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.