Bone Quality in Hypoparathyroidism: Effects of PTH

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DESCRIPTION (provided by applicant): Hypoparathyroidism is one of the few remaining hormonal deficiency states for which replacement with the missing hormone has been unavailable. It is also a disorder for which very little is known about how chronic parathyroid hormone deprivation affects the skeleton and how parathyroid hormone can restore these abnormal skeletal features. Along with abnormal calcium homeostasis, namely hypocalcemia and hyperphosphatemia, parathyroid hormone deficiency leads to reduced skeletal turnover. Reduced skeletal turnover leads to overly mature, hypermineralized bone. The purpose of this study is to test the hypothesis that in hypoparathyroidism, the skeleton is abnormal in its densitometric, geometric and microarchitectural elements and that PTH will return these characteristics towards normal. In this way, we can understand better the properties of the skeleton in the state of PTH deprivation and in what specific ways, PTH restores the qualities of bone that contribute to bone strength. A secondary goal of this project is a therapeutic one. The use of parathyroid hormone should theoretically be the ideal approach to therapy. It replaces what is missing in the patient with hypoparathyroidism. This project will utilize the following technologies to evaluate the skeleton before and after parathyroid hormone in hypoparathyroidism: bone mass by DXA and QCT, bone turnover, bone geometry; mineralization density, classical static and dynamic histomorphometry, microCT analysis of bone biopsy specimens, and cellular elements of bone. By evaluating bone that is chronically deprived of PTH and then replaced with it, observations not heretofore been made will be possible and provide information on how and in what ways PTH is important to skeletal competence. As a young clinical investigator, I expect that this project will allow me to acquire critical new research skills in the assessment of metabolic bone disease, provide new understanding of this particular disorder, and by doing so, will propel me to the next level of my career.