Osteopetrosis

Forms of osteopetrosis and their manifestations

Autosomal recessive (lethal) type manifests in infancy. Obliteration of the medullary cavity causes severe anemia, thrombocytopenia, and frequent infections. Patients present with hepatosplenomegaly and hydrocephalus. Due to the narrowing of the skull foramina, cranial nerves are compressed, leading to blindness and deafness.

Intermediate recessive form has a milder course, accompanied by short stature, anemia, and fractures.

Autosomal dominant type (Albers-Schönberg disease) is considered benign. It is often asymptomatic and discovered incidentally. However, facial nerve palsy, deafness, anemia, and a high risk of mandibular osteomyelitis following tooth extraction are possible. According to the Andersen and Bollerslev classification, it is divided into:

• Type I: fractures are not characteristic.
• Type II: frequent fractures, transverse bands in the metaphyses, and elevated acid phosphatase levels.

Radiological and MRI findings in osteopetrosis

On radiographs, bones appear extremely dense, with a complete loss of normal cortico-medullary differentiation.

Main radiological signs:

• Impaired tubulation (under-tubulation): metaphyseal zones are widened and flask-shaped. This feature is especially noticeable in the distal femur and proximal humerus.
• «Bone within a bone» sign (bone within a bone): the contours of the original bone are visible inside the new enlarged bone (typical for intermediate and dominant forms).
• «Sandwich» vertebrae (sandwich appearance): marked sclerosis of the superior and inferior endplates against the background of a less dense central part of the vertebral body.
• Skull involvement: sclerosis predominantly affects the base, while the mastoid air cells and paranasal sinuses are underdeveloped.

Magnetic resonance imaging (MRI) is used mainly to monitor treatment efficacy in severe forms after bone marrow transplantation. Successful graft engraftment is confirmed by the expansion of the medullary cavity.

Hyperphosphatasia (Juvenile Paget's disease)

This is a rare genetic pathology associated with osteoprotegerin deficiency (TNFRSF11B gene mutation). It is characterized by a sharply accelerated bone metabolism (bone turnover): immature woven bone fails to transform into normal lamellar bone. Laboratory tests reveal a significant increase in alkaline phosphatase levels.

Clinically in children, fever, pain, bowing of the long bones, short stature, and premature tooth loss (due to dentin resorption) are observed.

Radiological signs:

• Decreased bone density, coarse and disorganized trabecular pattern.
• Skull: thickening of the vault, widening of the diploë, basilar invagination.
• Long bones: widening of the diaphyses, bowing (leading to coxa vara and protrusio acetabuli).
• Spine: platyspondyly (biconcave vertebrae).

Radionuclide imaging shows the «super scan» sign (super scan) — diffuse tracer uptake in the skeleton without visualization of the kidneys. Unlike classical Paget's disease, hyperphosphatasia affects the entire skeleton and debuts as early as 2 years of age.

Effect of hypervitaminoses and fluorosis on the skeleton

Vitamin D intoxication (occurring during treatment for cancer, psoriasis, sarcoidosis) causes hypercalcemia. On radiographs, this manifests as metastatic calcification of ligaments, tendons, arteries, and fascia, resembling periostitis and causing sclerosis of the adjacent bone.

Hypervitaminosis A (during retinoid therapy) leads to the formation of large exostoses in the cervical spine and mild enthesopathy. In children, cup-shaped widening of the metaphyses, diaphyseal periostitis of the ulnae and metatarsal bones, and widening of the cranial sutures are observed.

Fluorosis develops with chronic excess fluoride. The main radiological signs are marked osteosclerosis of the axial skeleton, ligamentous ossification, and massive spinal osteophytes, which can cause compressive myelopathy.

Endocrine osteopathies

The skeleton responds sensitively to hormonal imbalance:

• Cushing's disease and syndrome: Excess glucocorticoids lead to osteoporosis of the axial skeleton. Low-energy fractures with excessive callus formation, as well as bone infarcts and avascular necrosis, are characteristic.
• Thyroid pathology: In children, hypothyroidism (cretinism) causes delayed skeletal maturation, epiphyseal fragmentation, «shoe»-shaped vertebrae, and the appearance of Wormian bones (Wormian bones) in the cranial sutures. In autoimmune diseases, thyroid acropachy may develop: tissue edema, digital clubbing («drumstick»ing), and periostitis of the tubular bones of the hand.
• Acromegaly: A pituitary tumor causes cartilage hypertrophy. In the early stages, this looks like widening of the joint spaces (especially in the metacarpophalangeal joints). Over time, the loose cartilage develops cracks, leading to early osteoarthritis and generalized osteoporosis.

Briefly: answers to topical questions

What else to study on this topic

• Pathogenesis of osteoclast dysfunction in osteopetrosis
• Andersen and Bollerslev classification in detail
• Differential diagnosis of sclerotic bone lesions
• Mechanisms of metastatic calcification in vitamin D intoxication
• Effect of glucocorticoids on bone remodeling in Cushing's syndrome

Other topics in the "Musculoskeletal System" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.