ROLE OF BONE IN ABSORPTIVE HYPERCALCIURIA

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。以肠道钙吸收过多为特征的吸收性高钙尿症(AH)是肾结石的主要原因。尽管骨丢失在这种情况下是意想不到的，但根据几项骨密度研究，这种情况在严重疾病中尤其常见。一些小研究通过组织形态计量学分析对高钙尿性结石患者的髂骨骨活检进行了研究，但受试者的特征尚不完全明确。因此，目前尚不清楚重度急性胰腺炎患者的骨丢失是由于骨形成不足还是过度骨吸收所致，也不清楚骨是否导致了高钙尿状态。本项目的目标是更好地阐明重症急性脑出血患者骨丢失和高钙尿的病理生理机制，以便制定更合理的治疗方案。假设1)重度AH患者骨丢失的主要原因是骨吸收正常或轻度增加时骨形成减少，2)重度AH患者高钙尿症主要是由肠道钙吸收过多引起的，但部分患者的骨骼也有贡献。

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.