Bone Abstracts

Fibrous dysplasia of bone (FD) is a rare bone disease affecting one or several bones, due to a somatic mutation of GNAS responsible for abnormal differentiation of the osteoblastic cell lineage. The bone lesions may be associated with bone pain, fracture, deformity and neurologic compression. McCune-Albright syndrome is an association of FD, endocrine complications - mainly peripheral precocious puberty - and café-au-lait cutaneous spots.

The mutated cells produce a fibrous tissue within the trabecular compartment, but also an excess of RANKL and IL-6 leading to increased osteoclastogenesis and bone resorption. In polyostotic forms an excess in FGF23 can lead to renal phosphate wasting, which causes bone pain and fracture by osteomalacia. Two thirds of the patients are affected by a monostotic form. The diagnosis may include simple radiographs, computerized tomography (CT), magnetic resonance imaging (MRI) and histopathology combined with molecular analysis of GNAS. A bone scan has to be performed at least once to establish a map of all lesions. Specific forms need special attention because of the risk of complications. At the femur, the observation of a large lytic lesion may justify a preventive osteosynthesis. Cranio-facial lesions must be monitored for the risk of optic nerve compression, but also for growth hormone excess. The differential diagnosis with the meningioma is also of paramount importance at this site. The treatment of bone pain has relied on the use of bisphosphonates (mainly IV), which are efficacious in 80% of patients. More recently, denosumab has been entered into small clinical studies, with conflicting results so far. Tocilizumab - a monoclonal antibody to the receptor of IL-6 - is on trial to treat FD. Drugs targeting some specific mechanisms of FD bone pain may be developed in the future.