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Fibrous dysplasia of bone
A rare, benign, primary bone dysplasia characterized by progressive replacement of normal bone and marrow with fibrous connective tissue in either one (monostotic) or multiple (polyostotic) bones. Clinical manifestations depend on the anatomic location of the replacement and may include bone pain, deformities, pathological fractures, and cranial nerve deficits.
ORPHA:249Classification level: Disorder
- Synonym(s): -
- Prevalence: Unknown
- Inheritance: Not applicable
- Age of onset: Adolescent, Adult, Childhood
- ICD-10: Q78.1
- OMIM: -
- UMLS: C0016063
- MeSH: D005357
- GARD: 6444
- MedDRA: 10016664
The prevalence is unknown and is difficult to estimate due to the frequent asymptomatic lesions.
FD can involve the craniofacial, axial, and/or appendicular skeleton separately or simultaneously, and ranges from isolated asymptomatic monostotic lesions to severely incapacitating polyostotic lesions leading to pain, fracture, deformity or loss of vision and hearing. The monostotic form represents approximately 70% of cases, may present with pain or a pathologic fracture, and is usually diagnosed between 10 to 30 years of age. The polyostotic form represents 20-30% of cases with the majority of patients becoming symptomatic before 10 years of age. The most common sites of involvement include the femur, tibia, skull and facial bones, pelvis, rib, humerus, radius and ulna, lumbar spine, clavicle, and cervical spine. Lesions may be unilateral or, less commonly, bilateral. Initial symptoms are usually pain in the involved limb(s), associated with a limp if the lower extremity is involved, and spontaneous fracture. Weakened structural integrity frequently leads to significant bowing and leg-length discrepancies in patients with limb involvement. Sphenoidal bone involvement is variably associated with cranial nerve deficits, essentially loss of vison (affecting less than 10% of individuals with optic nerve compression). Many patients with polyostotic forms also present with renal phosphate wasting, which accounts for an increased risk of fracture. At the extreme end of the spectrum, a small proportion of patients also have endocrine manifestations, the most common being a peripheral precocious puberty. Hyperthyroidism and growth hormone hypersecretion are also quite frequently observed, while Cushing syndrome is exceptional. These patients also have café-au-lait cutaneous spots. These endocrine or cutaneous features represent the McCune-Albright syndrome. Pancreatic intraductal papillary mucinous neoplasms have been described in patients with extended forms.
Activating somatic mutations in the GNAS gene (20q13.32), which encodes the alpha-subunit of the Gs protein receptor (Gsalpha) in target cells, is responsible for bone cell alterations as well as for the involvement of other cells/tissues bearing the same molecular defect (melanocytes, endocrine cells).
Imaging and, when necessary, histology are the cornerstones of diagnosis. The pathognomonic radiological picture includes radiolucency and a ''ground glass'' appearance (with no visible trabecular pattern in affected areas), variable presence of endosteal scalloping of the inner cortex (but with a smooth nonreactive periosteal surface), curvature of the femoral neck and proximal shaft (often causing a coxa vara deformity of the knee), and shepherd's crook deformity.
Differential diagnoses includes osteofibrous dysplasia, osteochondroma, exostosis, osteosarcoma, chondrosarcoma, osteofibroma, skull meningioma, osteoma
Mutations affect only somatic cells and are therefore not hereditary, thus genetic counseling may provide reassurance but is not strictly necessary.
Management and treatment
The conventional therapeutic approach is essentially symptomatic (analgesics) and orthopedic (prevention and treatment of bone complications). Treatment is typically with intravenous pamidronate, which rapidly relieves bone pain in most patients, and progressively increases bone mineralization in osteolytic areas in about half of patients. In contrast, placebo controlled randomized trials have shown that oral bisphosphonates are no more efficacious than placebo to reduce bone pain. Tubular phosphate wasting is common and should be treated with phosphate supplementation and calcitriol.
Prognosis is generally good in patients with the monostotic form. Polyostotic patients need to be monitored more closely, but as disease has a tendency to stabilize after adolescence, outcomes are often good in adults.
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