Studies on Abnormal Bone From Patients With Polyostotic Fibrous Dysplasia and McCune Albright Syndrome - Full Text View

Purpose

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 juvenile dermatomyositis.

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.

Condition
Polyostotic Fibrous Dysplasia


Study Type:	Observational
Official Title:	Studies on Tissues From Patients With Fibrous Dysplasia of Bone/McCune-Albright Syndrome and Other Disorders of Calcified Tissues

Resource links provided by NLM:

Genetics Home Reference related topics: McCune-Albright syndrome geleophysic dysplasia mucopolysaccharidosis type IV

Genetic and Rare Diseases Information Center resources: Dermatomyositis Fibrous Dysplasia McCune-Albright Syndrome Juvenile Dermatomyositis Mucopolysaccharidosis Type IV

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):


Study Start Date:	December 1996
Estimated Study Completion Date:	December 2008

Detailed Description:

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.

Eligibility


Ages Eligible for Study:	Child, Adult, Senior
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001973

Locations


United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Institute of Dental and Craniofacial Research (NIDCR)

More Information


ClinicalTrials.gov Identifier:	NCT00001973 History of Changes
Obsolete Identifiers:	NCT00001607
Other Study ID Numbers:	970055 97-D-0055
Study First Received:	January 18, 2000
Last Updated:	September 26, 2015
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):


G Protein Mutation McCune-Albright Syndrome Fibrous Dysplasia Mutation Pathology	Immunohistochemistry PCR In Situ Hybridization Juvenile Dermatomyositis Calcinosis

Additional relevant MeSH terms:


Syndrome Hyperplasia Fibrous Dysplasia, Polyostotic Fibrous Dysplasia of Bone Disease	Pathologic Processes Osteochondrodysplasias Bone Diseases, Developmental Bone Diseases Musculoskeletal Diseases

ClinicalTrials.gov processed this record on September 30, 2016