ROLE OF BONE IN ABSORPTIVE HYPERCALCIURIA

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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.