Osteogenesis imperfecta (OI) is a heritable disorder of bone that affects an estimated 20,000 individuals in the U.S. Oi is the result of different mutations affecting either the pro-alpha 1 or pro-alpha 2 polypeptide chains of type 1 collagen. Four clinical OI phenotypes have been defined, ranging from Type I disease which is of mild clinical severity, to Type II disease which is lethal, to Type III disease which is severe, and to Type IV disease which is of moderate severity. The Type I (mild) OI phenotype may include individuals considered to have familial idiopathic osteoporosis. Collagen abnormalities like Type I OI have een determined in our laboratories in subjects with mild adult osteoporosis of undetermined etiology. Although many therapies have been used in OI, none has been successful in strengthening bone or decreasing the fracture rate. Bisphosphanate drugs have been used successfully in treating post-menopausal osteoporosis. We have employed an effective bisphosphanate, Pamidronate (Ciba), administered intraveneously every three months, in the treatment of mild (Type I) OI. In this study, each subject serves as his own control. Study parameters include histomorphometric analysis of tetracycline-labeled bone biopsies obtained before and after two years of treatment. Data collection includes Core Lab analyses, diet history and CDMAS data management. Preliminary data analysis indicates that baseline bone turnover is low in subjects with Type I OI. Of the two subjects who have compeletd the two- year course of treatment, bone densitometry (DEXA) and bone histomorphometry results indicate bone mass has increased slightly in one subject and significantly in the second subject. Analysis of other subjects is pending. Administration of Pamidronate to children with more severe types of OI has demonstrated a positive effect on bone mass. The response of children and adults with different types of OI may vary. This data is important in view of the recent availability of potent bisphosphanates active by oral administration, and the intense interest in these agents on the part of the OI population seeking effective treatment.
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