BONE PROPERTIES IN HYPOPARATHYROIDISM: EFFECTS OF PTH

描述(申请人提供)：虽然许多关于甲状旁腺功能亢进症(一种甲状旁腺激素(PTH)过多的疾病)的骨骼特性是已知的，但对于甲状旁腺功能减退症(一种甲状旁腺激素缺乏的疾病)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骨骼的代谢、密度、几何、生物力学和微结构特征异常的假说。我们还将检验骨骼依赖于甲状旁腺激素以获得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，人类甲状旁腺功能低下的骨骼将得到彻底的表征。每个患者作为自己的对照，我们将确定甲状旁腺激素的应用如何、在多大程度上以及以什么方式恢复甲状旁腺功能低下的骨骼动力学和结构。通过这种方式，我们将确定受PTH影响或依赖于PTH的骨架的结构和动态元素。可利用的方法包括双能X线骨密度计、定量中心和外周计算机断层扫描、几何和大小量化、标准和显微CT方法的组织形态计量学、有限元分析、生化骨标记、定量背散射电子成像和傅立叶变换红外光谱。本研究将使我们对甲状旁腺激素的骨骼效应的认识扩大到其不足的范围，从而完善我们多年研究甲状旁腺功能亢进症甲状旁腺激素过表达对骨骼作用的认识。这项研究还可能为甲状旁腺激素在用于治疗骨质疏松症时帮助恢复骨骼的方法提供洞察力。

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.