Mentored Patient Oriented Research Career Development Aw

指导以患者为导向的研究职业发展Aw

• 批准号: 6394875
• 负责人: Nicola Abate
• 金额: $ 12.34万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-15 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6394875
• 关键词: alendronate; alkaline phosphatase; biopsy; blood chemistry; bone density; bone development; bone metabolism; calcium flux; calcium metabolism; clinical research; dietary calcium; dietary sodium; gastrointestinal absorption /transport; human subject; hypercalciuria; morphometry; osteoblasts; osteoclasts; parathyroid hormones; pathologic bone resorption; pathologic process; skeletal pharmacology; urinalysis; vitamin D; vitamin metabolism

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.

具有过量肠道钙吸收的特征是吸收性高钙尿症（AH）是肾石石症的主要原因。尽管在这种情况下骨质流失是出乎意料的，但几项骨密度研究表明，它尤其是在严重疾病中很常见。该项目的目的是更好地阐明严重吸收性高钙（AH）中一种损失的病理生理机制和高钙尿症，以允许制定更多理性的治疗方式。我们的假设是1）严重AH的受试者骨质流失的主要原因是在正常或略有增加的骨吸收的情况下骨骼形成减少，而2）严重AH中的高钙尿症主要是由于肠道钙的吸收过多而引起的，但是在某些受试者中，骨骼可能对其造成骨骼的贡献。在此方案中，我们将通过比较25例AH患者与两个匹配对照组，25名正常志愿者和25名固定过度过滤的患者（一种因骨吸收增加导致的高钙尿症的模型）来检验每个假设。假设1将使用骨骼组态图（终点：骨形成和吸收指数的差异）和骨转离标记（终点：血清骨骼特异性碱性磷酸酶和无尿液无尿液脱氧吡啶丁胺和N-耐肽的差异）进行测试。假设两个将通过两个独立的生理挑战进行探测：1）磷酸钠（SCP）是一种吸收不良的粉末，可阻断肠钙的吸收，以评估肠道对尿钙的贡献（端点：Mg/d中的尿中钙的减少）。 2）阻断骨吸收的αAldronate将用于检查骨骼对尿钙的贡献（终点：mg/d中尿钙的减少）。受试者将进行基线住院评估，同时食用持续的代谢饮食，其中含有10 mmol CA，100 mmol Na和25.8 mmolP。评估将包括血清化学，PTH，PTH，维生素D代谢物，失误的骨标记，24小时的尿液钙，尿液钙，钙，直接和间接吸收钙的钙，并通过直接和不脱离骨骼骨骼骨矿物质和骨骼矿物质denteries。在持续代谢饮食的SCP治疗的3天治疗中，他们将在门诊销售中重新评估它们。他们还将在2周和3个月治疗Alendronate治疗3个月后，将其作为住院医师作为住院患者进行研究。