Endocrine Society 2019: pharmacologic management of postmenopausal osteoporosis

Who it applies to

Postmenopausal women being considered for or already on pharmacologic therapy for osteoporosis or high fracture risk.

Key recommendations

• Postmenopausal women at high risk of fracture should be offered pharmacologic therapy rather than no treatment.
• Oral bisphosphonates (alendronate or risedronate) are recommended as initial therapy for most postmenopausal women with osteoporosis given their efficacy, safety record, and low cost.
• For women at very high fracture risk (e.g., multiple vertebral fractures, very low bone density, or recent fracture), anabolic agents such as teriparatide or abaloparatide, or denosumab, should be considered as initial therapy rather than oral bisphosphonates.
• Intravenous zoledronic acid is recommended for women who cannot tolerate or adhere to oral bisphosphonates, or who have upper gastrointestinal contraindications.
• Denosumab is recommended for women at high fracture risk, including those with renal impairment where bisphosphonates may be less suitable, with attention to the risk of rebound vertebral fractures if discontinued without follow-up therapy.
• After stopping denosumab, transition to a bisphosphonate is advised to mitigate the rebound increase in bone turnover and vertebral fracture risk.
• Following a course of anabolic therapy (teriparatide or abaloparatide), an antiresorptive agent (bisphosphonate or denosumab) should be started to maintain or augment bone density gains.
• A bisphosphonate drug holiday may be considered after several years of therapy in women who are no longer at high risk, with periodic reassessment of fracture risk during the holiday.
• Raloxifene or other selective estrogen receptor modulators may be considered for women at risk of vertebral fracture when bisphosphonates are not appropriate, though they are less effective at reducing nonvertebral and hip fracture risk.
• Calcium and vitamin D intake should be optimized, through diet or supplementation, in all women receiving osteoporosis pharmacotherapy.
• Combination therapy with two osteoporosis drugs simultaneously is generally not recommended outside specific circumstances given limited evidence of added benefit.

What is new in this edition

• Expanded guidance on sequencing therapies, particularly the use of antiresorptive therapy after anabolic agents and after denosumab discontinuation
• Greater emphasis on identifying very-high-risk patients as a distinct category warranting anabolic-first treatment strategies

Practice points for students

• Never stop denosumab without transitioning to a bisphosphonate because of rebound vertebral fracture risk.
• Anabolic agents should generally precede antiresorptive therapy, not follow it, to maximize bone density benefit.
• Oral bisphosphonates remain first-line for average-risk postmenopausal osteoporosis due to cost and long safety track record.
• Drug holidays apply mainly to bisphosphonates, not to denosumab or anabolic agents.
• Renal impairment is a key factor pushing therapy choice away from bisphosphonates toward denosumab.

Condition

Other guidelines on this topic

• The 2024 UK clinical guideline for the prevention and treatment of osteoporosisNOGG2025Full text
• Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults: A Living Clinical Guideline From the American College of PhysiciansACP2023Summary
• European guidance for the diagnosis and management of osteoporosis in postmenopausal womenIOF/ESCEO2019Summary
• Guidelines for the management of osteoporosis and fragility fracturesSIMFER/SIOMMMS/SIR/SIOT2019Full text

Independent educational summary written by the WhiteCoat Pro editorial team with AI assistance and checked by a second AI model. It does not reproduce the guideline text, tables or figures, and it is not affiliated with or endorsed by Endocrine Society. It is not medical advice: always read the original guideline before applying it to patients.