up, incomplete or inconsistent reporting, limited reporting of AEs.(199) The benefit of short-term improved function was balanced with the harm of short-term post injection pain. Patient values and preferences were similar because patients want more options for treatment of OA. Thus, the Work Group decided upon a Neither for nor against recommendation.

Recommendation

22. For osteoarthritis of the knee, there is insufficient evidence to recommend for or against the following intra-articular injections (listed alphabetically):

• Amniotic tissue allograft suspension (e.g. BioDRestore™) • Autologous conditioned serum • Dextrose prolotherapy • Micro fragmented adipose tissue • Plasma rich in growth factor • Polynucleotides • Stem cell injections (e.g., mesenchymal, adipose- derived, and bone marrow- derived) (Neither for nor against | Reviewed, New-replaced) Discussion

Orthobiologic interventions are increasingly utilized for musculoskeletal conditions and are commonly described using regenerative or stem cell-based terminology. However, most currently available orthobiologic preparations are believed to exert their proposed effects primarily through paracrine signaling, immunomodulation, and modulation of the local inflammatory environment rather than through direct tissue engraftment or durable structural regeneration.

Most orthobiologics preparations share these theoretical mechanisms, paracrine signaling (secretion of cytokines/growth factors rather than tissue engraftment), immunomodulation (shifting pro- vs anti-inflammatory balance), matrix/scaffold support (providing extracellular matrix fragments), controlled inflammatory stimulation (prolotherapy model), and limited true regeneration evidence (differentiation claims exceed current in-vivo data).

Additionally, substantial heterogeneity exists in product sourcing, processing methods, cellular composition, concentration of bioactive factors, and administration techniques. These factors limit mechanistic consistency and complicate interpretation and generalizability of findings across studies.

Autologous Conditioned Serum

Autologous conditioned serum (ACS) is derived from a patient’s own blood incubated with a stimulatory surface to increase anti-inflammatory cytokines, particularly interleukin-1 receptor antagonist (IL-1RA). Its primary effect is reduction of IL-1 mediate cartilage catabolism. ACS functions primarily through anti-inflammatory modulation rather than tissue regeneration.

Amniotic Tissue Allograft Suspension

Amniotic tissue allograft suspension is placenta membranes or fluid from donor tissue. The primary mechanism is that it contains extracellular matrix proteins, growth factors, and anti- inflammatory mediators, acts as a biologic scaffold and paracrine signaling source, theoretical immunomodulatory and antifibrotic effects, and most commercially processed products do not contain viable stem cells, with the key concept being scaffold + signaling, not true stem cell therapy in most preparations.

Allograft suspensions are sourced from donor cartilage, bone, or connective tissues micronized or suspended. The primary mechanism is that it provides matrix fragments and biochemical signals intended to stimulate host repair, no cellular engraftment expected, and works through host-mediated remodeling, not donor tissue integration, with the key concept being structural + signaling support, not cell replacement.

Evidence from one RCT by Gomoll et al. (2021)(200) with 200 patients suggests amniotic suspension allograft (ASA) improved function better than either HA or saline however the same study found no difference in safety and SAEs between ASA and either HA or saline for safety/SAEs. Additionally, evidence from one RCT in one NMA by Pereira et al. (2025) suggests that ASA improves function more than placebo.(188) Both of these RCTs were limited by very serious methodological limitations and serious imprecision.

In 1 RCT by Pill et al. (2025)(201) comparing an amniotic tissue allograft (BioDRestore™, a morcellized injectable amniotic tissue allograft) versus steroid KOOS symptom score, KOOS activities of daily living (ADL) score, Single Assessment Numeric Evaluation (SANE) score, and Lysholm score for function improved in the BioDRestore™ group. The study findings suggest that KOOS pain score improved, but no difference was found in the VAS score. This study findings suggest that KOOS QoL score improved in the BioDRestore™ group, but no difference was found in the Veterans RAND 12-Item Health Survey (VR-12) physical component score (PCS) or mental component score (MCS). Interpretation of the results is limited by very serious methodological limitations, serious imprecision, and a small sample size (n=81).

Dextrose Prolotherapy

Dextrose prolotherapy is a hypertonic dextrose injection. The primary mechanism is that it creates a localized osmotic irritation to mild inflammatory cascade, intended to trigger fibroblast proliferation and collagen deposition, primarily used for ligament/tendon laxity models, not cartilage regeneration, with the key concept being controlled inflammatory stimulus to induce connective tissue strengthening.

No difference between Dextrose prolotherapy and all other treatments for function was found in one SR by Khateri et al. (2024)(202) including 11 RCTs. Evidence from six studies in one SR by Arias-Vazquez et al. (2022)(203) found hypertonic dextrose prolotherapy improved function better than HA (Effect size [SMD]: -1.31 (-1.05 [95% CI: -2.03 to -0.08]) and P-value: 0.03). No difference was found between dextrose prolotherapy and HA in this SR. Both SRs have very serious limitations in study quality and risk-of-bias, and serious imprecision.

Micro-fragmented Adipose Tissue

Micro-fragmented adipose tissue (MFAT) is a patient’s lipoaspirate mechanically processed. The primary mechanism of MFAT is that it contains stromal vascular fraction (SVF) including mesenchymal stem/stromal cells (MSCs), pericytes, and cytokines, function largely through paracrine signaling rather than differentiation, anti-inflammatory and angiogenic modulations are primary theoretical effects. The key concept of MFAT is the cell-assisted anti-inflammatory signaling more than cartilage rebuilding.

Evidence from 75 patients in 1 RCT by Richter et al. (2025)(204) suggests that MFAT improved function more than CSI or saline. This RCT has very serious limitations in study quality and risk- of-bias, and serious imprecision.

Plasma Rich in Growth Factor

PRP/plasma rich in growth factors (PRGF) is sourced by centrifuged autologous blood. The primary mechanism is the concentrated platelet α-granules release platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-β), vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), promotes angiogenesis, chemotaxis, and matrix synthesis signaling, LR vs LP formulations alter inflammatory profile. The key concept being growth-factor mediated signaling, not stem cell therapy.

Evidence from 3 RCTs in 1 SR by Migliorini et al. (2025)(205) showed mixed results for PRGF vs. HA for function. This SR demonstrated serious imprecision.

Polynucleotides

Polynucleotides (PN)/polydeoxyribonucleotides (PDRN) are sourced by purified deoxyribonucleic acid (DNA) fragments, often derived from salmon. The primary mechanism involves adenosine receptor subtype 2A (A2A) activation, resulting in anti-inflammatory effects and promotion of fibroblast activity and angiogenesis. The therapy contains no cellular component and acts through biomechanical modulation. The key concept being receptor- mediated anti-inflammatory and tissue support signaling.

Among 60 patients in one RCT by Kim et al. (2023)(206) comparing intra-articular polynucleotide (IA PN) to high molecular weight hyaluronic acid (HMWHA), no difference was noted for function or safety. Evidence from another RCT by Stagni et al. (2021)(207) suggests Polynucleotides Highly Purified Technology (PN-HPT) and HA improved function better than HA alone. These RCTs have very serious limitations in study quality, risk-of-bias, and serious imprecision.

Stem Cell Injections

Allogeneic umbilical cord derived allografts are donor derived biological products containing extracellular matrix components and bioactive molecules that may modulate inflammation and support tissue repair through paracrine signaling.

Adipose-derived stem/stromal cell injections are sourced by enzymatically or mechanically isolated SVF. The primary mechanism is that immunomodulation via secretion of interleukin-10 (IL-10), TGF-β, VEGF, etc., potential chondrogenic differentiation is theorized but not consistently demonstrated in vivo, predominantly paracrine trophic support rather than direct tissue replacement, with the key concept being immune modulation plus trophic signaling to structural regeneration.

Bone marrow aspirate concentrate (BMAC) is sourced from iliac crest bone marrow aspirate, centrifuged. The primary mechanism of BMAC is that it contains MSCs, hematopoietic cells, platelets, and cytokines, functions through paracrine signaling and immune modulation, true stem cell differentiation into cartilage is theoretical and limited in clinical evidence. The key concept being mixed cellular plus growth factor milieu with signaling predominance.

In a SR comparing stem cells to placebo, evidence from 7 RCTs in one SR by Whittle et al. (2025)(208) suggests that stem cells improve function better than placebo at up to 6 months, but at later time points no between group difference was demonstrated. Four RCTs from this SR suggest that autologous stem cells improve function better than placebo, but there is no difference between allogenic stem cells versus placebo. Seven RCTs from Whittle et al. (2025) did not show any difference between stem cells or placebo for safety or SAEs.(208)

In one SR comparing stem cells to no treatment, usual care (analgesia, weight loss, exercise), a short-term benefit in function was noted, but this effect was not demonstrated at every point between 3 months to 1 year.(208) Evidence from one RCT in one SR by Whittle et al. (2025) was unable to find a difference between stem cells and no treatment/usual care for safety and SAEs.(208)

One RCT in one SR (208) comparing stem cells to glucocorticoids failed to show difference between stem cells and glucocorticoids. Evidence from this study was unable to find a difference between stems cells and glucocorticoids for safety or SAEs.

Evidence from 5-7 RCTs in one SR (208) suggest that stem cell injections are better than HA for improving function after three months. Functional outcomes were assessed at different follow-up time points. 5 RCTs reported function at >3 to 6 months follow-up, and 7 RCTs reported function at >6 months to 1 year follow-up. Five RCTs in this SR failed to show any difference between stem cells and HA for safety or SAEs. Evidence from one RCT in one SR suggests stem cells are better than oral acetaminophen for improving function. In one SR by Whittle et al. (2025)(208) one RCT did not show difference between stem cells and NSAIDs/HA/Physical Therapy/HA for safety or SAEs. This SR had very serious limitations in study quality, risk-of-bias and serious imprecision.

Evidence from 4 RCTs in one SR by Han et al. (2024)(209) was unable to find differences between BMAC and other treatments for improving function. Evidence from 8 RCTs in this SR comparing BMAC versus other treatments including HA was unable to find a difference between BMAC and any other treatment for safety/SAEs. This SR had serious limitations in study quality, and serious imprecision.

In one SR by Dhillon et al. (2025)(210) evidence from 9 RCTs comparing autologous adipose- derived mesenchymal stem/stromal cells (ADMSC) versus a variety of other treatments (analgesia, exercise and weight management) suggest that autologous ADMSCs were better than other treatments for improving function. Two RCTs from this SR found mixed results for allogenic ADMSCs for function.

In one SR (210) comparing autologous bone marrow derived (BMD)-MSC versus control, two RCTs found mixed results for function, and no difference for pain interference. One RCT from this SR found allogenic placental MSCs improved function up to 8 weeks (p<0.05) better than control, after which there were no differences between the groups.

Allogeneic umbilical cord derived allografts are donor derived biological products containing extracellular matrix components and bioactive molecules that may modulate inflammation and support tissue repair through paracrine signaling. Evidence from two RCTs in one SR by Dhillon et al. (2025)(210) found mixed results for allogeneic umbilical cord derived analysis versus control for function. 16 RCTs in this SR found no difference in safety/SAEs when comparing all types of stromal cells injections to control. Very serious imprecision was present, with wide confidence intervals in this study.

Six studies in one SR by Ishak-Samrin et al. (2025)(211) suggest Wharton’s jelly MSCs improve function better than placebo versus HA; no difference between Wharton’s jelly MSCs and HA was found for safety/SAEs. Very serious limitations and serious imprecision were present in this SR largely due to reliance on narrative reporting and insufficient quantitative data.

Riggle et al. (2024)(212) in one SR, including studies from 11 RCTs, was unable to find a difference between stem cell and non-stem cell treatments for safety. This SR has very serious limitations in study quality, risk-of-bias, and serious imprecision.

MSC improved function and pain more than comparator treatments in one SR by Xie et al. (2024).(213) The grade of evidence for these outcomes was moderate. This study has serious limitations in quality.

Mixed results were found in one NMA by Zhang et al. (2022)(214) including 10 studies comparing stem cells versus cell-free methods for safety/SAEs. This NMA has serious limitations in study quality, and serious imprecision.

Summary of Findings for Stem Cell Injections

Studies provided very low-quality evidence. Benefits and harms appear balanced with potential improvements in pain and function. AEs may include post injection pain, inflammation, or infection. Patient preferences vary with some expressing ethical concerns or reservations about experimental treatments. Some patients express interest in biologic or orthobiologic injections when conventional options offer limited relief. Others prioritize interventions with robust safety and efficacy evidence and may be less willing to pursue emerging therapies. Additional considerations include high cost, limited insurance coverage, treatment availability, and the need for guidance methods such as US or fluoroscopy for needle placement. Feasibility and resource considerations also influenced this recommendation. Orthobiologic products are not widely available in VA/DOD clinical settings, and access may require referral outside the health system, potentially introducing cost burden or inequity. Subgroup considerations for Veterans and Service Members include high rates of joint overuse, traumatic joint injury, and physically demanding occupational roles; however, the included studies did not address these specific populations, limiting applicability. Exploratory mechanistic studies were not included in the evidence review and therefore did not influence the strength of this recommendation.

The Work Group systematically reviewed evidence related to this recommendation.(188,200- 214) Therefore, it is categorized as Reviewed, New-replaced. The Work Group’s confidence in the quality of the evidence was Very low. The body of evidence had some limitations including small samples. The benefits of intra-articular orthobiologics were pain relief and improvement in function balanced with the potential harm of post-injection pain and inflammation which was small. Patient values and preferences varied somewhat because some patients may have ethical concerns with stem cell treatment and experimental treatments. Thus, the Work Group decided upon a Neither for nor against recommendation.

Recommendation

23. For osteoarthritis of the knee, we suggest against the following intra-articular injections (listed alphabetically):

• Atelocollagen • Autologous Protein Solution (or APS, e.g. nSTRIDE®) • Low molecular weight human serum albumin • Sprifermin (Weak against | Reviewed, New-replaced) Discussion

PRP differs from other orthobiologics therapies in that it is an autologous platelet concentrate that delivers growth-factor mediated signaling to modulate inflammation and tissue repair, rather than providing exogenous cells, structural tissue matrices, or inflammatory stimulants. A RCT by Nooh et al. (2023)(215) included in a SR of seven studies involving 2,939 patients found no difference in function or pain between low molecular weight fraction of 5% human serum albumin (LMWF-5A) or placebo at 12 months. No difference in safety was found between LMWF-5A or placebo. Evidence from a single RCT included in one NMA by Pereira et al. (2025) found no difference in function or safety between Sprifermin vs. placebo.(188) Similarly, one RCT from this NMA found no difference in function or safety between Atelocollagen vs. placebo for function or safety/SAEs. In one RCT by Ross et al. (2024),(216) there was no difference in pain, function, or QoL that were observed between nSTRIDE® or saline group and no side effects were recorded in this study.

Although no SAEs were reported in the included studies, the certainty of evidence regarding harms is limited. Given the low strength of evidence for benefit and limited reporting of AEs, the balance between benefits and harms remains uncertain. There was some variation in patient values and preferences. Some patients may have reservations regarding experimental treatment. Additional implications include the acceptability of the orthobiolgics given they are not FDA approved and are considered experimental, need for resources to support PRP delivery, including PRP processing equipment, site specific availability of US equipment, cost considerations, staff training for PRP procurement, and the development of clear standard operating procedures. Cost of these treatments, given lack of medical insurance coverage for these experimental treatments can be concern for many. High cost of orthobiologics, availability of these treatments, and US machine use should be considered. Equity of treatment may differ depending on patients’ geographical location.

The Work Group systematically reviewed evidence related to this recommendation.(188,215,216) Therefore, it is categorized as Reviewed, New- replaced. The Work Group’s confidence in the quality of the evidence was Very low. These RCTs consistently demonstrated no evidence of benefit for pain, function, QoL, or safety outcomes. The body of evidence had some limitations including lack of standardized protocols for orthobiologics, and outcome measurement heterogeneity. Patient values and preferences varied somewhat because some patients may have concerns with experimental treatments. Thus, the Work Group decided upon a Weak against recommendation.

G. Interventional Procedures

Recommendation

24. For the treatment of osteoarthritis of the knee, we suggest against geniculate artery embolization. (Weak against | Reviewed, New-added) Discussion

Geniculate artery embolization has been proposed as a non-surgical, procedural intervention for the treatment of osteoarthritis of the knee. Geniculate artery embolization is a minor, nonsurgical outpatient procedure that blocks the blood supply to the knee’s synovial via cauterization or injection of an embolic material (e.g. permanent microspheres or temporary agents such as imipienem and cilastatin). Reducing this blood flow is hypothesized to reduce local inflammation, neoinnervation, and neovascularization. The SR reviewed for the CPG included 14 studies utilizing a variety of techniques for geniculate artery embolization with variable outcomes.(217) The three RCTs in this SR failed to show a significant improvement in functional outcomes of geniculate artery embolization over sham procedures.(217) Considering pain, one of the RCTs reported a significant improvement at one month but not at longer intervals, and the other two RCTs did not show significant improvements in pain.(217) Notably, subgroup analysis showed a disproportionate response in patients with central sensitization, suggesting that geniculate artery embolization may have a role for pain conditions other than OA. This finding reinforces the recommendation in Appendix I to distinguish nociceptive from nociplastic pain prior to selecting interventional or procedural treatments. Patients whose pain is primarily centrally mediated are unlikely to derive sustained benefit from peripherally targeted procedures such as geniculate artery embolization.

No SAEs were reported in any of the 14 studies included in this SR.(217) However, providers should be aware of risks for geniculate artery embolization, which may include infection, post- procedural pain, and significant activity restrictions following the procedure.

Patients and providers are interested in additional non-surgical interventional procedures in the treatment of OA of the hip and knee. Compared to other non-surgical interventional procedures, geniculate artery embolization may incur higher costs to the healthcare system and patient, require more strict and longer activity restrictions, and may not be widely available.

The Work Group systematically reviewed evidence related to this recommendation.(217) Therefore, it is categorized as Reviewed, New-Added. The Work Group’s confidence in the quality of the evidence was Very low. The body of evidence had some limitations including lack of clarity in blinding procedures, high placebo response rates, varying outcome measures, overlapping interventions, variability in embolization technique, and inclusion of non- comparative studies.(217) The harms and burdens of geniculate artery embolization for OA of the knee slightly outweigh the potential benefits. Patient values and preferences were similar. Patients may be interested in additional non-surgical procedural interventions to treat OA but would want a clearly demonstrated benefit before agreeing to such procedures. Given that geniculate artery embolization may be more burdensome than other non-surgical procedures for the treatment of OA of the hip and knee, the harms outweigh the potential benefits. Thus, the Work Group decided upon a Weak against recommendation.

Recommendation

25. For the treatment of osteoarthritis of the knee, we suggest against geniculate nerve block. (Weak against | Reviewed, New-added) Discussion

Geniculate nerve blocks (GNB) have been studied both as a direct treatment for KOA and as a predictor of response to radiofrequency ablation (RFA) of the geniculate nerve. GNBs are minor, nonsurgical outpatient procedures where a local anesthetic is injected into the geniculate nerve. Blocking the innervation to the knee may reduce pain by disrupting pain signals from the knee. Here, we focus solely on GNB’s role in the treatment of KOA. The Work Group reviewed one SR that included eight studies by Almeida et al. 2025.(218) Six studies failed to show a clinically significant improvement in function or pain over comparators (i.e. standard of care, physical therapy, or alcoholic neurolysis).(218) One study showed short-term benefits in pain and function compared to placebo that was not sustained past 4 weeks.(218) Similarly, one study that compared GNB to intra-articular CS reported a temporary improvement in pain but no clinically significant difference in functional outcomes.(218) No SAEs were reported in the eight studies included in this SR.(218)

GNB for KOA appears to be a relatively safe procedure, however the evidence base is variable with the majority failing to show efficacy in multiple outcome measures including function, pain, fatigue, sleep, or QoL. The Work Group acknowledges that interventionalists may perform GNB when considering if RFA may benefit a patient. Commenting on that practice is beyond the scope of this CPG. The Work Group suggests against GNB as a treatment for KOA on its own.

The Work Group systematically reviewed evidence related to this recommendation.(218) Therefore, it is categorized as Reviewed, New-Added. The Work Group’s confidence in the quality of the evidence was Very low. The body of evidence had some limitations including heterogeneous patient populations, varying outcome measures, overlapping interventions, variable comparators, and inclusion of non-comparative studies.(218) The harms and burdens of GNB for KOA slightly outweighed the potential benefits. Patient values and preferences were similar because patients may be interested in additional non-surgical procedural interventions to treat OA but would want a clearly demonstrated benefit before agreeing to such procedures. Thus, the Work Group decided upon a Weak against recommendation.

Recommendation

26. For the treatment of osteoarthritis of the knee, there is insufficient evidence to recommend for or against the use of radiofrequency ablation. (Neither for nor against | Reviewed, New-added) Discussion

The Work Group reviewed two SRs of 39 studies by Almeida et al. 2025, Liu et al. 2024 (218,219) and one NMA of 12 RCTs by Park et al. 2024(220) that reported on RFA of the geniculate nerve for KOA. RFA is a minor, nonsurgical outpatient procedure that uses electrical stimulation to destroy sensory nerves. Ablating the geniculate nerve may reduce pain signals from the knee. RFA for KOA showed mixed results for improvement in function. The NMA by Park et al. (2024)(220) and one of the SRs (219) favored RFA over a variety of comparators including sham procedures, stem cells, HA, intra-articular CS, oral NSAID, PRP, and dextrose prolotherapy. However, the effect size was not clinically significant in this SR,(219) and the other SR failed to find a significant difference in function between the RFA and comparator groups.(218) Pain outcomes also showed mixed results. Liu et al. (2024) reported improvements in pain at 2, 4, 12, and 24 weeks follow up.(219) Almeida et al. (2025) reported a significant improvement in pain at 4-12 weeks, but not at 24-48 weeks.(218) Park et al.(2024) found no difference in pain or QoL outcomes.(220)

No SAEs were reported in one of the SRs.(218) SAEs were not discussed in the other SR (219) nor in the NMA.(220) However, providers should be aware of risks for RFA, which may include infection, procedural pain, and post-procedural pain. Notably, while RFA protocols are variable, this procedure is longer than others (e.g. interventional ablation [IA] or GNB) with protocols lasting as long as 15 minutes.(219)

Increasing options for non-surgical interventional procedures in the treatment of OA interests’ patients and providers alike. Compared to other non-surgical interventional procedures, RFA may incur higher costs to the healthcare system and patient, entail more procedure-related discomfort given the duration of the procedure, and may not be widely available.

The Work Group systematically reviewed evidence related to this recommendation.(218-220) Therefore, it is categorized as Reviewed, New-Added. The Work Group’s confidence in the quality of the evidence was Very low. The body of evidence had some limitations including multiple comparators, a lack of clarity around blinding procedures, randomization or allocation concealment, and the measurement of the outcomes. Analysis of the results also suffered from the overlapping of the interventions,(218-220) serious indirectness and sparse connections in the NMA,(220) using the global WOMAC score to assess function,(219) and heterogeneity in RFA protocols.(218-220) The benefits and harms/burden of RFA for OA are balanced. While there’s mixed evidence of its efficacy, safety appears to be comparable to other recommended non-surgical interventions (e.g. intra-articular injections). Patient values and preferences were similar because patients may be interested in additional non-surgical procedural interventions to treat OA but would want a clearly demonstrated benefit before agreeing to such procedures. Thus, the Work Group decided upon a Neither for nor against recommendation.

Recommendation

27. For the treatment of osteoarthritis of the hip and knee, there is insufficient evidence to recommend for or against extracorporeal shockwave therapy. (Neither for nor against | Reviewed, New-added) Discussion

The Work Group reviewed a SR by Silva et al. (2023)(221) of 12 studies evaluating extracorporeal shockwave therapy (ESWT) for OA of the hip and knee. ESWT is a minor, nonsurgical outpatient procedure that applies pressure waves and shock waves locally, which are hypothesized to reduce pain by stimulating tissue repair, promote healing mechanisms, and reduce inflammation. The evidence suggested that ESWT may improve function and pain scores compared to sham or standard of care, particularly in the short term (3-10 weeks). However, the strength of evidence was rated very low due to methodological limitations across studies, including unclear blinding, randomization, and outcome measurement procedures. Additionally, high heterogeneity in pooled analyses and overlapping interventions reduced confidence in the findings. While individual studies in the >10-week meta-analysis showed statistically significant effects favoring ESWT, inconsistency across studies limited the reliability of these results and, collectively, the confidence intervals were wide and not statistically significant. Safety outcomes were not reported, and post- procedure restrictions on NSAID use may affect recovery.

Patient values and preferences were considered. ESWT may offer temporary improvements in pain and function, which some patients may find appealing. However, the lack of safety data and the requirement to avoid NSAIDs for six weeks post-procedure may cause hesitation in patients. Feasibility is limited by patient access and the need for specialized training for treatment providers. Acceptability may vary due to differences in technique and frequency, and the unpredictable benefit may reduce patient confidence. Resource use is also a concern, as ESWT requires costly equipment and setup, which may not be available in all clinical settings, particularly within VA/DOD systems.

The Work Group systematically reviewed evidence related to this new recommendation.(221) Therefore, it is categorized as Reviewed, New-added. The Work Group’s confidence in the quality of the evidence was Very low, due to multiple limitations in study design and reporting. These included unclear blinding and randomization procedures, lack of allocation concealment, and inconsistent outcome measurement. Additionally, the meta-analyses showed high heterogeneity, and many studies included overlapping interventions or non-comparative designs, further reducing confidence in the findings. While the evidence suggested that ESWT may improve pain and function scores in the short term (3-10 weeks), the durability of these effects remains uncertain. Safety data were not reported, and the requirement to avoid NSAIDs for six weeks post-procedure may interfere with recovery or patient comfort. The benefits of ESWT were therefore considered balanced with potential harms and burdens. Patient values and preferences were similar, with some patients potentially interested in non-invasive options, but others may be deterred by the lack of clarity around expected outcomes and procedural variability. Feasibility and resource use were also concerns, as ESWT requires specialized equipment, training, and may not be widely available in all clinical settings. Thus, the Work Group decided upon a Neither for nor against recommendation.

Recommendation

28. For the treatment of osteoarthritis of the hip and knee, there is insufficient evidence to recommend for or against radiation therapy. (Neither for nor against | Reviewed, New-added) Discussion

The Work Group reviewed one RCT evaluating low-dose radiation therapy for KOA by van den Ende et al. (2020).(222) Low-dose radiation therapy administers low-doses of radiation, typically 2 gray (Gy) or less, locally to the affected joint. Its mechanism of action in reducing pain is not fully elucidated, but it has been proposed to reduce inflammation in the targeted joint.(223) The study included 55 participants and compared radiation therapy to a sham intervention over 12 months. Across critical outcomes of function, pain, and SAEs, no statistically significant differences were observed between groups. The study reported no SAEs in the radiation group and three SAEs in the sham group, though none were deemed related to the intervention. The small sample size and lack of study for HOA contributed to a low strength of evidence. Given the limited data and absence of demonstrated benefit, the Work Group concluded that the evidence is insufficient to recommend for or against the use of radiation therapy for OA of the hip and knee.

Patient values and preferences were considered in the recommendation. While some patients may be open to non-invasive interventions, others may be deterred by the term “radiation” due to its negative connotation. The time burden associated with six treatments over two weeks, without demonstrated benefit, was also noted as a potential barrier. Resource use is significant, requiring specialized equipment and personnel, which may limit accessibility and equity, particularly in underserved or rural populations. Acceptability is further challenged by unclear benefits and patient apprehension. These factors collectively support the decision to refrain from recommending radiation therapy currently.

The Work Group systematically reviewed evidence related to this new recommendation.(222) Therefore, it is categorized as Reviewed, New-added. The Work Group’s confidence in the quality of the evidence was Low, primarily due to the limited number of studies, small sample size, and lack of data for HOA. The only available study, a single RCT, did not demonstrate significant differences in pain, function, or SAEs between low-dose radiation therapy and sham treatment. The benefits of radiation therapy were balanced with potential harms, which were minimal but included concerns about radiation exposure and treatment burden. Although no AEs were attributed to the intervention, the lack of efficacy and the need for multiple treatments over a short period raised concerns about resource use and feasibility. Patient values and preferences were similar, with some patients potentially interested in non-invasive options, while others may be deterred by the term “radiation”. Given the absence of demonstrated benefit, the logistical burden, and the potential for patient apprehension, the Work Group concluded that the evidence is insufficient to recommend for or against the use of low-dose radiation therapy for OA of the hip and knee. Thus, the Work Group decided upon a Neither for nor against recommendation.

H. Dietary Supplements and Nutraceuticals

Recommendation

29. For the treatment of osteoarthritis of the hip and knee, we suggest against the use of cannabidiol (CBD oil). (Weak against | Reviewed, New-added) Discussion

Having access to nutraceuticals, specifically including CBD, which was mentioned by the Patient Focus Group, is important to both Veterans and Active-Duty Service Members with painful OA. The Work Group reviewed the evidence to determine whether there are any benefits or harms associated with CBD for OA. There was a single RCT by Pramhas et al. (2023) that evaluated CBD versus placebo for the outcomes of pain, function and AEs.(224) No difference was found in any pain or functional measure. Regarding AEs, there was a notably higher incidence of elevations in gamma-glutamyl transferase (GGTA) in the group of patients taking CBD. The Work Group also considered other domains of the GRADE process and had concerns that this intervention had potential harm related to being a prohibited substance for Active-Duty Service Members. Given CBD formulations are unregulated, there was also Work Group concern for Veterans and federal workers that any CBD product may contain the active tetrahydrocannabinol (THC) component in cannabis and result in an abnormal urine toxicology. This could result in significant adverse outcomes including termination from federal service or tapering of long-term opioid therapy.

The Work Group systematically reviewed evidence related to this recommendation.(224) Therefore, it is categorized as a Reviewed, New-added recommendation. The Work Group’s confidence in the quality of evidence was Very low. The body of the evidence had some limitations including being limited to a single small study. The harms of CBD for OA of the hip or knee outweighed the benefits as evidenced by harms that were present (e.g., GGTA elevations and employment risks), and benefits of interest (e.g. pain and function) were absent. Patient values and preferences varied largely because of out-of-pocket costs, variability in formulations, uncertainty of purity of formulations, and potential adverse employment consequences. Finally, for all nutraceuticals, a more rigorous approach to product development and purity standards, dose ranging studies, and replication of RCTs by non-vested parties would be helpful in making more certain recommendations about the role nutraceuticals, including CBD, can or cannot play in the management of OA. Thus, the Work Group decided upon a Weak against recommendation.

Recommendation

30. For osteoarthritis of the hip and knee, there is insufficient evidence to recommend for or against the use of the following dietary supplements or nutraceuticals:

• Avocado and soybean extract • Boswellia serrata • Chondroitin • Collagen • Curcumin (active component of turmeric) • Ginger • Glucosamine • Glucosamine plus chondroitin • Methylsulfonylmethane (MSM)
• Omega-3 fatty acid • Pycnogenol (pine bark) • Rosehip • Specialized pro-resolving lipid mediators (SPMs) • Traditional Chinese medicine • Traditional Korean medicine Gyejigachulbutang (GCB) • Vitamin D • Vitamin E • Willow bark extract (Neither for nor against | Reviewed, New-replaced) Discussion

This recommendation examined 18 dietary supplements: avocado and soybean extract, Boswellia serrata (BS), chondroitin, collagen, curcumin, ginger, glucosamine, glucosamine plus chondroitin, MSM, Omega-3 fatty acids, pycnogenol (pine bark), rosehip, SPMs, traditional Chinese medicine, traditional Korean medicine GCB, vitamin D, vitamin E, and willow bark extract.(224-251)

The acceptability of and familiarity with dietary supplements likely vary across patients and providers. These supplements are widely marketed and available OTC. Furthermore, most dietary supplements included in this CPG’s systematic evidence review are not on TRICARE formulary or a part of the VA Pharmacy Benefit and, thus, would be an out-of-pocket expense for patients.

Also, the products used in the trials (e.g. laboratory standardized) may differ from what is found on a formulary, store shelves, or online (i.e., the consumer version). Dietary supplements are not as strictly regulated as pharmaceuticals and do not require FDA approval to be marketed to consumers. Furthermore, the FDA does not review supplements for safety and effectiveness before they are marketed.

It is also important to note that several of these dietary supplements have the potential for drug- supplement interactions. Providers should ask about and be aware of the dietary supplements their patients may be taking so that potential drug-supplement interactions can be mitigated, and when appropriate report AEs as indicated. Providers can assess drug-supplement interactions at the Natural Medicines Comprehensive Database.

Of the 11 interventions reviewed in the 2025 evidence base, no intervention showed any clinically meaningful difference in any critical or important outcome. Curcumin, vitamin D, avocado and soybean extract, ginger, and Omega-3 did show statistically significant improvement in function and/or pain.(225-228,231-233,236,241-243,245) However, the quality of the evidence was deemed very low due to insufficient blinding, or the effect size was so small the Work Group determined that any MCID was unlikely to be present.

As such, the Work Group did not assign a directional recommendation.(225- 228,231,233,236,241) For chondroitin, glucosamine, glucosamine plus chondroitin, and MSM, the evidence was mixed including one SR which found placebo to be better than combination intervention. However, in all cases evaluating chondroitin, glucosamine, or glucosamine plus chondroitin, the confidence in the evidence was very low and effect sizes or MCID was deemed by the Work Group to be likely below a clinically meaningful difference.(234,237,238,240)

The interventions of GCB and SPMs showed no difference from placebo in any numeric or clinically meaningful manner in any outcome assessed except possibly increased AEs (mild and reversable) with GCB.(229,232)

Seven interventions (collagen, pycnogenol, BS, willow bark, rosehip, vitamin E, and traditional Chinese medicine) were carried forward from the 2020 CPG with no new evidence identified during the 2025 update.(243-250)

CBD was removed from this group of nutraceuticals based on concerns about harms and is reviewed separately in Recommendation #29.(224)

The Work Group systematically reviewed evidence related to this recommendation.(224-251) Therefore, it is categorized as a Reviewed, New-replaced recommendation. The Work Group’s confidence in the quality of evidence was Very low. The body of evidence had significant limitations including small study sizes, risk of bias (e.g. uncertain blinding) and heterogeneity of dosing and follow-up times. Of note, some studies were industry funded. Given the low potential for AEs with most supplements, a possible signal of benefit with some nutraceuticals, and a patient voiced preference for non-medical alternatives, the Work Group determined the benefits slightly outweighed the harms. The risk of AEs or outcomes from potential drug-supplement interactions needs to be considered in individual patients. Thus, the Work Group decided upon a Neither for nor against recommendation.

I. Complementary and Integrative Health

Recommendation

31. For osteoarthritis of the knee, we suggest yoga or tai chi.

(Weak for | Reviewed, New-replaced) Discussion

Yoga and tai chi are distinct yet related mind-body practices that incorporate physical postures (yoga), slow and intentional movements (tai chi), breathing techniques, and mental focus to promote physical and psychological well-being. The evidence indicates that yoga and tai chi are generally safe interventions and may provide small but clinically meaningful short-term improvements in pain and function for patients with KOA. There is insufficient evidence to support a recommendation for or against yoga or tai chi for osteoarthritis of the hip.

Yoga

A SR by Lauche et al. (2019)(252) of nine RCTs found that for individuals with KOA, yoga improved physical function (SMD 0.64) and reduced pain intensity (SMD -0.75) compared to non-exercise controls. More recently, a RCT by Bennell et al. (2022)(253) evaluating a 12-week unsupervised online yoga program found a statistically significant improvement in function at 12 weeks compared to an educational control; however, this effect was not sustained at the 24- week follow-up after completion of the intervention, during which adherence declined. The Bennell et al. (2022) study reported no difference in pain between the groups.(253)

Regarding safety, the Lauche et al. (2019) review noted limited reporting of AEs.(252) The Bennell et al. (2022) trial reported no SAEs, although participants in the yoga group reported more non-SAEs (primarily musculoskeletal pain) than those in the education only control group (13% vs. 1%).(253)

Tai chi

A RCT by Chen et al. (2021)(254) found that for individuals with KOA, a 12-week tai chi program resulted in significant improvements in multiple measures of functional fitness (including the 2-minute step test, chair sit-and-reach test, and single-leg stance test) when compared to an educational control group. A SR by Hall et al. (2017), which was considered in the 2020 OA CPG, found statistically significant reductions in short- term disability (SMD -0.66) and pain (SMD -0.66) versus no treatment or usual care.(255)

Regarding safety, the Hall et al. (2017)(255) review did not specifically address SAEs, noting only that few AEs were reported in earlier reviews on the topic. Similarly, Chen et al. (2021) did not address AEs.(254)

The Work Group also considered patient values and preferences, feasibility, and subgroup considerations. Findings from the VA/DOD Patient Focus Group indicate that many Veterans and Service Members value managing the symptoms of OA through lifestyle and non- pharmacologic interventions. Participants reported familiarity with a range of complementary and integrative health (CIH) interventions and have experienced symptom relief though the benefits were often described as temporary or variable. Participants also expressed concerns about potential out-of-pocket costs.

From a feasibility standpoint, the Work Group noted that VA already supports yoga, tai chi, and related CIH modalities, and that many VA facilities and military treatment facilities offer these or similar programs at no cost to beneficiaries. However, availability and regular access may vary, including the availability of clinicians or instructors trained in specific CIH modalities.

Subgroup considerations include that yoga and tai chi obtained in community settings are generally not covered by TRICARE, which may limit access for some DOD beneficiaries. Although some individuals may be able to use healthcare flexible spending accounts to offset costs, this option is not universally available. However, many communities offer free or low-cost yoga or tai chi classes, and virtual options may also improve access.

The Work Group systematically reviewed new and previously reviewed evidence related to this new recommendation.(252-255) Therefore, this recommendation is categorized as Reviewed, New-replaced. The Work Group’s confidence in the quality of the evidence was Low for yoga and Very low for tai chi. The body of evidence was limited by a small number of studies, small sample sizes, and a lack of data on long-term effectiveness. The benefits of yoga and tai chi in improving function, pain interference, and pain were judged to outweigh the potential harms, which consisted primarily of small increases in non-serious AEs. Patient values and preferences varied somewhat, with many expressing interest in alternative treatment modalities while also expressing concern about out-of-pocket costs and long-term effectiveness. Thus, the Work Group decided upon a Weak for recommendation.

Recommendation

32. For the treatment of osteoarthritis of the hip and knee, there is insufficient evidence to recommend for or against:

• Acupressure • Acupuncture • Balneotherapy • Dry needling • Massage • Meditation • Mindfulness • Moxibustion • Mud therapy • Neurofeedback (Neither for nor against | Reviewed, New-replaced) Discussion

Integrative health brings conventional and complementary approaches together in a coordinated way. Integrative health also emphasizes multimodal interventions, which are two or more interventions such as conventional health care approaches (like medication, physical rehabilitation, psychotherapy), and complementary health approaches (like acupuncture, yoga, and probiotics) in various combinations, with an emphasis on treating the whole person rather than, for example, one organ system. Integrative health aims for well-coordinated care among different providers and institutions by bringing conventional and complementary approaches together to care for the whole person. Patient interest in these approaches (previously termed complementary and alternative medicine) is high. The use of complementary health approaches by American adults has surged, especially for pain treatment in the past several years.(256) Due to the popularity of these approaches we focused an entire key question on their safety and efficacy.

This section includes our review of and recommendation for 10 CIH interventions. The modalities reviewed included: acupressure, acupuncture, balneotherapy, dry needling, massage, meditation, mindfulness, moxibustion, mud therapy, and neurofeedback. While some promising evidence emerged, there was insufficient evidence to recommend for or against the use of any of these CIH interventions for the treatment of OA of the hip or knee.

Acupressure

Acupressure is a treatment in which a practitioner applies, or a patient can self-administer physical pressure to specific points on the body to relieve symptoms.(257,258) The practice is based on traditional Chinese medicine meridian theory and uses the same acupoints as acupuncture but using fingers, hands, or elbows instead of acupuncture needles. The putative mechanisms for acupressure include stimulation of self-healing, relief of muscular tension, endorphin release, suppression of peripheral inflammation, and modulation of pain signals.(258)

The evidence reviewed for acupressure in KOA included two RCTs, a pilot study by Cheung et al. (2020)(259) and a fully powered trial by Yeung et al. (2024)(258) from the same research group. Yeung et al. (2024)(258) compared self-administered acupressure (n=174) vs an education control arm (n=175). There were no differences between self-administered acupressure and control for function and pain interference. Participants in the acupressure group showed improved pain and QoL at the end of treatment compared to control participants in the larger trial but not in the pilot trial. Because no SAEs were reported in either study, acupressure is generally considered safe.

Acupuncture

Balneotherapy

Balneotherapy is a therapeutic practice that involves bathing in mineral-rich baths or pools and water immersion for health purposes and has been recognized by the World Health Organization as a complementary therapeutic approach.(264) Balneotherapy has been used for hundreds of years to treat musculoskeletal conditions such as OA, dermatological diseases, and chronic respiratory disorders. Its therapeutic benefits are believed to stem from anti-inflammatory, analgesic, antioxidant, cartilage protection, and immunomodulatory effects.(265)

Two relatively small RCTs by Adigüzel et al. (2022) and Cantista et al. (2020)(266,267) were reviewed. Adigüzel and colleagues (266) compared balneotherapy (n=28) versus hydrotherapy (n=25) with sham peloid therapy (mud therapy) in participants with KOA. In a slightly larger trial, Cantista et al. (2020)(267) compared balneotherapy (n=60) versus usual care (n=60) for KOA. Overall, results showed improved function, pain severity, and pain interference compared to usual care. However, outcomes (function, pain severity, and pain interference) were not statistically different between balneotherapy and hydrotherapy with sham peloid therapy. There was no difference between balneotherapy and usual care for QoL. Balneotherapy is considered safe with minimal side effects.(268)

Dry Needling

Dry needling is defined by the American Physical Therapy Association as an intervention using a thin filiform needle to penetrate the skin and stimulate underlying myofascial trigger points, muscular, and connective tissues for the management of pain and movement impairment. Dry needling results in both peripheral and central effects. Peripheral effects include decreased spontaneous electrical activity and acetylcholine at myofascial trigger, increase in vasoactive substances. Central effects include activation of supraspinal mechanisms namely diffuse noxious inhibitory control.(269)

We reviewed a SR by Jiménez-Del-Barrio et al. (2022)(270) that included seven RCTs of participants with knee or HOA. Five of the seven trials compared dry needling versus sham (n=191), and two trials compared dry needling to exercise (n=100). Note, all trials were small (less 50 participants), assessed only short-term effects (1 to 3-weeks), and evaluated dry needing in isolation rather than combined with other commonly used treatment modalities used in physical medicine/physical therapy settings. In KOA, there may be short-term benefits for pain severity.(271) For HOA, dry needling outperformed sham needling or exercise in three trials for short-term improvements in pain severity.

Only one of the seven RCTs (n=62) included AEs, reporting no SAEs in either the dry needling or exercise arms. Potential adverse effects include bruising, hematoma, infection, or nerve injury.

Massage

In a 2011 study, 82% of Veterans reported use of at least one CIH treatment and nearly all were willing to try such approaches for their pain.(272) Of all CIH approaches, massage was the most preferred by Veterans.(272) Massage is theorized to work through a variety of mechanisms to relieve pain.(273-275) These mechanisms include: 1) increased local blood circulation; 2) improved muscle tone; 3) increased joint flexibility; 4) heightened relaxation response; and 5) changed neuroendocrine and inflammatory status implicated in pain generation and sensitivity.

The evidence reviewed for massage for KOA included two small RCTs by Döner et al. (2024) and Sansila et al. (2019).(276,277) Döner et al. conducted a 3-arm trial that tested aromatherapy massage combined with physiotherapy (n=20) versus massage with sham aromatherapy (n=20) versus physiotherapy alone (n=20). In this trial, aromatherapy massage with physiotherapy improved function and pain severity compared to massage with sham aromatherapy or physiotherapy alone. There were no differences between study interventions for sleep. A comparative effectiveness trial (277) compared traditional Thai massage (n=30) versus diclofenac (n=30) in patients with KOA. While function improved in the massage arm compared to diclofenac at 6 and 12 weeks, there were no differences seen in pain severity and pain inference.

In the 2020 OA CPG, the trial by Perlman et al. (2019)(278) was highlighted. This trial of 200 individuals showed that Swedish massage improved WOMAC global scores (pain and function) in patients with KOA compared to light touch and usual care.(278) In all these studies of different forms of massage, massage had a very low risk of harm or side effects.

Meditation

We did not review any new studies of meditation treatment for OA of the knee and hip. However, we reviewed mindfulness-based interventions below and acknowledge that meditation and mindfulness are related concepts and that mindfulness meditation is a popular type of meditation practice.

Mindfulness

Mindfulness-based interventions are complementary treatments used to treat pain.(279) Mindfulness derives from the Buddhist spiritual tradition and manifests as a present-moment, nonjudgmental awareness and acceptance of one's thoughts, emotions, and experiences.(280) Mindfulness is fostered through various meditation practices that have shown to improve attention regulation, body and self-awareness, and emotional regulation.(281)

The evidence reviewed for mindfulness-based interventions for knee or hip OA included two small RCTs by Shah et al. (2024) and Marais et al. (2022).(282,283) Shah et al. (2024) compared a telehealth-delivered mindful exercise intervention (n=21) versus telehealth exercise only (n=19) in patients with KOA.(275) There were no differences between study interventions for function, pain interference, or pain severity at 8 or 14 weeks. In the trial by Marais and colleagues,(283) guided mindfulness exercises (n=20) were compared to usual care (n=20) in knee or hip OA. There were no differences between mindfulness exercises and usual care in function, pain severity, or QoL at 3 or 6 months. However, mental health improved more in the mindfulness arm at the end of treatment, yet benefits did not persist at the 6-month follow-up. Mindfulness is considered safe; there were no differences in reported SAEs between study arms.

Moxibustion

Moxibustion is a Traditional Chinese Medicine treatment that involves burning dried mugwort (moxa) on or above the skin at acupuncture points to warm meridians, stimulate Qi (energy) flow, and promote healing.(284) The burning moxa can be rolled in stick form, placed on the skin, set on acupuncture needles, or delivered by specialized machines that radiate heat.(285) Moxibustion is believed to work via heat conduction and radiation that penetrates tissue and increase blood flow as well as pharmacologically active compounds in moxa and its combustion products.(286)

A small three-arm trial by Kang et al. (2020)(287) tested electronic moxibustion (n=45), traditional moxibustion (n=45), and usual care (n=46) for patients with KOA. Results showed no differences in function, pain severity, or QoL between electronic and traditional moxibustion, yet all outcomes were improved relative to usual care. In this trial, no SAEs were reported. While considered safe, burns, allergic reactions, infection, and respiratory symptoms from smoke exposure have been reported.(284)

Mud Therapy

Mud therapy (also called peloid therapy or mud-bath therapy) is a treatment that uses mineral-rich mud often combined with high temperature, water enriched with organic and inorganic minerals that are applied to the different body parts to relieve pain, facilitate blood circulation, and improve skin conditions. Treatment typically involves 10 daily sessions for acute treatment where heated mud is applied to affected joints, often followed by mineral water baths.(288) The therapeutic mechanisms are believed to derive from hyperthermia, mechanical effects from mud application, and anti-inflammatory effects from mineral absorption.(289)

We reviewed a SR by Raza et al. (2021)(290) that included 6 RCTs and more than 500 participants with KOA. Two of the trials compared mud therapy (mud bath or mud pack) versus hot pack therapy and three of the trials compared mud therapy to usual care. Overall, mud therapy showed improved function and pain severity compared to control.

Neurofeedback

Neurofeedback is a technique to train individuals to learn to self-regulate specific patterns of brain activity through real-time feedback, typically using electroencephalography (EEG) or functional magnetic resonance imaging (fMRI).(291) Neurofeedback targets brain areas involved in pain modulation, emotional processing, and sensory components of pain (e.g. anterior cingulate cortex and somatosensory cortex).(292) Neurofeedback has been investigated for various chronic pain conditions including fibromyalgia, neuropathic pain, migraines, chronic low back pain, and KOA.(293)

A single RCT was identified and reviewed by Mathew et al. (2022)(294) for neurofeedback. In a very small trial with brief follow-up, Mathew and colleagues (294) compared 9 sessions of neurofeedback over 3 weeks in 11 participants compared to sham neurofeedback (n=10) in patients with KOA. There were no differences between study arms in functional improvement, pain interference, or pain severity. No SAEs were reported in either arm.

Additional Considerations

The Work Group also considered patient values and preferences, feasibility, and subgroup considerations. Findings from the VA/DOD Patient Focus Group indicate that Veterans and Service Members value a holistic and individualized approach to treatment of OA and associated pain.

Patient preferences likely vary for these CIH interventions. Some treatments may be preferred (e.g. massage) relative to other treatments such as acupuncture since some individuals may have anxiety related to use of acupuncture needles. Similarly, providers’ preferences may differ on whether to recommend them or not. Furthermore, clinicians may not be aware of certain treatments such as balneotherapy, moxibustion, mud therapy, and neurofeedback.

From a feasibility standpoint, several complementary and integrative therapies are available at VA medical centers and military treatment facilities. However, access to these therapies is not universal and can vary by geographic location. Some therapies such as balneotherapy, moxibustion, and mud therapy have limited (if any) availability currently for Veterans and military Service Members. For example, balneotherapy, moxibustion, and mud therapy are typically delivered in specialized spas or health resort settings rather than health care settings. Availability of these treatments also varies due to the lack of appropriately trained and skilled clinicians or practitioners.

Focus group participants reported having tried various CIH interventions and highlighted their benefits and challenges. The primary benefit mentioned was pain relief, however the relief experienced was only temporary, which was frustrating to participants. Participants also expressed the following challenges with CIH interventions; 1) transportation barriers; 2) scheduling conflicts (i.e. lack of after-hour treatment options); 3) potential out-of-pocket costs; 4) multiple visits for treatment; and 5) lengthy referral and renewal of service processes that can lead to gaps in treatment and worsening symptoms.

The Work Group systematically reviewed new and previously reviewed evidence related to this new recommendation.(256-270,272-296) Therefore, this recommendation is categorized as Reviewed, New-replaced. The Work Group’s confidence in the quality of the evidence was Low. The evidence was limited by few studies, small sample sizes, modest effects sizes, short-term follow-up, various treatment protocols, and minimal reporting of side effects. The benefits of these interventions (improved function, reduced pain interference, and pain relief) were judged to outweigh the potential harms, which were considered minimal. Patient values and preferences varied somewhat, with many expressing interest in alternative treatment modalities while also expressing concern about out-of-pocket costs and only short-term relief. The Work Group also considered the challenge that some of these therapies are delivered in specialized spas or resort settings in a few locales rather than medical settings. Thus, the Work Group decided upon a Neither for nor against recommendation.

X. Research Priorities

There are several areas that require more focused research to provide stronger evidence for further recommendation development across the spectrum of care. In summary, the Work Group recommends further research on the long-term safety, effectiveness and comparative effectiveness of interventions for OA with attention to patient subgroups, sustained outcomes, cost-effectiveness and guidance for clinical decision-making.

A. Distinguishing Pain Phenotypes to Improve Treatment Targeting in Osteoarthritis

• Nociplastic pain mechanisms are estimated to be a prominent feature in up to 40% of knee and hip OA cases, where reported pain severity is disproportionate to observable structural damage. This represents a large subgroup of patients who may respond poorly to tissue-directed treatments.(297,298) • The prevalence and clinical profile of nociplastic pain among Veterans and Active-Duty Service Members with OA is not well characterized. Research is needed to define how frequently this phenotype occurs in this population and to describe its clinical features.(299)
• Validated screening instruments exist but require feasibility testing. Research should help establish practical, mechanism-informed screening pathways to enable frontline providers to distinguish nociplastic from nociceptive pain in patients presenting with hip or knee OA, and to direct patients toward interventions most likely to address the underlying pain mechanism.(300,301)
• Mechanism-matched treatment trials are needed to determine whether phenotype-guided therapy improves clinical outcomes compared with current non-phenotype approaches.(302)

B. Long-term Studies and Comparative Effectiveness Research

• OA is a chronic condition; therefore, studies of a longer duration (>12 weeks) should be conducted to determine long-term effectiveness and safety.
• There is a paucity of research on the comparative effectiveness of different treatment options for OA of the knee and hip. Additional studies are needed to examine the comparative effectiveness of pharmacologic and non-pharmacologic options.
• Overall, limited studies address the treatment of HOA. Future studies should focus specifically on the management of HOA to better inform clinical decision-making.

C. Lifestyle-Based Interventions

• Additional studies are needed on weight loss interventions, alone or combined with other interventions, to evaluate their impact on OA outcomes.
• Exercise is a key component of OA management, but further research is needed on the comparative effectiveness of different exercise types (non-weight-bearing, weight-bearing, aerobic) and on controlling dose and loading parameters.

D. Physical Therapy

• While physical therapy is a safe and effective intervention for patients with hip and knee OA, research is needed on the long-term effectiveness (beyond 6-12 months), including sustainability of benefits, safety, and impact on healthcare cost and utilization.
• Additional research is recommended to help determine the optimal timing and strategies for the delivery of physical therapy across the disease course of hip and knee OA, including approaches to improve patient adherence and long-term engagement.
• Further studies are also recommended on how to more effectively engage patients in physical therapy interventions. Given changes in demand and healthcare utilization, studies comparing alternate modes of delivery for physical therapy should be performed comparing telehealth-supported, self-directed, group, and in-person treatment for both utilization and treatment effectiveness.

E. Devices

• While bracing appears to improve pain and function compared with usual care, its effectiveness compared with control orthoses is variable. Additional research is needed using more uniform comparators, standardized controls, and consistent protocols for wear time and activity-specific use. Long-term, high-quality comparative effectiveness studies of different brace designs and optimizing knee braces are needed.
• Further research is needed to standardize outcome measures and assess potential harms of bracing, including objective measures of functional performance, muscle strength, and muscle cross-sectional area, to better understand risks such as disuse atrophy.
• There is a paucity of well-powered comparative effectiveness studies of orthopedic insoles, with substantial heterogeneity in insole type, materials, and fabrication methods. Future studies should control for wear time, account for daily activity patterns, and identify patient subgroups most likely to benefit.
• Additional studies are recommended to evaluate the effectiveness of TENS and other electrotherapeutic devices, particularly for patients with OA and comorbidities that limit participation in exercise-based interventions.

F. Pharmacotherapy

• Given limited pharmacologic options for hip and knee OA, larger, well-designed trials with longer follow-up are needed to evaluate the efficacy, safety, and recommended delivery of capsaicin, acetaminophen, topical NSAIDs, and selective versus non-selective COX-2 inhibitors.
• Persistent gaps remain in understanding optimal use of opioids and combined pharmacotherapies. Future studies should clarify the role of buprenorphine, identify populations who may benefit from short- or long-term opioid use, and establish safe multimodal sequencing strategies while assessing opioid-related risks.
• More standardized, high-quality research is needed for intra-articular injections, including expanded outcome measures (e.g., QoL, sleep, pain interference), clearer guidance on timing, frequency, and patient selection, and evaluation of both local and systemic AEs.
• Overall, higher-quality, more standardized studies and improved clinical decision-making tools are needed, particularly for patients with comorbidities and for HOA, which remains underrepresented in literature.

G. Evidence to Support the Safe and Effective Use of Orthobiologic Therapies and Other Emerging Biologic Treatments for Osteoarthritis

• Research should prioritize standardization of orthobiologic preparation and administration, including product type, dosing, timing, frequency, and injection techniques, to reduce variability and improve comparability across studies.
• Well-designed RCTs are needed to assess the safety, effectiveness, and comparative effectiveness of orthobiologics (e.g., PRP, stem cells, amniotic products, polynucleotides) versus placebo, sham, and established injectable therapies for improving outcomes and OA progression.
• Additional studies should better define patient populations most likely to benefit, including subgroup analyses relevant to Veterans and Service Members (e.g., age, disease severity, comorbidities, prior joint injury, occupational demands), and

incorporate cost-effectiveness, implementation considerations, and patient education and shared decision-making.

H. Interventional Procedures

• Standardization of protocols and techniques is needed for procedures such as GNB, RFA, ESWT, and low-dose radiation therapy, including dosing, frequency, type, administration, and procedural parameters.
• Well-designed studies are needed to evaluate safety, effectiveness, and long-term outcomes versus sham or other non-surgical treatments, with attention to patient subgroups, hip versus knee OA, and Veteran and Service Member populations.
• Research is needed to assess long-term, patient-centered outcomes including sustained pain relief, function, QoL, and AEs, and clarify which patients are most likely to benefit from each procedure.

I. Dietary Supplements and Nutraceuticals in Osteoarthritis

• The use of OTC dietary supplements and nutraceuticals is common among patients with OA but for more robust, non-industry funded studies are needed to determine the dose, frequency, effectiveness, and safety of supplements. More rigorous evaluation of product development and purity standards would also be beneficial in clarifying their role in managing OA.

J. Complementary and Integrative Health

• Further research is needed to determine the effectiveness and role of CIH interventions for knee and hip OA, including timing, combination with other therapies, and integration into current management paradigms. Larger, well-designed trials are needed to address methodological limitations, identify optimal frequency, duration, and style, and isolate specific intervention effects.
• Long-term outcomes and cost-effectiveness remain unclear, particularly for hip OA and combination therapies, requiring further evaluation of sustained benefits, safety, and economic impact.

K. Psychological Interventions

• The WG acknowledged a limitation that this CPG did not review psychological interventions for the treatment of osteoarthritis of the knee and/or hip.
• For the next CPG update, the WG recommends including a psychologist as a participant in the Work Group development team.
• The evidence review should include the use of psychological interventions, such as CBT, ACT, and cognitive reprocessing therapy for the improvement of symptoms and function related to OA.

Appendix A: Guideline Development Methodology

A. Developing Key Questions to Guide the Systematic Evidence Review

To guide this CPG’s systematic evidence review, the Work Group drafted 12 key questions (KQs) on clinical topics of the highest priority for the VA and DOD populations. The KQs followed the population, intervention, comparison, outcome, timing, and setting (PICOTS) framework, as established by Agency for Healthcare Research and Quality (AHRQ) (see Table A‐1).

Table A-1. PICOTS (303)

Abbreviation: PICOTS: population, intervention, comparison, outcome, timing, and setting

The Champions, Work Group, and Evidence Review Team carried out several iterations of this process, each time narrowing the scope of the CPG and literature review by prioritizing the topics of interest. Due to resource constraints, not all developed KQs could be included in the systematic evidence review. Thus, the Champions and Work Group determined which questions were of highest priority to include in the review. Table A-2 contains the final set of KQs used to guide the systematic evidence review for this CPG.

a. Population(s)

The clinical population considered in this SR are adults (aged 18 years or older) with osteoarthritis of the hip and/or knee. All of the KQs focused on this overall clinical population.

b. Interventions and Comparators

c. Outcomes

d. Timing

e. Setting(s)

The standard setting for all KQs is Ambulatory care. KQ9 also includes inpatient settings.

B. Conducting the Systematic Review

Literature searches identified 6,315 citations potentially addressing the KQs of interest for this evidence review. After 94 duplicates were removed, there were 6,221 citations. Of these, 4,427 were excluded upon title and abstract review for clearly not meeting inclusion criteria (e.g., not pertinent to the topic, not published in English, published prior to the study inclusion publication date, or not a full-length article). A total of 1,794 full-length articles were reviewed. Of these, 1,685 were excluded for the following reasons: comparator not of interest (298), intervention not of interest (277), superseded by another SR (252), not a country of very high Human Development Index (HDI) (231), population not of interest (130), study design not of interest (121), publication type not of interest (99), outcomes not of interest (97), other (e.g., SR did not include risk of bias, relevant SR with no useable data, too short follow-up period [87]), study included in an included SR (35), published before January 1, 2015 (24), does not address any KQ (19), inadequate sample size (10), or not English language (5). Detailed information on inclusions and exclusions throughout the review process are provided in Figure A-1 below.

Overall, 109 publications addressed one or more of the KQs and were considered as evidence in this review, including 53 systematic reviews and 56 primary studies. Table A-2 indicates the number of studies that addressed each of the questions, with some publications being used for more than one KQ.

Algorithm or figure on page 87 of the original PDF is not reproduced here — see the original document (text descriptions of the algorithms are in the appendix, if provided).

Alternative Text Description of Study Flow Diagram

Figure A-1. Study Flow Diagram is a flow chart with nine labeled boxes linked by arrows that describe the literature review inclusion-exclusion process. Arrows point down to boxes that describe the next literature review step and arrows point right to boxes that describe the excluded citations at each step (including the reasons for exclusion and the numbers of excluded citations).

1. Box 1: 6,315 citations identified by searches.

a. Right to Box 2: 94 citations excluded as duplicates.

b. Down to box 3.

2. Box 3: 6,221 titles and abstracts reviewed.

a. Right to Box 4: 4,427 citations excluded at the title and abstract level. Citations excluded were off topic, not published in English, or published prior to inclusion date.

b. Down to Box 5.

3. Box 5: 1,794 full-length articles reviewed.

a. Right to Box 6: 1,686 citations excluded at full-article level.

i. 298 comparator not of interest.

ii. 277 intervention not of interest.

iii. 252 superseded by another SR.

iv. 231 not of very high HDI.

v. 130 population not of interest.

vi. 121 study design not of interest.

vii. 99 publication type not of interest.

viii. 97 outcomes not of interest.

ix. 87 other (e.g., study retracted, AI methods used for prediction model, inadequate follow-up period).

x. 35 included in an included SR.

xi. 24 published before January 1, 2015.

xii. 19 does not address any KQ.

xiii. 10 inadequate sample size.

xiv. 5 not English language.

b. Down to Box 7.

4. Box 7: 109 included publications (53 systematic reviews and 56 primary studies).

Table A-2. Evidence Base for KQs

*Some publications addressed more than one KQ.

Abbreviations: BMI: body mass index; CIH: complementary and integrative health; FDA: US Food and Drug Administration; KQ: key question; OA; osteoarthritis; QoL: quality of life; RCT: randomized controlled trial; SR: systematic review

a. General Criteria for Inclusion in Systematic Evidence Review

• Randomized control trials (RCTs) or SRs of RCTs published on or after June 3, 2019, to July 31, 2025.
• Studies must be published in English.
• Publication must be a full clinical study or SR; abstracts alone will not be included. Similarly, letters, editorials, research protocols, and other publications that are not full- length clinical studies will not be accepted as evidence.
• Systematic reviews must have searched MEDLINE or EMBASE for eligible publications, performed a risk of bias assessment of included studies, and assessed the quality of evidence using a recognizable rating system, such as GRADE or something compatible (e.g., the one used by the AHRQ Evidence-based Practice Centers [EPCs]). If an existing review does not assess the overall quality of the evidence, evidence from the review must be reported in a manner that will allow us to judge the overall risk of bias, consistency, directness, and precision of evidence. We will not use an existing review as evidence if we are not able to assess the overall quality of the evidence in the review. If multiple SRs address a KQ, we will select the most recent and/or comprehensive review. In many cases, we will use multiple SRs to address a single KQ, as each SR will deal with a different intervention or intervention-comparator combination.
• RCTs must have an independent control group. Randomized crossover trials will only be included if data from the first period (prior to treatment crossover) was reported separately or an adequate washout period was used.
• For KQ8, diagnostic accuracy studies and SRs of diagnostic accuracy will be included. For KQ 10 (weight loss), RCTs with pre-planned subgroup analyses, observational studies and SRs of observational studies that report on groups who did and did not lose weight will be used to address the KQ. For all other KQs, only SRs of RCTs and individual RCTs will be considered.
• Study must have enrolled at least 20 patients (10 per study group for RCTs and 20 for observational studies).
• Study must have enrolled at least 85% of patients who meet the study population criteria. If the patient population falls below this threshold but the relevant population of patients is reported separately, then that study will be included.
• To ensure applicability to the VA/DOD healthcare systems, and ensure consistency across the CPG program, inclusion of individual studies will be limited to very high Human Development Index (HDI), countries with an index ≥0.8 where standards of healthcare are comparable (e.g., United States, Canada, United Kingdom, Western Europe, Israel, Japan, Hong Kong, Australia, and New Zealand). Inclusion of the systematic reviews will be limited to those including more than half of the studies from eligible regions.

o These regions of interest are listed in Table 1 of the Statistical Annex of the

2023/24 Human Development Report produced by the United Nations Development Program.

• Study must have reported on at least one outcome of interest.

b. Key Question Specific Criteria for Inclusion in Systematic Evidence Review

For KQ8, diagnostic accuracy studies and SRs of diagnostic accuracy will be included. For KQ10 (weight loss), RCTs with pre-planned subgroup analyses, observational studies and SRs of observational studies that report on groups who did and did not lose weight will be used to address the KQ. For all other KQs, only SRs of RCTs and individual RCTs will be considered.

c. Literature Search Strategy

Information regarding the bibliographic databases, date limits, and platform/provider can be found in Table A-3, below. Additional information on the search strategies, including topic-specific search terms and search strategies can be found in Appendix F. In accordance with VA/DOD CPG methodology, evidence retrieved in prior VA/DOD systematic reviews for this topic (undertaken before the date limits noted in Table A-3) and summarized in earlier evidence reports can be brought forward to support recommendations categorized as “Not Reviewed, Not Changed,” “Reviewed, Not Changed,” or "Reviewed, Amended." See Appendix C for more information on recommendation categorization.

Table A-3. Bibliographic Database Information

d. Rating the Quality of Individual Studies and the Body of Evidence

Sigma Health Consulting assessed the methodological risk of bias of individual diagnostic, observational, and interventional studies using the USPSTF method. Each study is assigned a rating of Good, Fair, or Poor based on a set of criteria that vary depending on study design. Detailed lists of criteria and definitions appear in Appendix VI of the USPSTF procedure manual.(304)

Next, Sigma Health Consulting assessed the overall quality of the body of evidence for each critical and important outcome using the GRADE approach. This approach considers the following factors: overall study quality (or overall risk of bias or study limitations), consistency of evidence, directness of evidence, and precision of evidence. The overall quality of the body of evidence is rated as High, Moderate, Low, and Very Low.

C. Developing Evidence-Based Recommendations

In consultation with the VA Office of Quality and Patient Safety and the Clinical Quality Improvement Program, Defense Health Agency, and Sigma Health Consulting convened a 3.5 day in-person recommendation development meeting from December 2-5, 2025, to develop this CPG’s evidence-based recommendations. Two weeks before the meeting, Sigma Health Consulting finalized the systematic evidence review and distributed the report to the Work Group; findings were also presented during the recommendation development meeting (see Determining Recommendation Strength and Direction).

Led by the Champions, the Work Group interpreted the systematic evidence review’s findings and developed this CPG’s recommendations. The strength and direction of each recommendation were determined by assessing the quality of the overall evidence base, the associated benefits and harms, patient values and preferences, and other implications.

a. Determining Recommendation Strength and Direction

Per GRADE methodology, to assess the quality of the evidence base and assign a grade for the strength for each recommendation, the GRADE system uses the following four domains to assess the strength of each recommendation (88):

1. Confidence in the Quality of the Evidence

Confidence in the quality of the evidence reflects the quality of the evidence base and the certainty in that evidence. This second domain reflects the methodological quality of the studies for each outcome variable. In general, the strength of recommendation follows the level of evidence, but not always, as other domains may increase or decrease their strength. The evidence review used for the development of recommendations for osteoarthritis management, conducted by Sigma Health Consulting, assessed the confidence in the quality of the evidence base and assigned a rate of “High,” “Moderate,” “Low,” or “Very low.”

The elements that go into the confidence in the quality of the evidence include:

• Is there high or moderate quality evidence that answers this question?
• What is the overall certainty of this evidence?

2. Balance of Desirable and Undesirable Outcomes

Balance of desirable and undesirable outcomes refers to the size of anticipated benefits (e.g., increased longevity, reduction in morbid event, resolution of symptoms, improved quality of life, decreased resource use) and harms (e.g., decreased longevity, immediate serious complications, adverse event, impaired quality of life, increased resource use, inconvenience/hassle) relative to each other. This domain is based on the understanding that most clinicians will offer patients therapeutic or preventive measures if the advantages of the intervention exceed the risks and adverse effects. The certainty or uncertainty of the clinician about the risk-benefit balance will greatly influence the strength of the recommendation.

Some of the discussion questions that fall under this domain include:

• Given the best estimate of typical values and preferences, are you confident that the benefits outweigh the harms and burden or vice versa?
• Are the desirable anticipated effects large?
• Are the undesirable anticipated effects small?
• Are the desirable effects large relative to undesirable effects?

3. Patient Values and Preferences

“Patient values and preferences” is an overarching term that includes patients’ perspectives, beliefs, expectations, and goals for health and life. More precisely, it refers to the processes that individuals use in considering the potential benefits, harms, costs, limitations, and inconvenience of the therapeutic or preventive measures in relation to one another. For some, the term “values” has the closest connotation to these processes. For others, the connotation of “preferences” best captures the notion of choice. In general, values and preferences increase the strength of the recommendation when there is high concordance and decrease it when there is great variability. In a situation in which the balance of benefits and risks are uncertain, eliciting the values and preferences of patients and empowering them and their surrogates to make decisions consistent with their goals of care becomes even more important. A recommendation can be described as having “similar values,” “some variation,” or “large variation” in typical values and preferences between patients and the larger populations of interest.

Some of the discussion questions that fall under the purview of values and preferences include:

• Are you confident about the typical values and preferences and are they similar across the target population?
• What are the patient’s values and preferences?
• Are the assumed or identified relative values similar across the target population?

4. Other Implications

Other implications consider the practicality of the recommendation, including resources use, equity, acceptability, feasibility and subgroup considerations. Resource use is related to the uncertainty around the cost-effectiveness of a therapeutic or preventive measure. For example, statin use in the frail elderly and others with multiple co-occurring conditions might not be effective and depending on the societal benchmark for willingness to pay, might not be a good use of resources. Equity, acceptability, feasibility, and subgroup considerations require similar judgments around the practicality of the recommendation.

The framework below (Table A-4) was used by the Work Group to guide discussions on each domain.

Table A-4. GRADE Evidence to Recommendation Framework

D.Recommendation Categorization

1.Recommendation Categories and Definitions

For use in the 2025 OA CPG, a set of recommendation categories was adapted from those used by the United Kingdom National Institute for Health and Clinical Excellence (NICE).(93,94) These categories, along with their corresponding definitions, were used to account for the various ways in which recommendations could have been updated from the 2020 VA/DOD OA CPG. The categories and definitions can be found in Table 4.

2.Categorizing Recommendations with an Updated Review of the Evidence

Recommendations were first categorized by whether they were based on an updated review of the evidence. If evidence had been reviewed, recommendations were categorized as “New- added,” “New-replaced,” “Not changed,” “Amended,” or “Deleted.”

“Reviewed, New-added” recommendations were original, new recommendations that were not in the 2020 OA CPG. “Reviewed, New-replaced” recommendations were in the previous version of the guideline but were modified to align with the updated review of the evidence. These recommendations could have also included clinically significant changes to the previous version. Recommendations categorized as “Reviewed, Not changed” were carried forward from the previous version of the CPG unchanged.

Recommendations could have also been designated “Reviewed, Deleted.” These were recommendations from the previous version of the CPG that were not brought forward to the updated guideline after review of the evidence. This occurred if the evidence supporting the recommendations was out of date, to the extent that there was no longer any basis to recommend a particular course of care and/or new evidence suggests a shift in care, rendering recommendations in the previous version of the guideline obsolete.

3. Categorizing Recommendations without an Updated Review of the Evidence

There were also cases in which it was necessary to carry forward recommendations from the previous version of the CPG without a review of the evidence. Due to time and budget constraints, the update of the OA CPG could not review all available evidence on OA management but instead focused its KQs on new or updated scientific research or areas that were not previously covered in the CPG.

For areas of research that have not changed, and for which recommendations made in the previous version of the guideline were still relevant, recommendations could have been carried forward to the updated guideline without an updated review of the evidence. The support for these recommendations in the updated CPG was thus also carried forward from the previous version of the CPG. These recommendations were categorized as “Not reviewed.” If evidence had not been reviewed, recommendations could have been categorized as “Not changed,” Amended,” or “Deleted.”

“Not reviewed, Not changed” recommendations refer to recommendations from the previous version of the OA CPG that were carried forward unchanged to the updated version. The category of “Not reviewed, Amended” was used to designate recommendations which were modified from the 2020 VA/DOD OA CPG with the updated GRADE language, as explained above.

Recommendations could also have been categorized as “Not reviewed, Deleted” if they were determined to be out of scope. A recommendation was out of scope if it pertained to a topic (e.g., population, care setting, treatment, condition) outside of the scope for the updated CPG as defined by the Work Group.

The categories for the recommendations included in the 2025 version of the guideline are noted under the Recommendations. The categories for the recommendations from the 2020 VA/DOD OA CPG are noted in Appendix C.

E. Drafting and Finalizing the Guideline

Following the face-to-face meeting, the Champions and Work Group members were given writing assignments to craft discussion sections to support each of the new recommendations and/or to update discussion sections from the 2020 VA/DOD OA CPG to support the amended “carried forward” recommendations. The Work Group also considered tables, appendices, and other sections from the 2020 VA/DOD OA CPG for inclusion in the update. During this time, the Champions and Work Group also made additional revisions to the algorithm, as necessary.

After developing the initial draft of the updated CPG, an iterative review process was used to solicit feedback on and revise the CPG. Once they were developed, the first two drafts of the CPG were posted on the OA Wiki Website for a period of 10-15 business days for internal review and comment by the Work Group. All feedback submitted during each review period was reviewed and discussed by the Work Group, and appropriate revisions were made to the CPG.

Appendix B: Evidence Table

Table B-1. 2025 OA Evidence Table a, b, c, d

a 2020 Strength of Recommendation column: “Not applicable” indicates that the 2025 VA/DOD OA CPG recommendation was a new recommendation and therefore, does not have an associated 2020 strength of recommendation.

b Evidence column: The first set of references listed in each row in the evidence column constitutes the evidence base for the recommendation. To be included in the evidence base for a recommendation, a reference needed to be identified through a systematic evidence review carried out as part of the initial development or update of this CPG. The second set of references in the evidence column (called “Additional References”) includes references that provide additional information related to the recommendation, but which were not identified through a systematic evidence review. These references were, therefore, not included in the evidence base for the recommendation and did not influence the strength and direction of the recommendation.

c 2025 Strength of Recommendation column: The 2025 VA/DOD OA CPG was developed using the GRADE approach to determine the strength of each recommendation. Refer to the Grading Recommendations section for more information.

d Recommendation Category column: Refer to the Recommendation Categorization section for more information on the description of the categorization process and the definition of each category

Appendix C: 2020 Recommendation Categorization

¹For additional information, please refer to Evidence Quality and Recommendation Strength.

²For additional information, please refer to Recommendation Categorization and Appendix A.

³See the VA/DOD Clinical Practice Guideline for the Management of Opioid Therapy for Chronic Pain. Available at: https://www.healthquality.va.gov/guidelines/Pain/cot/

Abbreviations: DOD: Department of Defense; VA: Department of Veterans Affairs

Appendix D: Participant List

Jennifer Ault, MS, DPT, DO Service Chief Manchester VA Integrative

Kathleen Griffin, MSN, RN, FNP-C Family Nurse Practitioner, VA Long Beach

Pain Care Clinic National PMOP Project Lead: Acute Pain

Healthcare System Long Beach, CA Jason Guevara, MD Chief of Surgery, VA Fayetteville Coastal

Service (APS) and Acute Pain Service Education Program (APSEP) National PMOP Field Advisory Board Manchester, NH Matthew Bair, MD, MS Director, VA Health Systems Research

Healthcare System Fayetteville, NC Elizabeth Hall, CDR (USPHS), PharmD,

Center for Health Information and Communication Professor of Medicine, IU School of

MPH, BCPS Clinical Pharmacist, Formulary Management

Branch San Antonio, TX Michael Loncharich, Maj (USA), MD,

Medicine, Division of General Internal Medicine and Geriatrics Indianapolis, IN

Kimberlee Bayless, DNP, FNP-BC, FAANP APRN and Director, Transitional Pain

RhMSUS, FACP, FACR Rheumatology Service Chief, Walter Reed

National Military Medical Center Bethesda, MD Jiby Mathew, DNP, APRN, FNP-C Nurse Practitioner, VA Medical Center Dallas, TX Baron Moehlenbrock, Lt Col (USA), DNP,

Service, Acute Pain Service Anesthesia Department, VA George E. Wahlen Medical Center Salt Lake City, UT Gerardo Capo Dosal, Capt (USA), MD,

CAQSM Sports Medicine Physician, Mendoza Soldier

NP-C Nurse Practitioner Fort Knox, KY Ian Pace, PharmD Program Manager, VA Pharmacy Benefits

Care Clinic, William Beaumont Army Medical Center El Paso, TX Olga Carpenter, MHA, MPH, MPAS, PA-C Head, Orthopaedic/General Surgery

Management Services Temple, TX Sanjog Pangarkar, MD Physician, Pain Management West Los Angeles VA Medical Center Los Angeles, CA

Department Twentynine Palms, CA Melissa Echevarria-Baez, Psy.D. Licensed Clinical Psychologist Orlando, FL Jess Edison, Col (Ret, USA), MD Division Director, Rheumatology, USUHS

School of Medicine Bethesda, MD

Bryan Pickens, Lt Col (USA) PT, DSc,

FAAOMPT, Associate Dean, Graduate School, US Army

Medical Center of Excellence (MEDCOE) San Antonio, TX Matthew Prince, PT, DPT Clinical Specialist in Orthopedic Physical

Therapy Grand Junction, CO Aaron Salazar, Capt (USAF), DO Family Health Physician, Columbus Air

Force Base Columbus, MS Robert Wallace MS, RD Deputy Chief, Nutrition Care Division,

William Beaumont Army Medical Center El Paso, TX Jason J Weiner CDR (USN), MD, FACR,

FACP, RhMSUS Chair, Department of Medicine, Naval

Medical Center San Diego (NMCSD) Navy Rheumatology Specialty Leader Staff Rheumatologist San Diego, CA

Appendix E: Patient Focus Group Methods and Findings

A. Methods

VA and DOD Leadership recruited seven participants for the focus group with support from the Champions and other Work Group members as needed. The goal of recruitment for this Patient Focus Group was to have a group of engaging, diverse patients receiving VA or DOD healthcare services, who could cogently explain their experience with OA. Participants predominantly received care from the VA and DOD, with some individuals receiving primary care or physical therapy from a civilian provider due to scheduling or staffing constraints. The participants were primarily younger, ranging from 42-81 years old. Many of the participants were retired military personnel or Veterans but some were actively employed in other fields. Participants’ length of treatment ranged widely from as recent as 1 year to 20 years or more. Participants also mentioned engaging in lifestyle modifications such as healthier food choices, increased exercise, and mindfulness.

The Work Group, with support from Sigma Health Consulting, identified topics on which participants’ input was important to consider in developing the CPG. Sigma Health Consulting developed, and the Work Group approved, an interview guide covering these topics. The focus group facilitator who led the discussion used the guide to elicit the participants’ perspectives about their treatment and overall care. Not all questions included in the Moderator’s Guide for the OA Patient Focus Group were addressed by participants, but because the moderator encouraged conversation between the Patient Focus Group members, most topics were covered.

B. Patient Focus Group Findings

a. Participants emphasized their preference for a holistic and individualized approach to the treatment of osteoarthritis and its symptoms.

• Participants' personal characteristics (e.g., age and weight) and co-occurring conditions impacted osteoarthritis treatment.
• Participants value shared decision-making, and an individualized, "whole person" approach to osteoarthritis treatment.

b. Participants discussed the impact that their osteoarthritis symptoms and treatment have had on their quality of life.

• Participants shared daily challenges associated with their osteoarthritis symptoms and emphasized their desire to improve their quality of life.
• Participants often experienced secondary/referred pain and symptoms as a result of their osteoarthritis.

c. Participants highlighted their willingness to try a variety of oral pharmacological treatments and intra-articular injections, noting both benefits and limitations.

• Participants tried a variety of oral pharmacotherapies and intra-articular injections for the management of osteoarthritis and osteoarthritis symptoms.
• Participants felt that these interventions were effective for temporary relief but raised concerns about side effects and adherence.

d. Participants highlighted the benefits and challenges of non-pharmacological therapies including physical therapy, complementary and integrative health, and lifestyle interventions when managing osteoarthritis symptoms.

• Participants used a wide variety of non-pharmacological therapies, such as physical therapy and complementary and integrative health for the management of their osteoarthritis.
• Participants shared the challenges of non-pharmacological therapies for osteoarthritis management.

e. Participants emphasized the need for patient education and provider communication in identifying, treating, and managing osteoarthritis and its symptoms.

• Participants expressed the need for reliable patient education and resources for managing osteoarthritis.
• Participants emphasized the importance of providers listening to their concerns when discussing symptoms.

Appendix F: Literature Review Search Terms and Strategy

A. Resources Searched

Sigma’s Information Specialist searched the following databases for relevant information (see Table F-1).

Table F-1. Databases Searched

B. Search Strategies

The search strategies for bibliographic databases employed combinations of free-text keywords as well as controlled vocabulary terms including, but not limited to, the concepts detailed in Tables F-2 through F-6.

Table F-2. EMBASE and MEDLINE Search Strategy (Embase.com syntax)

Table F-3. PsycInfo Search Strategy (EBSCO syntax)

Table F-4. PubMed Search Strategy (PubMed syntax)

Table F-5. AHRQ EPC Reports Search Strategy

Table F-6. Cochrane Library Search Strategy

Query

(osteoarthritis OR "osteo arthritis" OR arthritis OR coxarthr* OR gonarthr*):ti,ab,kw

Table F-7. VA ESP Reports Search Strategy

Appendix G. Alternative Text Descriptions of Algorithm

The following outline narratively describes Module A. An explanation of the purpose of the algorithms and description of the various shapes used within the algorithms can be found in the Algorithm section. The sidebars referenced within these outlines can also be found in the Algorithm section.

Module A: Management and Treatment of Osteoarthritis of the Hip and/or the Knee

1. Module A begins with Box 1, in the shape of a rounded rectangle: “Patient presents with symptoms consistent with OA of the hip and/or knee” 2. Box 1 connects to Box 2, in the shape of a rectangle: “Confirm diagnosis, assess function, pain, define patient goals, discuss plan of care” 3. Box 2 connects to Box 3, in the shape of hexagon, asks the question: “Patient selects one or more OA Therapy Modalities? (See Sidebar 1)” a. If the answer is “Yes” to Box 3, then Box 4. b. If the answer is “No” to Box 3, then Box 2, in the shape of a rectangle: “Confirm diagnosis, assess function, pain, define patient goals, discuss plan of care” 4. Box 4, in the shape of a rectangle, “Implement individualized treatment plan” 5. Box 4 connects to Box 5, in the shape of a hexagon, asks the question: “Has patient achieved goals for pain or function?” a. If the answer is “Yes” to Box 5, then Box 6, in the shape of an oval: “Continue individualized treatment plan and follow up as clinically indicated” b. If the answer is “No” to Box 5, then Box 7. 6. Box 7 in the shape of a rectangle: “Refer to physical therapy if not previously done and/or consider next steps in care (See Sidebar 2 and Sidebar 3)” 7. Box 7 connects to Box 8, in the shape of a hexagon, asks the question: “Have treatment goals been achieved?” a. If the answer is “Yes” to Box 8, then Box 6, in the shape of an oval: “Continue individualized treatment plan and follow up as clinically indicated” b. If the answer is “No” to Box 8, then Box 9, in the shape of a rectangle with bulleted list:

i. Reassess diagnosis ii. Refer to surgical consultation and obtain weight-bearing plain radiographs if not previously done in the past 6 months (see Appendix K)” 8. Box 9 connects to Box 2, in the shape of a rectangle: “Confirm diagnosis, assess function, pain, define patient goals, discuss plan of care”

Appendix H. Patient History and Physical Examination

A. Knee and Hip Osteoarthritis Risk Factors

Evidence shows that age, elevated BMI, and prior history of injury to a joint are all independent risk factors for development of OA of the knee and hip.(6,306,307)

High BMI is a well-established modifiable risk factor for OA and the growing global impact of high BMI on OA burden is significant. There is a profound need to implement targeted obesity prevention as a global public health strategy to mitigate the rising burden of BMI-related OA.(306)

Although, the risk of developing KOA after a knee injury is about sixfold compared to others without, not all patients who sustain these injuries will develop the symptoms of OA.(308) In particular, the highest risk for development of OA is found after cruciate ligament injury, meniscal tear, and intra-articular fracture.(309)

Similarly, although age is one of the strongest risk factors for development of OA of all the joints, some patients will not develop OA as they age.(6) The increase in both the prevalence and incidence of OA with age is understood to be multifactorial due to a combination of both cumulative exposure to various risk factors and biological changes that occur with aging, and yet genetics clearly also plays a role.(113)

There is an abundance of data to support that, in addition to age, prior injury, and increased BMI, there is a strong genetic component in OA, particularly in the hip. Genetic variants in cartilage structural genes may play a role in early onset of OA and there are many genetic variants that have been identified through a genome-wide association study (GWAS) and majority of these genes are related to regulation of DNA transcription.(310) In fact, studies estimate that the genetic contribution to OA is significant, ranging from about 35% to 65%, with an average around 50%. However, this genetic influence can vary depending on the affected joint, with higher heritability for hip and hand OA compared to KOA.(311,312)

The prevalence of KOA has been shown to be greater in females.

The increased risk for radiographic and symptomatic OA in women may be linked to a range of hormonal, immunomodulatory, anatomical, and lifestyle factors.(313)

Knee misalignment can lead to OA by causing abnormal stress on the joint, which can accelerate the wear and tear of the cartilage. Both genu valgus and varus alignment can result in uneven loading over time and either premature onset of OA or faster progression of OA.(314,315)

Anatomic hip joint abnormalities can also cause OA, particularly when they lead to abnormal joint loading and wear on the cartilage. These abnormalities include conditions like hip dysplasia, femoral acetabular impingement, and slipped capital femoral epiphyses.(316-318)

The relationship between physical activity and risk of development of OA depends on the type of activity and certain risk factors that can increase vulnerability. Although total physical activity is not associated with increased risk, there are some specific types of high-intensity or high- impact activity that might pose a risk for individuals with certain preexisting conditions such as previous knee injury, low muscle mass, or obesity.(319) Weight bearing recreational physical activity is associated with increased risk of development of KOA, amongst those with low levels of lower limb muscle mass.(319) Recreational sport activity has not been found to cause OA and in fact, it may be protective.(320)

There are occupational risk factors for the development of KOA due to biomechanical stressors placed on the knee joint. These risk factors include physically demanding jobs that involve heavy lifting, frequent kneeling, squatting, prolonged standing, regular stair climbing, vibration, and unnatural body positioning.(38,321) Agricultural workers, construction workers, carpenters, plumbers, machine operators, miners, floor and brick layers, and metal workers are all examples of high-risk occupations.(38) Occupations with high physical workload can also increase the risk of developing HOA. In fact, lifting, carrying heavy loads, demanding postures, repetitive activities, long standing and running, as well as exposure to body vibrations are all associated with increased risk.(322) Rates of OA have been reported to be significantly higher in military populations than in comparable age groups in the general population.(12)

C. Knee Osteoarthritis Patient History

According to researchers, the main symptoms of KOA include activity-related pain often eased with rest, swelling, a grating or grinding sensation with movement, and loss of flexibility.(34)

The joint pain of OA is often described as worse with activity and relieved by rest. In advanced OA, there may be rest or night pain which can lead to sleep disruption. The quality of pain is deep and aching and it can be local or diffuse. Patients may also note stiffness, crepitus, reduced range of motion, swelling, and/or joint instability, buckling, or giving way. The pain may be exacerbated with certain activities of daily living that stress the joint such as standing, squatting, kneeling, walking, and stair climbing.(34)

a. Knee Osteoarthritis Physical Examination

In the physical examination of symptomatic KOA, it can be helpful to include an assessment of BMI, presence of crepitus within any knee compartment, joint line tenderness, frontal plane alignment as compared to sagittal, active and passive range of motion of the knee, lower limb strength (especially in the knee flexors and knee extensors), joint proprioception, tenderness, present of an effusion, and varus or valgus laxity of the knee.(323,324) Joint instability, described as giving way or a buckling sensation, is commonly reported with KOA, and therefore, more advanced ligamentous examination maneuvers may be indicated depending on the individual patient's circumstances. Bony enlargement findings on physical examination are highly specific for establishing a diagnosis of KOA (SP 95%), whereas crepitus is sensitive (SN 89%).(325)

Patients with KOA may also exhibit various gait impairments, which are easily observed. Gait impairments are thought to lead to abnormal joint loading during ambulation. Moreover, gait impairments may lead to slower ambulatory speeds, shorter strides, lower foot strike, and decreased lumbar motion, creating unsafe conditions and increasing the risk of falls.(326) There is an increased odds of medial tibiofemoral OA progression with greater baseline peak knee adduction movement.(327,328) Therefore, an assessment of balance and fall risk should be considered in patients with KOA.

D. Hip Osteoarthritis Patient History

Patients with HOA present most often with complaints of groin or anterior thigh pain with activity or weight-bearing but can progress eventually to pain at rest. Providers should be aware that hip pain can be referred pain to the buttock, the knee, and even below the knee.(329) Historical features associated with HOA included a family history of OA, a personal history of KOA, and pain on climbing stairs or walking down slopes.(330-332) Although infrequently reported, in patients complaining of worse pain located in the medial thigh, it was highly specific for HOA (SP 98%).(330) Patients <60 years of age are less likely than older patients to have HOA. Additionally, the absence of morning stiffness <60 minutes, pain in walking, or pain improved on sitting identified patients as less likely to have HOA.(330)

Providers should inquire about occupational history, prior hip injuries, history of OA at other sites, family history of OA, activity participation, pain history, and functional impairments. Patients may complain of pain with squatting and stair climbing. Sitting may be uncomfortable, specifically if the hip is placed in excessive flexion. Patients often lean away from the involved hip in a seated position and attempt to reduce the degree of required hip flexion.(333) Although the classic complaint of patients with HOA is groin pain, the patients may localize their pain by placing their ipsilateral thumb in their groin with their hand and fingers cupping their greater trochanter and buttocks forming the “C sign.”(333) The pain experienced by the patient can be stabbing, sharp, or dull. Similar to KOA, the hip becomes increasingly stiff as the disease progresses, and patients frequently report stiffness after a period of inactivity.

a. Hip Osteoarthritis Physical Examination

Examination of the patient with HOA should assess BMI, passive range of motion (particularly internal rotation, flexion, and abduction), gait, balance, and lower limb muscle strength (particularly the hip abductors and hip flexors). An assessment of the lumbar spine or sacroiliac joint may be warranted.(329) With HOA, the motion of the hip can become progressively restricted secondary to synovitis, soft tissue contractures, and loss of joint congruency. Examination may reveal a flexion contracture or reduced internal rotation, flexion, and abduction.(329,334) Patients with a painful hip often stand with the hip and knee slightly flexed to relax the hip joint capsule.(333) Abnormal gait patterns include a winking gait with excessive pelvic rotation in the axial plane, an abductor-deficient gait, an antalgic gait with a shortened stance phase on the painful side, or a short leg gait with dropping of the shoulder in the direction of the short leg.(335)

In general, examination findings are more valuable and helpful compared to historical features. Strongly associated physical findings for HOA include posterior hip pain with squatting, groin pain with hip abduction or adduction, abductor weakness, decreased hip adduction, and decreased internal rotation, as measured by a goniometer or compared with the contralateral leg.(330) The presence of normal hip passive adduction or abduction were the most useful in identifying patients who are less likely to have HOA.(330) HOA is strongly associated with the presence of 4 or more or the following: >60 years of age, pain lasting longer than 3 months, groin tenderness, decreased external rotation, and absence of pain aggravation by sitting (positive likelihood ratio of 4.9).(330,336) There is a lack of evidence for the use of any special test in the context of predicting early HOA.(337-339)

Appendix I. Pharmacotherapy

Chronic Pain in Veterans – Sensibly Selecting OA Pharmacotherapy

Chronic pain is highly prevalent among U.S. Veterans and is a leading cause of disability, with musculoskeletal conditions such as OA and back pain being especially common. However, the degree of pain and functional impairment often far exceeds what would be predicted by imaging or physical findings alone. This discordance is well-documented: studies consistently show a weak correlation between radiographic severity of OA and reported pain or disability, underscoring that tissue pathology is only one component of the pain experience.(298,302,340,341) Of critical importance is that pharmacotherapy, and in fact any joint specific intervention, is unlikely to be effective if non-tissue pathologies (e.g. psychosocial lesions) are the driving force behind a Veteran or Active-Duty Service Member’s pain and pain related disability. It is estimated that up to 40% of patients diagnosed with OA-related pain actually have a centralized pain process predominating (i.e. nociplastic pain) and these estimates may be higher in U.S. Veterans and Service Members, especially those who are younger.(300,342) As such, determining whether a pain/pain impairment is nociceptive versus nociplastic is an imperative first step before selecting any relief inducing intervention, including pharmacotherapy. (See Algorithm)

Chronic primary pain syndromes (nociplastic pain) are characterized by pain that persists or recurs for more than three months, is associated with significant emotional distress or functional disability, and is not fully explained by another diagnosis or the degree of tissue damage. In Veterans, this phenotype is common, especially when pain is widespread, disproportionate to imaging findings, or accompanied by symptoms such as fatigue, sleep disturbance, cognitive dysfunction, or mood disorders.(298,302,341,343) Central sensitization, where the nervous system amplifies pain signals, plays a key role, and risk factors include prolonged pain exposure, comorbid psychological conditions, and prior trauma.(302,341)

Distinguishing nociplastic from nociceptive pain is critical for effective management. Nociplastic pain is less responsive to peripherally targeted interventions (e.g., NSAIDs, injections, surgery) and instead requires a shift toward biopsychosocial strategies. These include patient education, CBT, graded exercise, and multidisciplinary rehabilitation, all of which have demonstrated benefit in improving function and QoL.(298,302,340,344,345) Opioids and invasive procedures should be avoided unless other strategies have failed and risks are carefully weighed, as they offer limited benefit and substantial harm in this population.(298,302,342,346)

Clinical assessment should focus on:

• Comprehensive pain history (onset, distribution, quality, impact on function) • Associated symptoms (fatigue, sleep, mood, cognitive complaints) • Physical exam to rule out other causes but avoid over-reliance on imaging • Use of validated tools (e.g., Central Sensitization Inventory) to identify central features (298,341)

When a chronic primary pain syndrome is expected to be the prominent driver of emotional, physical, or social impairment, a treatment strategy which focuses on explaining how the current state developed and focuses on functional recovery with only judicious use of joint/tissue directed or pain-relieving interventions should be employed (see Table I-2). Reserve anti-nociceptive and anti-inflammatory interventions (see Table I-3) for when a secondary pain process is more likely than not.

In summary, secondary pain due to joint specific OA responds well to anti-nociceptive pharmacologic interventions (see Table I-4). However, primary care providers should maintain a high index of suspicion for chronic primary (nociplastic) pain in Veterans and Active-Duty Service Members with pain and disability out of proportion to age-related OA findings. Early recognition and a shift to evidence-based, multidisciplinary, biopsychosocial management are essential to improve outcomes and reduce unnecessary interventions.(298,302,340,341) The VA/DOD Management of Chronic Multisymptom Illness (CMI) CPG is an additional resource to assist clinicians caring for patients with medically unexplained pain. (See VA/DOD Management of Chronic Multisymptom Illness CPG)

Table I-1: Features to assess for primary pain syndrome versus nociceptive/ inflammatory pain process

Abbreviations: NSAIDs: non-steroidal anti-inflammatory drugs

Table I-2: Conceptual approach to chronic pain management in patients with Chronic Primary Pain (i.e. nociplastic pain)

Table I-3: Pharmacotherapy Treatment Selection in Hip/Knee OA and OA-Related Pain

Initial Assessment Confirm OA diagnosis (hip or

Assess comorbidities (GI, CV,

Initiate Non-Pharmacologic

knee)

renal)

Ineterventions

Hip/Polyarticular OA: Oral NSAIDs or Acetaminophen

Adequate Reponse

• Yes: Continue current management • No: Consider re-evaluation to
• Avoid topical NSAIDs for hip OA Monitor Response and Side

Knee OA: Topical NSAIDs or

specifically include consideration for a primary pain syndrome and psychosocial conttributiors. If absent, proceed.

capsaicin preparations

Effects

Intra-articular corticosteroid injections (knee or image-guided

Second-Line / Adjunctive

Viscosupplementation (knee

Oral Duloxetine (especially for

Pharmacotherapy

only)

knee OA)

hip)

Inadeqaquate Reponse/Persistent Severe Pain

Surgical Referral

• Refer for persistent, severe pain

despite optimal non-surgical management

• No: Continue current management • Yes: Consider re-evaluation to

Avoid opioids (including

Monitor Response and Side

tramadol)

Effects

specifically include consideration for a primary pain syndrome and psychosocial conttributiors. If absent, proceed.

Ongoing Re-evaluation

• Monitor pain, function, medication

tolerance • Adjust medications, reinforce non- pharmacologic strategies • Do NOT initiate opioids without

multi-disciplinary pain specialty support

Abbreviations: CV: cardiovascular; GI: gastrointestinal; NSAIDs: non-steroidal anti-inflammatory drugs; OA: osteoarthritis

Table I-4: Commonly Used Pharmacologic Agents for the Treatment of OA and their Selected Characteristics a ,b,c

a Refer to VA or DOD formularies for availability of agents or comparable agents. Select oral NSAIDs were chosen based on their relative utilization within the VA and DOD systems. The list of available formulations is not all-inclusive, and combination products are not included in Table F-1.

b For additional details on warnings and precautions, drug-drug interactions, adverse events, dosing considerations and use in special populations, etc., refer to the prescribing information for the individual agents of interest. c All NSAIDs have the potential to increase the risk for cardiovascular events and therefore should be used at the lowest effective dose for the shortest possible duration. Use with caution or avoid use of NSAIDs in patients with renal impairment, history of gastrointestinal bleeding, uncontrolled hypertension, congestive heart failure, advanced liver diseases, at high risk for or with known CVD, patients receiving anticoagulants or systemic corticosteroids, etc. Abbreviations: BID: twice a day; CrCl: creatinine clearance; CV: cardiovascular; CVD: cardiovascular disease; DOD: Department of Defense; EC: enteric-coated; g: gram(s); GI: gastrointestinal; mg: milligram(s); ml: milliliters: min: minute; NSAIDs: non-steroidal anti-inflammatory drugs; OA: osteoarthritis; QD: once a day; QID: four times a day; TID: three times a day; VA: Department of Veterans Affairs; XR: extended release

Appendix J. Nutraceuticals and Dietary Supplements

The 2025 systematic evidence review examined 16 nutraceuticals and dietary supplements: avocado and soybean extract, boswellia serrata extract, cannabidiol (CBD oil), chondroitin, curcumin, collagen, glucosamine, glucosamine plus chondroitin, MSM, omega-3 fatty acids, pycnogenol (pine bark), rosehip, traditional Chinese medicine, vitamins D and E, and willow bark extract. The Work Group’s recommendations regarding nutraceutical and dietary supplements can be found in Recommendations 29 and 30. Additional information is below.

Avocado and Soybean Unsaponifiables (ASU)

An SR by Liu et al. (2018) compared the efficacy and safety of ASU in five RCTs for patients with hip and knee OA.(245) The study found significant effects for reduction of pain and improvement in function at a dose of 300 mg/day compared to a placebo in the short- (<3 months) and medium-term (4-6 months). No clinically significant effects for pain reduction or improvement of function were reported in the long-term (>6 months) when compared to a placebo. Evidence suggests a low level of harm from the use of ASU. Current clinical evidence supports ASU 300 mg daily as a safe and moderately effective adjunct therapy for knee and hip OA, with short-term (8-12 weeks) improvements in pain and function and potential long-term (6-12 months) durability of benefit.(354,355) ASU can be integrated into multimodal OA care alongside exercise, physical therapy, and weight optimization. Continued research is warranted to confirm its long-term structure-modifying potential and identify patient populations most likely to benefit.

Boswellia Serrata (BS) Extract

Clinical evidence supports the use of BS as a safe and effective adjunct therapy for managing KOA and HOA. Multiple randomized, placebo-controlled trials and meta-analyses have shown that standardized BS extracts-particularly those enriched with 3-O-acetyl-11-keto-β-boswellic acid (AKBA) produce significant reductions in pain (VAS) and functional limitation (WOMAC) compared with placebo. Doses ranging from 100-250 mg/day to 300-600 mg/day demonstrated clinical improvement within 2-4 weeks, with maximal benefit by 8-12 weeks and sustained effects over 3 months. Across all studies, BS was well tolerated, with only mild GI or topical irritation reported and no SAEs.(356-358)

Cannabinoid (CBD) Products

Cross-sectional study by Deckey et al. (2021) evaluated the prevalence and perceived effectiveness of CBD products in 200 consecutive patients with symptomatic hip and/or knee OA. Among these patients (80 HOA, 108 KOA, and 12 both), 24% (48/200) reported CBD use. CBD users most commonly used oral tinctures (43%) or topical applications (36%). Outcomes were measured using SANE and VAS scores. CBD users reported significantly lower baseline SANE scores (m= 41.3) compared with non-users (m= 50.8; p= 0.012), indicating no perceived benefit and potentially worse pain or function among CBD users. No significant improvement in VAS or SANE outcomes was associated with CBD use compared to non-use. Additionally, 8% of participants reported marijuana use for OA-related pain. Based on current evidence, CBD products cannot be recommended as an effective adjunct for managing pain or function in hip or knee OA.(359) In contrast evidence from the exploratory cross-sectional study by Frane et al.(2022) and the Cannabis for Osteoarthritis (CANOA) double-blind, randomized, placebo- controlled trial by Mojoli et al. (2025) supports the cautious use of CBD as a safe and potentially effective adjunctive therapy for managing pain and functional limitations in knee and hip OA.(360,361) Observational data suggest that patients using CBD report improvements in pain, physical function, sleep, and overall QoL with minimal adverse effects and reduced reliance on NSAIDs and opioids, while RCT evidence in KOA confirms that a standardized CBD-rich cannabis sativa oil is well tolerated and associated with clinically meaningful symptom improvement compared with placebo. Collectively, these findings indicate that CBD may be reasonably incorporated as a non-opioid, adjunctive option for selected patients with knee or hip OA who have persistent symptoms or limited tolerance to conventional therapies, provided it is used in pharmaceutical-grade formulations, initiated at low doses with careful titration, and monitored closely, while recognizing that current evidence supports symptom relief rather than disease modification and that further long-term studies are needed.(362,363)

Chondroitin, Glucosamine, and Glucosamine plus Chondroitin

Treatment with chondroitin, glucosamine, and combination of chondroitin/glucosamine did not show improvement in pain in patients with OA of the hip and knee.(245,364-367) This CPG’s systematic evidence review yielded 10 studies with a patient pool of approximately 10,000. The confidence in the quality of evidence was low. Studies that revealed a statistically significant difference for chondroitin, glucosamine, and their combination were sponsored by industry and permitted the use of oral NSAIDs as a rescue drug or concomitantly.(367) Studies without industry involvement failed to show any clinically significant difference in pain. In a meta-analysis by Zhu et al. (2018), chondroitin showed more GI AEs, while other studies on glucosamine or combination did not show statistically significant AE rates.(364) Wide dose ranges and dosing frequency variations were noted among the studies, with dose ranges from 800-2,000 mg per day at different dosing intervals.(367) Multiple high-quality SRs and RCTs demonstrate inconsistent and clinically insignificant improvements in pain and function compared with placebo. Any observed benefit is small and unlikely to meet minimal clinically important differences. Therefore, clinicians should not routinely recommend glucosamine, chondroitin sulfate, or their combination for the management of knee or hip OA.

Curcumin

Recent RCTs demonstrate that curcumin is an effective and safe adjunct for managing knee and hip OA symptoms. Typical effective daily doses range from 500 mg twice daily (≈1,000 mg/day) of standardized extracts to 1,500-2,000 mg/day of conventional curcuminoid formulations, though newer phytosome or water-dispersible complexes achieve similar efficacy at lower doses. A high- quality RCT using Curcugen® (500 mg twice daily for 8 weeks) showed significant improvements in KOOS pain, numeric pain scores, and functional tests (TUG, 6MWT) compared with placebo, along with reduced rescue analgesic use (p ≤ 0.01). A Bayesian NMA of 23 RCTs reported curcumin significantly reduced pain (VAS MD ≈ -1.63 on a 0-10 scale) and improved WOMAC total scores (MD ≈ -18.9) compared with placebo, with lower AE rates than NSAIDs. Across multiple recent RCTs, curcumin consistently demonstrated superior pain and function outcomes (VAS, WOMAC, KOOS) versus placebo, with moderate effect sizes. When compared with NSAIDs, curcumin achieved comparable symptom relief but with fewer GI and systemic side effects. Combination therapy (curcumin + NSAID or curcumin + chondroprotective agents) may further enhance efficacy while reducing the need for rescue medications.(362,363,368) Clinicians may consider curcumin formulations as an adjunctive therapy for short-term symptom relief in patients who express interest in nutraceutical use. Evidence is strongest for KOA, with limited data in HOA.

Collagen

In a meta-analysis by Garcia-Coronado et al. (2019), collagen-based supplements significantly improved pain as measured by VAS, but not WOMAC when compared to a placebo.(246) The follow-up times were 10-48 weeks.(246) There was various collagen sources tested and doses across studies included in the meta-analysis. Two of the trials utilized a chicken collagen hydrolysate-based supplement. The remaining three trials utilized chicken undenatured type II collagen, porcine/bovine collagen peptides, and porcine/bovine collagen hydrolysate. Collagen daily doses range from 2g (one trial), 10g (three trials), and 40g (one trial). No statistically significant differences were reported between groups for AEs in an SR by Liu et al. (2018) with one RCT included with 10 g/day of collagen hydrolysate as the intervention.(245) Evidence regarding collagen supplementation is inconsistent and derived from small, short-term trials. While some studies suggest modest pain improvement, overall data are insufficient to support routine use; therefore, no recommendation for or against the routine use of collagen supplements in knee or hip osteoarthritis.

Methylsulfonylmethane (MSM)

Evidence from three RCTs in an SR by Liu et al. (2018) lasting <3 months indicated MSM significantly improved pain and function compared to a placebo.(245) Limited evidence from one small RCT (n=25) in the treatment arm showed no significant difference between MSM and placebo for any AEs.

Recent clinical evidence supports the potential use of MSM as a safe adjunct in the non-surgical management of knee and hip OA, though data remains limited and primarily short term. A randomized, double-blind, placebo-controlled trial by Toguchi et al. (2023)(237) evaluated 2,000 mg/day of MSM for 12 weeks in adults with mild knee pain and reported statistically significant improvement in the Japanese Knee Osteoarthritis Measure (JKOM) total score compared to placebo, with notable reductions in pain during standing and morning discomfort. Participants tolerated MSM well, and no treatment-related AEs were observed, underscoring its short-term safety and efficacy profile.(237) Similarly, SR and NMA by Sumsuzzman et al. (2023)(369) found that glucosamine-based combinations containing MSM (1.5-3 g/day) provided greater pain relief than placebo or glucosamine alone, based on VAS and WOMAC scores, suggesting synergistic effects when MSM is used as part of a multi-ingredient regimen. The analysis ranked MSM- containing formulations among the most effective complementary interventions for short-term OA symptom relief, though heterogeneity in formulation and trial quality limits generalizability. Across these studies, MSM demonstrated consistent short-term improvements (8-12 weeks) in pain and function, with mild GI side effects being the most common AEs. Available studies are limited by small sample sizes, short durations, and inconsistent outcomes. Current evidence does not support routine clinical use.

Omega-3 Fatty Acids

A 2022 multicenter, double-blind, randomized, placebo-controlled trial by Stonehouse et al. (2022) (370) evaluated the efficacy and safety of krill oil supplementation in adults aged 40-65 years with mild to moderate KOA. A total of 235 participants were randomized to receive either 4 g/day of krill oil (providing approximately 0.60g eicosapentaenoic acid [EPA], 0.28g docosahexaenoic acid [DHA], and 0.45g astaxanthin daily) or a placebo of mixed vegetable oil for 6 months. Outcomes were assessed using the WOMAC for pain, stiffness, and physical function, normalized to a 0-100 scale. At 6 months, krill oil significantly increased the Omega-3 Index compared with placebo (8.9% vs 5.4%, p< 0.001). Participants receiving krill oil demonstrated greater improvements in WOMAC pain (MD -5.18; 95% CI, -10.0 to -0.32; p= 0.04), stiffness (MD -6.45; 95% CI, -12.1 to - 0.9; p< 0.05), and physical function (MD -4.67; 95% CI, -9.26 to -0.05; p< 0.05) compared to placebo. Both groups improved overall, but the krill oil group achieved clinically meaningful symptom reduction over time. No significant differences were observed between groups for NSAID use, serum lipid profiles, inflammatory markers, or safety indicators, confirming good tolerability of the supplement. Clinical benefit typically emerges after 3-6 months of continuous use. Krill oil appears safe and well tolerated, without significant metabolic or inflammatory adverse effects. It should be used alongside standard non-pharmacologic and pharmacologic OA management strategies.(370)

Pycnogenol (Pine Bark)

Two RCTs in a SR by Liu et al. (2018) lasting <3 months suggest that pycnogenol (pine bark) significantly improved function compared to a placebo.(245) At three months, no AEs were reported in one small RCT (n=100).

Rosehip

There is limited evidence regarding the efficacy of rosehip compared to placebo for pain or AEs. One small RCT (n=90) by More et al. (2017), using a proprietary blend Rosaxan (MA212: 20g R. canina L.ripe fruit puree, 4g R.canina L.ripe fruit juice concentrate, 160mg U. dioica L. leaf dry extract [nettle], 108mg H. procumbens root dry extract [devil’s claw]) at a dose of 40ml/day, reported statistically significant improvement in pain as measured by the WOMAC at six and 12 weeks and no significant difference in AEs at 12 weeks.(247) Of note, the intervention group received several active ingredients in addition to the Rosaxan (MA212), including vitamin D (200 international units [IU]) and R. canina.

Traditional Chinese Medicine

Evidence from one small RCT by Lao et al. (2015) suggests no statistically significant differences between traditional Chinese medicine and placebo for pain at 2 or 8 weeks.(248) No differences were also reported by a second small RCT by Hua et al. (2013) at the 12- and 16-week follow- up.(249) The risk of AEs reported across two RCTs was low. There was variation in the supplements included under the umbrella term “traditional Chinese medicine.” The dosing of Huo- Luo-Xiao-Ling-Dan used in the Lao et al. (2015) study included 10 capsules per day (4,000 mg/day) during the first two weeks and 14 capsules per day (5,600mg/day) for the next six weeks of a blend of 11 herbs.(248)

Vitamin D

Evidence on vitamin D supplementation for knee and hip OA remains mixed but suggests potential benefit for patients with baseline deficiency. In RCT trial, Wang et al. (2023) found that monthly 50,000 IU vitamin D (1,667 IU/day) over two years did not significantly change OA symptoms overall, but those maintaining vitamin D sufficiency had modest improvements in WOMAC pain and function compared with placebo.(371) Jin et al. (2023) and Zuo et al. (2024) (372,373) similarly observed symptom relief in deficient or male subgroups, while Georgescu et al. (2024)(374) concluded benefits are limited to selected populations. Doses across recent trials ranged from 2,000-4,000 IU/day or 50,000 IU monthly, and supplementation was safe and well tolerated with minimal adverse effects.(372,374,375) Overall, vitamin D repletion is reasonable for deficient OA patients, but routine supplementation in all OA cases shows no clear advantage over placebo.

Vitamin E

A RCT by Tantavisut et al. (2017) indicated a statistically significant improvement in pain and function at two months,(250) but, according to an SR and meta-analysis conducted by Liu et al. (2018), this improvement was not evident at greater than four months.(245) Although Tantavisut et al. (2017) showed no significant AEs at two months,(250) there is evidence outside the systematic evidence review that vitamin E at higher doses (i.e., ≥400 IU/day) may lead to significant increases in bleeding, prostate cancer, and all-cause mortality.(376) Of note, the SR and meta-analysis by Liu et al. (2018) and the RCT by Tantavisut et al. (2017) included trial doses of 400 IU and 500 IU of vitamin E daily.(245,250) The recommended dietary allowance (RDA) of vitamin E for most adults is 22.4 IU.(376)

Willow Bark Extract

Evidence from two RCTs in one SR by Liu et al. (2018) lasting <3 months suggests no statistically significant difference between willow bark extract (680 mg, twice a day [BID]) and placebo for pain, function, or AEs.(245)

Appendix K. Referrals for Surgical Consultation

Referral for surgical consultation in patients with OA of the hip and/or knee is done when non- operative conservative treatments such as activity modifications, medications, physical therapy, and bracing fail to adequately control pain or correct deformity, resulting in significant impairment of QoL. Constant pain that frequently wakes up the patient despite NSAIDs, injections, and therapeutic modalities is a strong indication that surgical intervention may be needed. Functional limitations include reduced mobility and requiring ambulatory aides to walk safely. Inability to get up from a chair or climb stairs can severely impact independent living. Radiographs that demonstrate progressive OA (decreased joint space or even bone on bone) and correlate to symptoms will benefit from surgical consultation. It is essential that the patients are medically stable and are willing to proceed with surgery.

When radiographs show that HOA deformities have progressed to include large rim osteophytes, central protrusion, or collapse of the acetabulum these are indications that surgery should be done to preserve as much of the native anatomy. Similarly in KOA, varus alignments predispose to a depression and collapse of the medial tibial plateau and in valgus knees the lateral femoral condyle is often affected. When knee deformity becomes pronounced, conservative measures are frequently ineffective. Additionally, PFJ OA can interfere with the ability to rise from a sitting position or climb stairs. This approach helps maintain joint function and reduces the risk of complications associated with more extensive reconstructions.

The Work Group suggests providers obtain plain radiographs (preferably weight bearing for knees) within six months of referral for surgical consultation. This appendix is based on a recommendation in the 2014 and 2020 VA/DOD OA CPG. This was added as an appendix rather than a recommendation because the Work Group could not find high quality evidence meeting the GRADE criteria in the literature to support this as a recommendation. However, the Work Group would like to highlight that this is standard clinical practice and therefore it is important to include in this CPG. The value of weight-bearing and non-weight-bearing radiographs in the determination of osteoarthritis of the knee was compared by Gaur et al. (2024) and Bisht et al. (2024).(377,378) These studies demonstrate the importance of a weight bearing radiograph of the knee when determining the KL determination and overall assessment of OA. Weight bearing radiographs help to see the amount of joint space remaining during physiological loads. The Work Group felt additional studies were needed to make any specific recommendation regarding weight-bearing versus non-weight-bearing radiographs in the overall evaluation to determine the need for surgical consultation.

Providers may also consider that some patients may not be candidates for surgery given their medical comorbidities. Patients should be medically optimized to reduce complications prior to surgical consultation.

CV conditions such as severe coronary artery disease, heart failure, or recent stents will require cardiac clearance. In addition to CV risks, metabolic conditions such as diabetes and obesity also play a significant role in surgical outcomes. Patients with poorly controlled diabetes with a glycated hemoglobin test (A1C) above 7.5 will have an increased risk for infections and wound complications, and obese patients with a BMI above 40 may benefit from a weight management program to prevent a higher risk of complications from surgical interventions (see Management of

Type 2 Diabetes Mellitus CPG and Management of Adult Overweight and Obesity). Smoking cessation is encouraged to prevent wound healing complications (see Tobacco Use Treatment CPG). For total joint implants, smoking may impair the ingrowth of cementless components. Patients with an active infection, such as a urinary tract infection, should be treated before surgery. Those on anticoagulation need assessment to determine if their medication can be safely stopped or if bridge therapy is required for safety. Nutritional deficiencies are best managed prior to surgical referral.

Appendix L: Osteoarthritis Education

Nonpharmacologic Approaches for Knee and Hip Osteoarthritis

This section outlines nonpharmacologic management strategies for patients with knee and hip OA. It is intended to assist clinicians in implementing comprehensive patient education and lifestyle interventions, which are foundational components of OA care.

a. Patient Education and Self-Management

Effective management begins with patient education. Physicians should communicate that OA is a chronic, progressive condition that benefits from active self-management. Key points include:

• Explaining the pathophysiology and natural history of OA.
• Emphasizing the importance of lifestyle modifications, and that exercise does not cause more ‘wear and tear’ and is a healthy component of managing their OA symptoms.
• Reinforcing that nonpharmacologic strategies can significantly reduce pain and improve function when implemented appropriately.(379)

b. Weight Management

Given the biomechanical impact of excess weight on joint loading, particularly in the knees and hips, clinicians should prioritize weight management. Current evidence indicates that:

• Even a modest amount of weight loss (5-10% of total body weight) can substantially decrease pain and improve joint function in patients with overweight and obesity.
• Referral to a dietitian or weight management program may help facilitate sustained weight reduction.(379)

c. Exercise Prescription

Structured, individualized exercise programs are core to conservative OA management. Clinicians should recommend:

• Aerobic activities such as walking, swimming, or cycling are based on discussion with patients regarding preferences and pain tolerance.
• Local strengthening exercises targeting quadriceps, hip abductors, hip extensors, hamstrings and calf muscles.
• Flexibility exercises to maintain or improve range of motion.(380)

d. Joint Protection and Activity Modification

• Physicians should instruct patients in joint protection techniques, including:
• Consideration of utilization of assistive devices (e.g., cane, braces as recommended by their provider) to offload affected joints.(379)

e. Supportive Therapies and Resources

Participation in physical therapy should be encouraged for supervised exercise and joint protection strategies. Recommend educational resources, such as community-based programs and support groups, to reinforce self-management behaviors.(379)

Appendix M: Tools used to Measure Activity Level in Osteoarthritis

Performance Based Measures

a. 40-Meter Fast-Paced Walk Test (40m FPWT)(381-383)

Purpose: Assess short-distance walking speed and functional mobility.

Description: Patient walks 4×10 meters at a fast, safe pace; total time recorded.

Psychometric Properties: Demonstrates excellent intra- and inter-rater reliability (intraclass correlation coefficient [ICC] >0.90), strong construct validity, and high responsiveness to clinical change in hip and knee OA. Included in the Osteoarthritis Research Society International (OARSI) core performance battery.

Clinical Utility: Simple to administer in most clinical settings; provides a sensitive measure of community ambulation capacity and treatment response.

b. Stair Climb Test (SCT)(381-384)

Purpose: Measure ability to ascend and descend stairs, reflecting higher-demand functional tasks.

Description: Patient climbs a standardized flight of stairs (typically 9–11 steps); ascent or total time recorded.

Psychometric Properties: Strong reliability and validity; responsiveness comparable to the 40m FPWT. Supported within the OARSI core performance set.

Clinical Utility: Highly relevant to daily activities and occupational demands; assists in evaluating functional limitations and progress following rehabilitation.

c. 30-Second Chair Stand Test (30s CST)(381-384)

Purpose: Evaluate lower-extremity strength and functional endurance.

Description: Number of sit-to-stand repetitions completed in 30 seconds using a standard chair.

Psychometric Properties: Good reliability across clinical environments; more modest construct validity and responsiveness relative to 40m FPWT and SCT. Part of the OARSI core set.

Clinical Utility: Quick, equipment-free assessment suitable for primary care, rehabilitation, and repeated monitoring of functional strength.

d. Timed Up and Go (TUG)(381-385)

Purpose: Assess global mobility, including transfers, gait, turning, and balance.

Description: Time required to rise from a chair, walk three meters, turn, return, and sit.

Psychometric Properties: Good reliability and discriminative validity; responsiveness is moderate and may show ceiling effects in higher-functioning individuals.

Clinical Utility: Useful for mobility and fall-risk screening; widely implemented in geriatric, Physical Medicine and Rehabilitation (PM&R), and physical therapy settings.

e. 6-Minute Walk Test (6MWT)(381-384)

Purpose: Measure walking endurance and submaximal aerobic capacity.

Description: Total distance walked in six minutes on a straight or looped course.

Psychometric Properties: Strong reliability and responsiveness in OA populations, particularly when evaluating rehabilitation or aerobic conditioning.

Clinical Utility: Appropriate when assessing sustained ambulation, community mobility, or exercise tolerance; requires adequate space and staff monitoring.

Patient-Reported Outcome Measures (PROMs)

a. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) (386-388)

Purpose: Assess pain, stiffness, and functional limitations specific to hip and knee OA.

Description: 24-item questionnaire with validated subscales for pain, stiffness, and physical function.

Psychometric Properties: Excellent reliability, strong construct validity, and high responsiveness with established MCID thresholds.

Clinical Utility: Widely used in clinical trials and routine practice; recommended as a core PROM for OA.

b. Lower Extremity Activity Scale (LEAS)(389)

Purpose: Capture daily activity levels related specifically to lower-extremity use.

Description: Ordinal scale assessing standing, walking, and ambulation patterns.

Psychometric Properties: Demonstrates good reliability and construct validity; fewer data available on responsiveness.

Clinical Utility: Useful as a supplemental measure when habitual activity patterns are important for clinical or functional assessment.

c. University of California Los Angeles (UCLA) Activity Rating Scale(389,390)

Purpose: Assess overall physical activity level, ranging from sedentary to high-impact participation.

Description: Single-item, 10-level ordinal activity scale.

Psychometric Properties: Acceptable reliability and validity in hip and knee OA; commonly used in arthroplasty and activity-level research.

Clinical Utility: Provides a rapid snapshot of habitual activity useful for clinical monitoring and shared decision-making.

d. Knee Injury and Osteoarthritis Outcome Score (KOOS)(386,391,392)

Purpose: Provide a comprehensive assessment of knee-related symptoms, function, sport/recreation, and QoL.

Description: Five-domain PROM extending the WOMAC structure; short forms (Knee Injury and Osteoarthritis Outcome Score for Joint Replacement [KOOS-JR]) available.

Psychometric Properties: Strong validity and responsiveness, especially in younger, active patients and peri-arthroplasty populations.

Clinical Utility: Useful when broader functional domains are relevant or when monitoring outcomes following surgical or high-intensity rehabilitation interventions.

e. Hip Disability and Osteoarthritis Outcome Score (HOOS)(393,394)

Purpose: Assess hip-specific pain, functional limitation, sport/recreation, and QoL.

Description: Modeled parallel to KOOS with short form (Hip Disability and Osteoarthritis Outcome Score, Joint Replacement [HOOS-JR]) alternatives.

Psychometric Properties: Well-validated in HOA and arthroplasty cohorts with strong reliability and responsiveness.

Clinical Utility: Appropriate when detailed hip-specific symptoms and activity assessment is required beyond WOMAC.

f. Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function(386,395)

Purpose: Evaluate general physical function across a wide range of musculoskeletal conditions.

Description: Computer adaptive test or short-form item sets derived from a large item bank.

Psychometric Properties: Strong reliability and validity in lower-extremity OA; captures functional limitations across global domains.

Clinical Utility: Useful when a generic, cross-condition functional measure is desired or when comparing function across different musculoskeletal diagnoses.

g. UCLA Activity Rating Scale(389)

Purpose: Assess overall physical activity level, ranging from sedentary to high-impact participation.

Description: Single-item, 10-level ordinal activity scale.

Psychometric Properties: Acceptable reliability and validity in hip and knee OA; commonly used in arthroplasty and activity-level research.

Clinical Utility: Provides a rapid snapshot of habitual activity useful for clinical monitoring and shared decision-making.

Appendix N: Abbreviation List

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