Mentored Patient Oriented Research Career Development Aw

指导以患者为导向的研究职业发展Aw

基本信息

批准号：
6159466
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
项目类别：
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

项目摘要

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.

吸收性高钙尿症（AH）以肠道钙吸收过多为特征，是肾结石的主要原因。尽管在这种情况下骨质流失是出乎意料的，但一些骨密度研究表明，这种情况很常见，尤其是在严重疾病中。该项目的目标是更好地阐明严重吸收性高钙尿症（AH）中一种丢失和高钙尿症的病理生理机制，以便制定更合理的治疗方式。我们的假设是 1) 严重 AH 受试者骨质流失的主要原因是在骨吸收正常或略有增加的情况下骨形成减少，2) 严重 AH 患者的高钙尿症主要是由肠道钙吸收过多引起，但骨吸收可能会在某些科目上有所贡献。在本协议中，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）来测试假设1。假设二将通过两个单独的生理挑战进行探讨：1）纤维素磷酸钠（SCP）是一种吸收不良的粉末，会阻碍肠道钙的吸收，将用于评估肠道对尿钙的贡献（终点：尿钙减少）以毫克/天为单位）。 2) 阿仑膦酸钠可阻止骨吸收，用于检查骨对尿钙的贡献（终点：尿钙减少量（毫克/天））。受试者将接受基线住院评估，同时摄入含有 10 mmol Ca、100 mmol Na 和 25.8 mmol P 的恒定代谢饮食。评估将包括血清化学、PTH、维生素 D 代谢物、骨代谢标志物、24 小时尿钙、钙吸收通过直接和间接测量以及骨矿物质密度。在 SCP 持续代谢饮食治疗的 3 天期间，他们将在门诊接受重新评估。他们还将作为接受阿仑膦酸钠治疗 2 周和 3 个月后持续代谢饮食的住院患者进行研究。