Mentored Patient Oriented Research Career Development Aw

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。虽然骨丢失在这种情况下是出乎意料的，但几项骨密度研究表明，这是常见的，特别是在严重的疾病中。本项目的目的是更好地阐明严重吸收性高钙尿症（AH）中一个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。我们的假设是：1）重度AH受试者中骨丢失的主要原因是在骨吸收正常或轻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，骨可能对此有贡献。在本方案中，我们将通过比较25名AH患者与两个匹配的对照组（25名正常志愿者和25名固定的高钙尿症患者（骨吸收增加导致的高钙尿症模型））来检验每个假设。将使用骨组织形态计量学（终点：骨形成和吸收指数的差异）和骨转换标志物（终点：血清骨特异性碱性磷酸酶和尿游离脱氧吡啶啉和N-端肽的差异）检验假设1。假设2将通过两个单独的生理挑战进行探讨：1）将使用纤维素磷酸钠（SCP）（一种吸收不良的粉末，可阻断肠钙吸收）评估肠对尿钙的贡献（终点：尿钙减少（mg/d））。2)阿仑膦酸盐可阻断骨吸收，将用于检查骨对尿钙的贡献（终点：尿钙减少，单位为mg/d）。受试者将接受基线住院评价，同时摄入含有10 mmol Ca、100 mmol Na和25.8 mmol P的恒定代谢饮食。评价将包括血清化学、PTH、维生素D代谢物、骨转换标志物、24小时尿钙、通过直接和间接测量的钙吸收和骨矿物质密度。在持续代谢饮食的SCP治疗3天期间，将在门诊销售中对其进行重新评价。他们也将在阿仑膦酸钠治疗2周和3个月后作为恒定代谢饮食的住院患者进行研究。

Absorptive hypercalciuria (AH), characterized by excess intestinal calcium absorption, is a major cause of nephrolithiasis. Although bone loss is unexpected in this condition, several bone density studies have demonstrated that it is common particularly in severe disease. The goal of this project is to better elucidate the pathophysiologic mechanisms for one loss and hypercalciuria in severe absorptive hypercalciuria (AH) to allow formulation of more rational treatment modalities. Our 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 to it in some subjects. In this protocol, we will test each hypothesis by comparing 25 AH patients with two matching control groups, 25 normal volunteers and 25 immobilized hypercalciuric patients (a model for hypercalciuria resulting from increased bone resorption). Hypothesis 1 will be tested using bone histomorphometry (endpoints: difference in bone formation and resorption indices) and bone turnover markers (endpoints: difference in serum bone specific alkaline phosphatase and urine free deoxypyridinoline and N-telopeptides). Hypothesis two will be probed via two separate physiologic challenges: 1) sodium cellulose phosphate (SCP), a poorly absorbed powder which blocks intestinal calcium absorption, will be used to assess the contribution of the intestine to urinary calcium (endpoint: decrement in urinary calcium in mg/d). 2) Alendronate, which blocks bone resorption, will be used to examine the contribution of the bone to urinary calcium (end point: decrement in urinary calcium in mg/d). Subjects will have baseline inpatient evaluation while consuming a constant metabolic diet containing 10 mmol Ca, 100 mmol Na and 25.8 mmol P. Evaluation will include serum chemistries, PTH, vitamin D metabolites, bone markers of turnover, 24-hour urinary calcium, calcium absorption by direct and indirect measures and bone mineral density. They will be reevaluated in an outpatient selling during 3 days of treatment with SCP on constant metabolic diet. They will also be studied as inpatients on constant metabolic diet after 2 weeks and after 3 months of treatment with alendronate.