ROLE OF BONE IN ABSORPTIVE HYPERCALCIURIA

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。吸收性高钙尿症（AH）是肾结石的主要病因之一，其特征是肠道钙的过度吸收。虽然在这种情况下骨丢失是意料之外的，但根据几项骨密度研究，它在严重疾病中特别常见。一些小型研究通过组织形态计量学分析对高钙尿石症患者的髂嵴骨活检进行了研究，但未对受试者进行充分描述。因此，目前尚不清楚重度AH中的骨丢失是由于低形成还是过度骨吸收，以及骨是否有助于高钙尿状态。 本项目的目的是更好地阐明重度AH中骨丢失和高钙尿症的病理生理机制，以制定更合理的治疗方法。假设为：1）重度AH受试者中骨丢失的主要原因是骨吸收正常或略微增加的情况下骨形成减少，2）重度AH中的高钙尿症主要是由肠钙吸收过度引起的，但在某些受试者中骨可能起作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Absorptive hypercalciuria (AH), characterized by excess intestinal calcium absorption, is a major cause of nephrolithiasis. Although bone loss is unexpected in this condition, it is common particularly in severe disease based on several bone density studies. Small studies have investigated iliac crest bone biopsies by histomorphometric analysis in hypercalciuric stone-formers, but the subjects were not fully characterized. Therefore, it is still unclear whether bone loss in severe AH is due to low formation or excess bone resorption and whether the bone contributes to the hypercalciuric state. The goal of this project is to better elucidate the pathophysiologic mechanisms for bone loss and hypercalciuria in severe AH to allow formulation of more rational treatment modalities. The hypotheses are 1) the main cause of bone loss in subjects with severe AH is reduced bone formation in the setting of normal or slightly increased bone resorption, and 2) hypercalciuria in severe AH is primarily caused by excessive intestinal calcium absorption, but the bone may contribute in some subjects.