Bone Quality in Hypoparathyroidism: Effects of PTH

描述(由申请人提供)： 甲状旁腺功能减退症是为数不多的荷尔蒙缺乏症之一，无法用缺失的荷尔蒙来替代。这也是一种疾病，人们对慢性甲状旁腺激素剥夺如何影响骨骼以及甲状旁腺激素如何恢复这些异常的骨骼特征知之甚少。伴随着钙稳态的异常，即低钙血症和高磷血症，甲状旁腺激素缺乏会导致骨骼转换率降低。骨骼周转减少会导致过度成熟、过度矿化的骨骼。本研究的目的是验证甲状旁腺功能减退症患者骨骼的密度、几何和微结构元素异常以及甲状旁腺激素会使这些特征恢复正常的假说。通过这种方式，我们可以更好地了解甲状旁腺素剥夺状态下骨骼的特性，以及甲状旁腺素通过哪些具体方式恢复了有助于骨强度的骨质量。这个项目的次要目标是治疗目标。从理论上讲，甲状旁腺激素的使用应该是理想的治疗方法。它取代了甲状旁腺功能减退症患者所缺失的东西。该项目将利用以下技术评估甲状旁腺激素减退治疗前后的骨骼：DXA和QCT的骨量、骨转换、骨几何形状；矿化密度、经典的静态和动态组织形态计量学、骨活检标本的MicroCT分析，以及骨细胞元素。通过评估长期缺乏甲状旁腺素的骨骼，然后用甲状旁腺素替代，将有可能进行迄今尚未进行的观察，并提供关于甲状旁腺素如何以及以何种方式对骨骼能力重要的信息。作为一名年轻的临床研究人员，我希望这个项目将使我在评估代谢性骨骼疾病方面获得关键的新研究技能，提供对这种特殊疾病的新理解，并通过这样做，将我的职业生涯推向新的水平。

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.