Fibrous Dysplasia of Bone

Fibrous dysplasia of bone is a benign skeletal disorder in which normal bone is replaced by fibro osseous tissue because of a post-zygotic activating GNAS variant. It affects one bone (monostotic, 70 to 80%) or several (polyostotic).

Lesions appear in childhood and expand until adolescence. Common sites are the proximal femur, craniofacial bones, ribs and tibia. Polyostotic disease with skin macules and endocrine hyperfunction defines McCune-Albright syndrome.

Fibrous dysplasia accounts for about 5 to 7% of benign bone tumours. Malignant transformation (osteosarcoma) is rare, under 1%.

Pathophysiology.

Mosaic activating GNAS variants cause constitutive Gs alpha signalling in osteoprogenitor cells, with abnormal differentiation, poor mineralisation and woven bone. Raised FGF23 from dysplastic bone causes renal phosphate wasting in some patients.

• Bone pain, deformity (shepherd's crook deformity of the femur), pathological fracture, facial asymmetry and leg length difference.
• Craniofacial disease: proptosis, hearing loss, visual loss from optic canal narrowing (uncommon).
• Skin café-au-lait macules and endocrine features if McCune-Albright syndrome is present.

Red flags.

• Visual loss or hearing loss.
• Rapidly growing painful lesion (sarcoma), pathological fracture, or severe hypophosphataemia.

• Radiographs: ground glass lesion with sclerotic margins, bone expansion and cortical thinning. CT for skull base and complex lesions; MRI for soft tissue assessment.
• Technetium bone scan to map disease extent.
• Calcium, phosphate, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D and FGF23. Thyroid function, IGF-1, cortisol tests and puberty assessment in polyostotic disease or skin macules.
• Biopsy if the diagnosis is uncertain. GNAS testing of lesion tissue.

Differential diagnosis.

• Paget disease, osteofibrous dysplasia, ossifying fibroma and non-ossifying fibroma.
• Giant cell tumour, brown tumour of hyperparathyroidism and bone cysts.
• Osteosarcoma, metastasis and Langerhans cell histiocytosis.

• Asymptomatic lesions: observation with clinical review and imaging.
• Pain: analgesia and bisphosphonate (pamidronate 0.5 to 1 mg/kg infusion every 3 to 6 months, or zoledronic acid or alendronate 70 mg weekly in adults), which relieves pain but has uncertain effect on lesion size or fracture. Denosumab can cause rebound hypercalcaemia on stopping and is used under specialist care.
• Fractures and deformity: surgery with intramedullary fixation (avoid curettage and bone grafting alone, which fail).
• Craniofacial: monitor optic nerve and hearing, and operate for functional compromise only; do not decompress prophylactically.
• Hypophosphataemia: elemental phosphorus 1 to 3 g daily in 3 to 5 divided doses with calcitriol 0.5 to 1.5 micrograms daily (children 20 to 40 mg/kg and 20 to 30 nanograms/kg daily). Calcium and vitamin D replacement.
• Radiotherapy is contraindicated because of sarcoma risk. Evaluate and treat endocrine disease (precocious puberty, hyperthyroidism, growth hormone excess).

Special groups. Pregnancy: lesions may enlarge with raised oestrogen; monitor symptoms. Children: orthopaedic and endocrine team follow up through growth.

Monitoring. Symptoms, imaging every 1 to 2 years while lesions are active, phosphate and alkaline phosphatase yearly, and thyroid function and growth hormone screening in polyostotic disease.

Referral and escalation. Endocrinology and orthopaedics; ophthalmology and ENT for craniofacial disease; urgent review for visual loss or suspected sarcoma.