Research Project Core 1

研究项目核心1

• 批准号: 10241469
• 负责人: Michelle Denburg
• 金额: $ 10.5万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-18 至 2022-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10241469
• 关键词: 18 year old; 19 year old; Adolescence; Adolescent; Adult; Affect; Age; Atherosclerosis; Biomechanics; Biopsy; Blood Pressure; Blood Vessels; Body mass index; Bone Density; Bone Mineral Contents; Bone Resorption; Bone remodeling; Bone structure; Calcium; Cardiovascular system; Carotid Atherosclerotic Disease; Case Series; Child; Childhood; Chronic; Citrates; Data; Development; Devices; Diabetes Mellitus; Dietary Assessment; Dietary Calcium; Disease; Disease Marker; Dual-Energy X-Ray Absorptiometry; Elderly; Endothelium; Event; Excretory function; Failure; Female; Finite Element Analysis; Fracture; Future; Generations; Growth; Health; Height; Hip region structure; Homeostasis; Hour; Hypertension; Image; Impairment; Incidence; Individual; Intervention Trial; Kidney; Kidney Calculi; Link; Measures; Metabolic; Metabolism; Minerals; Modeling; Morbidity - disease rate; Multi-Institutional Clinical Trial; Myocardial Infarction; Nephrology; Osteogenesis; Outcome; Peripheral; Physiologic pulse; Population; Population Study; Prospective cohort study; Radial; Renal function; Research Project Grants; Resolution; Resources; Risk; Risk Factors; Site; Skeleton; Smoking; Sodium; Stroke; Structure; Testing; Thick; Time trend; Uric Acid; Urinary Calculi; Urine; Vascular Diseases; Vertebral column; Vitamin D; Work; X-Ray Computed Tomography; age group; arterial stiffness; base; bone; bone imaging; bone mass; bone quality; bone strength; calcification; cardiovascular risk factor; carotid intima-media thickness; comorbidity; dietary; fracture risk; hypercalciuria; imaging modality; indexing; insight; male; mineralization; multidisciplinary; population based; prospective; protein intake; sex; skeletal; tibia; young adult

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.

项目1摘要 尿石病（USD）很常见，并且越来越被骨骼的慢性全身性疾病。 和血管发病率。最近基于人群的数据表明这种发病率启动了，甚至可能更多 在生命之后发音。在青少年中，美元的事件越来越不成比例 了解其对该人群中骨骼和血管健康的影响至关重要。此外，研究 USD中的骨血管连接的成人有限，儿童缺乏研究，以及对儿童的研究 减轻成年人高度普遍存在的混淆合并条件的优势。 确定损害骨骼强度和血管健康的可修改因素将有助于发展 降低整个生命过程中断裂率和心血管事件的策略。的主要目标 这项研究是：（1）评估美元对青少年骨密度，结构和强度增益的影响 并通过尿液代谢分析和饮食来确定骨强度变化的可修改预测指标 评估和（2）确定USD是否与亚临床血管疾病以及血管标记有关 疾病与USD的青少年中的骨骼强度较低有关。 拟议的工作将利用我们多学科的小儿肾结石中心的资源，合并 使用最先进的骨成像方法和血管措施进行首次前瞻性队列研究 有125名青少年（10-19岁）和125的青少年（10-19岁）的骨质和早期标记 与年龄，性别和体重指数相匹配的健康对照，紧随其后的是24个月。新的第二 生成高分辨率外围定量计算机断层扫描（HR-PQCT）设备将用于 评估骨微体系结构和微限定元素分析（µFEA）骨强度估计（衰竭负荷） 与离体生物力学测试高度相关。血管评估将结合 动脉僵硬（脉搏波速度/分析），亚临床动脉粥样硬化（颈动脉内膜厚度）和 内皮功能（内尾），所有这些功能都已证明是独立预测心血管事件的 成年人。我们还将确定在多个位点的DXA测量是否在 身体，脊柱，臀部和半径）反射骨骼定义由HR-PQCT捕获并与血管标记相关 疾病。这将是第一项在成人或 有美元的孩子。同时进行的纵向尿液代谢分析，三天24小时饮食 召回和维生素D相关矿物质代谢的全面衡量标准将允许评估 预测因子包括尿钙，柠檬酸盐和尿酸排泄，饮食钙，钠和蛋白质摄入， 并改变了维生素D和矿物质稳态。这项研究的结果将专门用于告知未来 多中心临床试验，以促进美元青少年促进骨骼和血管健康的干预措施。