BONE PROPERTIES IN HYPOPARATHYROIDISM: EFFECTS OF PTH

描述（由申请人提供）：尽管我们对原发性甲状旁腺功能亢进（一种甲状旁腺激素（PTH）过多的疾病）患者的骨骼特性了解很多，但对甲状旁腺功能低下（一种PTH缺失的疾病）患者的骨骼特性几乎一无所知。本研究项目的目的是验证甲状旁腺功能低下患者的骨骼在代谢、密度、几何、生物力学和微结构特征上的异常假设。我们还将测试骨骼依赖于甲状旁腺激素的正常结构和功能的假设。使用非侵入性方法以及对骨骼本身的直接分析，人类甲状旁腺下骨将被彻底表征。每个患者作为他/她自己的对照，我们将确定PTH的管理如何，在多大程度上和以何种方式恢复骨骼动力学和结构到甲状旁腺下骨骼。通过这种方式，我们将识别那些受甲状旁腺激素影响或依赖于甲状旁腺激素的骨骼结构和动态元素。使用的方法包括双能x射线吸收仪、定量中央和周围计算机断层扫描、几何和尺寸量化、标准和微ct方法的组织形态测量、有限元分析、生化骨标记、定量后向散射电子成像和傅里叶变换红外光谱。本研究项目将把我们对甲状旁腺激素对骨骼影响的认识扩展到其缺乏范围，从而完成我们多年来对原发性甲状旁腺功能亢进中甲状旁腺激素过表达的研究所获得的对甲状旁腺激素对骨骼作用的理解。这项研究也可能为PTH用于治疗骨质疏松症时帮助恢复骨骼的方法提供见解。

DESCRIPTION (provided by applicant): Whereas much information is known about the properties of bone in primary hyperparathyroidism, a disorder of parathyroid hormone (PTH) excess, virtually nothing is known about the skeleton in hypoparathyroidism, a disorder in which PTH is absent. The purpose of this research project is to test the hypothesis that the skeleton in hypoparathyroidism is abnormal in its metabolic, densitometric, geometric, biomechanical and microarchitectural features. We will also test the hypothesis that the skeleton is dependent upon PTH for normal structure and function. Using non-invasive approaches as well as direct analysis of bone itself, the human hypoparathyroid skeleton will be thoroughly characterized. With each patient serving as his/her own control, we will determine how, to what extent, and in what ways the administration of PTH restores skeletal dynamics and structure to the hypoparathyroid skeleton. In this way, we will identify those structural and dynamic elements of the skeleton that are influenced by or dependent upon PTH. Methods to be utilized include dual energy X-ray absorptiometry, quantitative central and peripheral computed tomography, geometry and size quantification, histomorphometry by standard and microCT methods, finite element analysis, biochemical bone markers, quantitative back scattered electron imaging, and Fourier Transform Infrared Spectroscopy. This research project will extend our knowledge of the skeletal effects of PTH to its deficient range and thus complete our understanding of PTH action on bone gained by our many years of studying PTH overexpression in primary hyperparathyroidism. This investigation may also provide insight into the means by which PTH helps to restore the skeleton when it is used to treat osteoporosis.