Fibrous dysplasia of bone

Fibrous dysplasia of bone (FD) is a rare skeletal disorder in which normal bone and marrow are replaced by fibrous tissue and abnormally developed (dysplastic) bone. It is caused by somatic (postzygotic) activating mutations in the GNAS gene, which encodes the alpha subunit of the stimulatory G protein (Gsα). Because the mutation occurs after conception during embryonic development, it is not inherited from a parent but arises sporadically, resulting in a mosaic pattern of affected tissues. The disease can involve a single bone (monostotic fibrous dysplasia, the most common form, accounting for approximately 70-80% of cases) or multiple bones (polyostotic fibrous dysplasia). When polyostotic fibrous dysplasia occurs together with café-au-lait skin pigmentation and endocrine hyperfunction (such as precocious puberty), the condition is known as McCune-Albright syndrome. Fibrous dysplasia primarily affects the skeletal system, with the most commonly involved bones being the femur, tibia, ribs, skull, and facial bones. Key symptoms include bone pain, skeletal deformities (such as leg bowing or facial asymmetry), pathological fractures, and limb-length discrepancy. Craniofacial involvement can lead to facial asymmetry, vision or hearing impairment due to nerve compression, and dental abnormalities. The severity of the disease varies widely, ranging from an incidental finding on X-ray to severely disabling skeletal disease. Symptoms typically present in childhood and may progress during growth, often stabilizing after skeletal maturity, although complications can continue into adulthood. There is currently no cure for fibrous dysplasia. Treatment is primarily supportive and symptom-directed. Bisphosphonates (such as pamidronate or zoledronic acid) may be used to manage bone pain, although their effect on preventing fractures or disease progression remains uncertain. Surgical intervention may be necessary for pathological fractures, significant skeletal deformities, or nerve compression, particularly in the craniofacial region. Orthopedic stabilization with intramedullary rods is sometimes employed for weight-bearing bones prone to fracture. Regular monitoring by a multidisciplinary team including orthopedists, endocrinologists, and craniofacial specialists is recommended, especially in polyostotic and McCune-Albright syndrome cases.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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