Two major research projects will be undertaken: (1) a clinical study to elucidate the role of alterations of the various calcium and bone regulating hormones in the pathogenesis of diabetic osteopenia, and 2) a project to develop a radioimmunoassay for the isoenzyme of alkaline phosphatase derived from bone. The RIA will be used to assay serum samples from patients with the various forms of hypophosphatasia - a crippling inborn error of metabolism - to gain insight into the clinical and genetic variability of this disorder. Juvenile and adult diabetics will be studied longitudinally on the Clinical Research Center, Barnes Hospital so that changes in circulating parathyroid hormone, calcitonin, vitamin D metabolites, estrogens, etc. can be contrasted with studies of bone density and gastrointestinal calcium absorption. Differences in the degree of osteopenia, known to differ in various diabetic populations, should be reflected in dietary calcium absorption and circulating serum 1,25(OH)2D levels. Identification of hormonal differences between diabetics with and without osteopenia should provide clues to the pathogenesis of this frequent complication and suggest possibilities for corrective therapy. Normal fetal and neonatal bone will be extracted and purified for development of an RIA for normal bone AP isoenzyme. Routine methods will be used to develop the RIA once purified antigen is available. The RIA will be used to study the variability in clinical expression of this disorder, the variability in its genetic transmission, to identify """"""""carriers"""""""", and in prenatal diagnosis.
Showing the most recent 10 out of 497 publications
