title: Clinical approach to clarifying the mechanism of abnormal bone metabolism in McCune-Albright syndrome.
abstract: Recent advances in our knowledge of the abnormal bone metabolism associated with McCune-Albright syndrome (MAS) is briefly reviewed. Polyostotic fibrous bone dysplasia and hypophosphatemia are well-known characteristics of MAS. To clarify the mechanism of bone dysplasia, an approach that uses human cells isolated from MAS patients was important. It is now clear that normal skeletal stromal cells without mutation of the Gsalpha protein are necessary for the presence of bone dysplasia and that exaggerated production of interleukin-6 by fibrous bone cells with mutation of the Gsalpha protein is linked to the increased number of osteoclasts in bone tissues. The observation of increased bone resorption by the increased osteoclasts is one of the reasons for using bisphosphonates to treat the bone lesions of MAS. The key observation of the mechanism of hypophosphatemia in MAS was in a clinical report, which suggested that the presence of some humoral factors regulate phosphate metabolism. Recently, the humoral factor that causes hypophosphatemia in MAS was clarified to be fibroblast-growth factor 23 (FGF-23), although the possibility of some other humoral factors was not excluded. This is because a humoral factor inhibiting intestinal phosphate transport is present in culture medium obtained from the cells derived from fibrous bone dysplasia. The abnormal vitamin D mechanism in response to hypophosphatemia in MAS patients also proved recently to be caused by the increased circulating FGF-23 levels. The lines of evidence described suggest that FGF-23 and other factors may coexist, causing hyperphosphaturia and impaired intestinal absorption of phosphate, respectively.
authors.affiliation: Department of Pediatrics, Minoh City Hospital, 5-7-1 Kayano, Minoh 562-8562, Japan. takehisa_yamamoto@maple.city.minoh.lg.jp
authors.forename: Takehisa
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D001842:Bone and Bones / Q000378:metabolism*; D004164:Diphosphonates / Q000627:therapeutic use; D000089703:Fibroblast Growth Factor-23; D005359:Fibrous Dysplasia, Polyostotic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010010:Osteoclasts / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism
chemical_list: D004164:Diphosphonates; C000717427:FGF23 protein, human; D000089703:Fibroblast Growth Factor-23