Research Project Core 1

项目1摘要 尿路结石病是一种常见的慢性骨骼疾病，已被越来越多的人认识到。 和血管发病率。最近基于人群的数据表明，这种发病率开始于，甚至可能更高 在生命周期的早期就被宣告了。在青少年中，美元兑美元的发病率正在不成比例地增加， 因此，了解其对这一人群的骨骼和血管健康的影响至关重要。此外，研究 在美国，骨与血管的联系仅限于成人，在儿童中缺乏，而对儿童的研究表明 在缓解成人中高度普遍的混杂合并症方面的优势。 找出影响骨骼强度和血管健康的可修改因素将促进发展 在整个生命周期内减少骨折发生率和心血管事件的策略。的主要目标 本研究旨在：(1)评估美元对青少年骨密度、结构和强度增长的影响。 并通过尿代谢谱和饮食确定骨强度变化的可修改预测因子 评估和(2)确定美元是否与亚临床血管疾病相关，以及血管标记物 在患有美元的青少年中，疾病与骨强度降低有关。 拟议的工作将利用我们的多学科儿科肾结石中心的资源，结合 使用最先进的骨成像方法和血管测量，进行首个前瞻性队列研究 125名患有美元和125名10-19岁青少年的骨质量和血管疾病早期标志物 在年龄、性别和体重指数方面匹配的健康对照组，在24个月的间隔内进行跟踪。新的2号 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 评估骨微结构和微有限元分析(µFEA)对骨强度(破坏载荷)的估计 这与体外生物力学测试高度相关。血管评估将结合标记物 动脉僵硬(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)，以及 内皮功能(内毒素)，所有这些都被证明可以独立地预测心血管事件 成年人。我们还将确定DXA是否测量多个部位的面骨密度和骨矿含量(整体 身体、脊柱、髋部和桡骨)反映HR-pQCT捕捉到的骨缺陷，并与血管标记物相关 疾病。这将是第一项在成人或青少年中进行重复骨骼和血管测量的研究。 患有美元的儿童。同步纵向尿液代谢谱分析，三天24小时饮食 召回，以及维生素D相关矿物质代谢的综合测量将允许评估 预测指标包括尿钙、柠檬酸和尿酸排泄量、膳食钙、钠和蛋白质摄入量， 改变了维生素D和矿物质的动态平衡。这项研究的结果将特别为将来提供信息 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美元。

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.