Fibrous Dysplasia

Definition

Etiology / Pathogenesis

• Replace arginine with either cysteine or histidine
• Selectively inhibit GTPase activity, leading to constitutive activation of Gsα
• Raise intracellular cAMP levels, which promote cellular proliferation and disrupt osteoblast differentiation (via the Wnt pathway and others)

• Bone - autonomous PTH-receptor function
• Skin - melanocyte-stimulating hormone receptor (cafe-au-lait spots)
• Ovaries - FSH receptor (precocious puberty)
• Thyroid / pituitary - thyroid and growth hormone receptors

Classification

1st Classification (Standard)

2nd Classification (Stewart)

• Monostotic - single bone
• Monomelic - one extremity (rare)
• Polyostotic - many bones
• Albright's syndrome

Other

• Mazabraud syndrome - polyostotic FD + soft tissue myxomas (in the same anatomic region, myxomas appear in adulthood)
• Subclinical FD - lesion discovered incidentally on radiograph without any symptoms

Clinical Features

Monostotic FD

• Age/sex: Children under 10 years; both sexes equally
• Sites: Ribs, femur, tibia, maxilla, mandible, calvarium (most common sites)
• Symptoms: Painless swelling is the most common complaint; may cause pain and pathologic fracture
• Course: Often stops enlarging at growth plate closure; frequently asymptomatic

Polyostotic FD (Jaffe's type)

• Sex predilection: Female:male = 3:1
• Manifests slightly earlier than monostotic; may continue into adulthood
• Limb girdle involvement causes deformities and fractures
• Craniofacial involvement common
• 25% of cases are not diagnosed until after age 30 despite lesions developing during skeletal growth

McCune-Albright Syndrome

• Severely deformed bones, usually symptomatic before age 10
• Skin lesions often confined to one extremity
• Associated endocrine dysfunction: precocious puberty, hyperthyroidism, acromegaly, Cushing's syndrome

Morphology / Histopathology

• Intramedullary lytic lesions - may expand with bowing and cortical thinning
• Periosteal reaction is absent (key distinguishing feature)
• Lesional tissue is tan-white and gritty

• Curvilinear/irregular trabeculae of woven bone in a cellular fibrous stroma
• No osteoblastic rimming (absence of osteoblast rim around trabeculae is the key histological feature)
• Trabecular shapes resemble "Chinese letters" or curved alphabetic characters
• Moderately cellular fibroblastic proliferation
• Cystic degeneration, hemorrhage, and foamy macrophages also commonly present

Radiology

• "Ground-glass" appearance on plain X-ray - the most characteristic finding (due to mineralized woven bone spicules, not fibrous tissue)
• "Long lesion in a long bone" with symmetric cortical thinning and expansion
• Some lesions are entirely radiolucent; others radiodense
• In weight-bearing bones, deformity from multiple fractures is common
• FD producing fibroblast growth factor 23 (FGF-23) can cause secondary osteomalacia
• Rheumatology 2-Volume Set, p. 4006-4031

Complications

• Pathologic fracture (most common, especially in weight-bearing bones)
• Deformity - "shepherd's crook" deformity of the proximal femur in polyostotic disease
• Osteomalacia - via FGF-23 overproduction
• Malignant transformation - rare; sarcomatous transformation usually occurs in polyostotic disease; an important long-term complication to monitor - Robbins, Cotran & Kumar, p. 1399

Treatment

• Asymptomatic / monostotic: Observation; many small lesions are managed conservatively
• Symptomatic: Curettage (recurrence is common)
• Bone grafting may be required for lesions with pathologic fracture
• Bisphosphonates - reduce severity of bone pain in polyostotic disease
• Extensive skeletal involvement: Multi-modal approach - pain management, surgery, and bone strengthening
• Rheumatology 2-Volume Set, p. 4036-4038

Recent evidence (2025): A review published in Therapeutic Advances in Endocrinology and Metabolism (PMID 40538772) and a state-of-the-art review in Orphanet J Rare Dis (PMID 40781626) cover updated medical management strategies including investigational agents targeting the GNAS/cAMP pathway. These may update the classic bisphosphonate-only medical approach described in older textbooks.

Key Summary Table