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激素缺乏症之一，无法用缺失的激素替代。它也是一种疾病，其中很少有人知道慢性甲状旁腺激素缺乏如何影响骨骼，以及甲状旁腺激素如何恢复这些异常的骨骼特征。沿着钙稳态异常，即低钙血症和高磷血症，甲状旁腺激素缺乏导致骨骼周转减少。减少骨骼周转导致过度成熟，高矿化骨。本研究的目的是检验假设，在甲状旁腺功能减退症，骨骼是异常的，其密度，几何和微结构元素，PTH将返回这些特征向正常。通过这种方式，我们可以更好地了解PTH剥夺状态下骨骼的特性，以及PTH以何种特定方式恢复有助于骨骼强度的骨骼质量。这个项目的第二个目标是治疗。使用甲状旁腺激素理论上应该是理想的治疗方法。它取代了病人甲状旁腺功能减退的部分。本项目将利用以下技术评价甲状旁腺功能减退症患者甲状旁腺激素治疗前后的骨骼：DXA和QCT骨量、骨转换、骨几何形状;矿化密度、经典静态和动态组织形态计量学、骨活检标本的microCT分析和骨细胞成分。通过评估长期缺乏PTH然后用其替代的骨，将有可能进行迄今为止尚未进行的观察，并提供关于PTH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者，我希望这个项目能让我在代谢性骨病的评估中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，将推动我进入职业生涯的下一个阶段。

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.