BONE PROPERTIES IN HYPOPARATHYROIDISM: EFFECTS OF PTH

描述（由申请人提供）：尽管关于原发性甲状旁腺功能亢进（一种甲状旁腺激素（PTH）过量的疾病）的骨特性已知很多信息，但关于甲状旁腺功能减退（一种缺乏PTH的疾病）的骨骼几乎一无所知。本研究的目的是验证甲状旁腺功能减退症患者的骨骼在代谢、密度、几何、生物力学和微结构特征方面异常的假设。我们还将测试骨骼依赖于PTH的正常结构和功能的假设。使用非侵入性的方法以及直接分析骨本身，人类甲状旁腺功能减退的骨骼将被彻底表征。每个病人作为他/她自己的控制，我们将确定如何，在何种程度上，以及以何种方式管理PTH恢复骨骼动力学和结构的甲状旁腺功能减退的骨骼。通过这种方式，我们将确定那些结构和动态元素的影响或依赖于PTH的骨骼。使用的方法包括双能X线吸收测定法、定量中心和外周计算机断层扫描、几何和尺寸定量、通过标准和microCT方法进行的组织形态测定、有限元分析、生化骨标记物、定量背散射电子成像和傅立叶变换红外光谱。本研究项目将扩展我们对PTH对骨骼影响的认识，使其在缺乏的范围内，从而完成我们多年来研究原发性甲状旁腺功能亢进症中PTH过表达所获得的PTH对骨骼作用的理解。这项调查也可能提供洞察PTH有助于恢复骨骼的手段，当它被用来治疗骨质疏松症。

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.