Studies on Tissues From Patients With Fibrous Dysplasia of Bone/McCune-Albright Syndrome and Other Disorders of Calcified Tissues

Polyostotic fibrous dysplasia (PFD) is a sporadic disorder in which multiple sites of bone are replaced by abnormal fibrous tissue. PFD may occur alone or as part of the McCune Albright syndrome (MAS). We have previously identified a somatic activating mutation in the gene encoding the alpha-subunit of Gs, the G protein which mediates the action of hormones that work by increasing intracellular levels of cyclic adenosine monophosphate (cAMP), in affected tissues from patients with PFD and MAS. The objectives of this study are to determine how activating mutations of the Gs alpha-subunit lead to the changes of PFD, and to determine if interventions that block the biochemical effects of the activating mutation in in vitro and in vivo animal model systems could prevent some of the cellular changes characteristic of PFD. To carry out these studies, we plan to obtain pathologic bone tissue from patients with either isolated PFD or PFD in the context of MAS. In one phase of the study, archival pathology specimens of affected bone will be retrospectively analyzed using a variety of immunohistochemical techniques. In the second phase of the study, specimens of affected bone will be obtained prospectively from patients undergoing clinically indicated orthopedic procedures. Specimens will be placed in primary culture, cultured cells will be analyzed for the Gs alpha-subunit activating mutation, and the mutant-bearing cells will be studied by a variety of cell biologic and pharmacologic techniques.