This study will investigate how a gene mutation (change in DNA) causes the abnormal bone in
fibrous dysplasia-a condition in which areas of normal bone are replaced with a fibrous
growth similar to a scar. The bone abnormalities in fibrous dysplasia can occur in a single
bone (monostotic fibrous dysplasia), multiple bones (polyostotic fibrous dysplasia), or in
McCune Albright syndrome, in which there are associated glandular abnormalities. This study
will also examine calcinosis samples that have been surgically removed from patients with
Patients who are scheduled to have orthopedic surgery for treatment of polyostotic fibrous
dysplasia may participate in this study. A small sample of bone tissue removed during
surgery will be given to investigators in this study for research tests. DNA will be
extracted from the tissue and tested for the mutation. Investigators will attempt to grow
cells from the sample in the laboratory to evaluate them for their ability to grow and make
proteins that normal bone cells make. These tests are designed to help scientists understand
how the mutation leads to abnormal bone formation and provide information that might lead to
better treatments for fibrous dysplasia. Patients with juvenile Dermatomyositis who have a
calcinosis sample surgically removed are also eligible for participation. The removed
tissues will be examined for their composition and microscopic appearance, to better
understand the pathogenesis of dystrophic calcification in this disease.
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.
- INCLUSION CRITERIA:
All patients who are scheduled to have orthopedic surgery for treatment of polyostotic
fibrous dysplasia (PFD).
Tissue will only be obtained from those patients in whom the procedure is clinically
indicated for standard reasons such as treatment of or prevention of fractures, or
disfigurement resulting from abnormal growth of facial and/ or skull bones.
The diagnosis of PFD will have been established by standard radiologic criteria and in
patients with McCune Albright syndrome (MAS), also by the characteristic skin and
endocrine manifestations associated with that form of the disease.
Patients meeting criteria for juvenile dermatomyositis who undergo surgical removal of
calcinosis are eligible. The tissue from surgery would be used in the research study.