MENTORED PATIENT-ORIENTED RESEARCH CAREER DEVELOPMENT AW

提案(改编自申请者的摘要)：啊，特征是过度 肠道钙吸收，是肾结石的主要原因。虽然 在这种情况下，骨丢失是意想不到的，几项骨密度研究已经 证明它是常见的，特别是在严重的疾病中。的目标是 这个项目是为了更好地阐明骨骼的病理生理机制。 失钙和高钙尿症在重症急性胰腺炎中的制定更加合理 治疗方式。研究人员的假设是：1)主要的 严重急性胰腺炎患者骨丢失的原因是骨形成减少。 骨吸收正常或轻度增加；2)高钙尿症 重度急性胰腺炎主要是由肠道钙吸收过多引起的， 但在一些受试者中，骨骼可能会对此起到作用。 在这项建议中，申请人将通过比较25个AH来检验每个假设 患者分为两个配对的对照组，25名正常志愿者和25名 固定的高钙尿症患者(一种由以下原因引起的高钙尿症模型 骨吸收增加)。假设1将使用骨骼进行检验 组织形态计量学(终点：骨形成和骨吸收的差异 指标)和骨转换标志物(终点：血清骨的差异 特异性碱性磷酸酶和尿中游离脱氧吡啶和N- 端肽)。假设2将通过两种不同的生理学方法进行探讨 挑战：1)磷酸纤维素钠(SCP)，一种吸收性能差的粉末 它会阻止肠道钙的吸收，将被用于评估 肠道对尿钙的贡献(终点：减少 尿钙(以毫克/天为单位)；2)能阻止骨吸收的药奈德磷酸盐， 将被用来检查骨骼对尿钙的贡献 (终点：尿钙减少，单位为毫克/天)。 受试者将有基线的住院评估，同时消耗恒定的 代谢性饮食含钙10 mmolNa 100 mmoP 25.8 mmolP评价 将包括血清化学、甲状旁腺激素(PTH)、维生素D 代谢物、骨周转标志物、24小时尿钙和钙 通过直接和间接测量的吸收和骨密度。他们 将在三天的治疗期间在门诊环境中进行重新评估 SCP持续代谢饮食。他们也将作为住院患者进行研究。 治疗两周和三个月后的恒定代谢饮食 使用阿伦磷酸钠。

PROPOSAL (Adapted from the applicant's abstract): 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 bone loss and hypercalciuria in severe AH to allow formulation of more rational treatment modalities. The investigators hypotheses are that: 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 proposal, the applicant 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 2 will be probed via two separate physiologic challenges of: 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) Nendronate, an agent that blocks bone resorption, will be used to examine the contribution of the bone to urinary calcium (endpoint: 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, parathyroid hormone (PTH), vitamin D metabolites, bone markers of turnover, 24-hour urinary calcium, and calcium absorption by direct and indirect measurements and bone mineral density. They will be reevaluated in an outpatient setting during three days of treatment with SCP on constant metabolic diet. They will also be studied as inpatients on constant metabolic diet after two weeks and after three months of treatment with alendronate.