Research Project Core 1

项目1摘要 泌尿系结石病（USD）是一种常见的慢性全身性疾病， 和血管发病率。最近基于人口的数据表明，这种发病率开始，甚至可能更多 在生命的早期阶段就已经出现了USD的发病率在青少年中不成比例地增加， 因此了解其对该人群骨骼和血管健康的影响至关重要。此外，研究 的骨血管联系在USD是有限的，在成人和缺乏儿童，和儿童的研究赋予 在减轻成人中高度流行的混杂共病状况方面的优势。 确定影响骨强度和血管健康的可改变因素将促进骨组织的发展。 降低整个生命过程中骨折率和心血管事件的策略。的主要目标 本研究的目的是：（1）评价USD对青少年骨密度、结构和强度的影响 并通过尿液代谢分析和饮食分析来确定骨强度变化的可修改预测因素， 评估和（2）确定USD是否与亚临床血管疾病相关，以及血管病变的标志物是否与亚临床血管疾病相关。 疾病与USD青少年的骨强度降低有关。 拟议的工作将利用我们的多学科儿童肾结石中心的资源，结合 采用最先进的骨成像方法和血管测量，进行第一项前瞻性队列研究， 骨质量和血管疾病的早期标志物在125名青少年（10-19岁）与USD和125 年龄、性别和体重指数匹配的健康对照组，随访24个月。新第二 新一代高分辨率外周定量计算机断层扫描（HR-pQCT）设备将用于 评估骨微结构和骨强度（失效载荷）的微有限元分析（µFEA）估计值 与离体生物力学测试高度相关。血管评估将结合以下联合收割机标记物： 动脉硬度（脉搏波速度/分析），亚临床动脉粥样硬化（颈动脉内膜中层厚度），和 内皮功能（EndoPAT），所有这些都已被证明是独立预测心血管事件， 成年人了我们还将确定是否DXA测量区域BMD和骨矿物质含量在多个地点（整个 身体、脊柱、髋关节和桡骨）反映HR-pQCT捕获的骨缺损，并与血管标记物相关。 疾病这将是第一项前瞻性地在成人中进行重复骨和血管测量的研究， 儿童USD 3天24小时饮食中通过Litholink进行的同步纵向尿液代谢分析 召回，维生素D相关矿物质代谢的综合措施将允许评估 预测因子包括尿钙、柠檬酸盐和尿酸排泄，膳食钙、钠和蛋白质摄入， 改变了维生素D和矿物质的体内平衡这项研究的结果将专门用于告知未来 多中心临床试验的干预措施，以促进骨积累和血管健康的青少年与USD。

PROJECT 1 ABSTRACT Urinary stone disease (USD) is common and increasingly recognized as a chronic systemic disorder with skeletal and vascular morbidity. Recent population-based data suggest this morbidity starts, and may even be more pronounced, early in the lifecourse. The incidence of USD is increasing disproportionately among adolescents, making it critical to understand its impact on bone and vascular health in this population. Furthermore, studies of the bone-vascular link in USD are limited in adults and lacking in children, and the study of children confers advantages in mitigating against confounding co-morbid conditions that are highly prevalent among adults. Identifying modifiable factors that compromise bone strength and vascular health will facilitate the development of strategies to reduce fracture rates and cardiovascular events across the lifecourse. The primary objectives of this study are to: (1) evaluate the impact of USD on gains in bone density, structure and strength in adolescents and identify modifiable predictors of changes in bone strength via urine metabolic profiling and dietary assessment and (2) determine if USD is associated with subclinical vascular disease and if markers of vascular disease are associated with lower bone strength in adolescents with USD. The proposed work will leverage the resources of our multidisciplinary Pediatric Kidney Stone Center, combined with state-of-the-art bone imaging methods and vascular measures, to conduct the first prospective cohort study of bone quality and early markers of vascular disease in 125 adolescents (10-19 years old) with USD and 125 healthy controls matched on age, sex, and body mass index, followed over a 24 month interval. The new 2nd generation high-resolution peripheral quantitative computed tomography (HR-pQCT) device will be used to assess bone microarchitecture and micro-finite element analysis (µFEA) estimates of bone strength (failure load) that are highly correlated with ex vivo biomechanical testing. Vascular assessment will combine markers of arterial stiffness (pulse wave velocity/analysis), subclinical atherosclerosis (carotid intima-media thickness), and endothelial function (EndoPAT), all of which have been shown to independently predict cardiovascular events in adults. We will also determine if DXA measures of areal BMD and bone mineral content at multiple sites (whole body, spine, hip and radius) reflect bone deficits captured by HR-pQCT and correlate with markers of vascular disease. This will be the first study to perform repeated bone and vascular measures prospectively in adults or children with USD. Concurrent longitudinal urine metabolic profiling by Litholink, three day 24-hour dietary recalls, and comprehensive measures of vitamin D-related mineral metabolism will allow for assessment of predictors including urine calcium, citrate, and uric acid excretion, dietary calcium, sodium and protein intake, and altered vitamin D and mineral homeostasis. The results of this study will serve specifically to inform future multicenter clinical trials of interventions to promote bone accrual and vascular health in adolescents with USD.