Bone Quality and Mechanical Competence In Chronic Kidney Disease

慢性肾脏病的骨质量和机械能力

• 批准号: 8130994
• 负责人: THOMAS L. NICKOLAS
• 金额: $ 17.54万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8130994
• 关键词: 3-Dimensional; Academic Medical Centers; Adult; Age; Area; Award; Biological Markers; Biomechanics; Biometry; Biopsy; Biopsy Specimen; Body mass index; Bone Density; Bone Diseases; Bone remodeling; Cellular biology; Characteristics; Chronic Kidney Failure; Clinical Investigator; Competence; Cross-Sectional Studies; Data Set; Deterioration; Development Plans; Diagnostic tests; Dialysis patients; Dialysis procedure; Discrimination; Dual-Energy X-Ray Absorptiometry; End stage renal failure; Endocrinology; Epidemiologic Methods; Evolution; Finite Element Analysis; Fracture; Functional disorder; Gender; General Population; Goals; Gold; Health; Hip Fractures; Hip region structure; Hormones; Image; Incidence; Individual; Kidney; Knowledge; Measurement; Measures; Mechanics; Medical; Mentors; Metabolic Bone Diseases; Minerals; Morbidity - disease rate; Nephrology; Osteoporosis; Patients; Peripheral; Predisposition; Prevalence; Public Health; Race; Radial; Receiver Operating Characteristics; Renal Osteodystrophy; Renal function; Reporting; Research Personnel; Resolution; Risk; Scanning; Sensitivity and Specificity; Serum Markers; Severities; Severity of illness; Site; Staging; Structure; Techniques; Technology; Testing; Thick; Training; Vertebral column; X-Ray Computed Tomography; bone; bone cell; bone mass; bone quality; bone strength; bone turnover; career development; high risk; imaging modality; improved; indexing; meetings; mortality; new technology; novel marker; skills; substantia spongiosa; tibia; tool; ultra high resolution

DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) prevalence is increasing rapidly and fracture incidence is much higher in patients with CKD than in the general population. Unfortunately, fracture risk prediction by dual energy X-ray absorptiometry (DXA) is poorer among CKD patients than in the general population and improved imaging methods are necessary to evaluate their fracture susceptibility. Ultra high resolution peripheral quantitative computed tomography (HRpQCT; resolution 80-100 um) is a novel technology that characterizes both cortical and trabecular microarchitecture. Finite element analysis (FEA), a measure of bone strength, can be applied to HRpQCT data sets. The hypotheses of this application are that CKD stages 3 to 5 are associated with progressive alterations in trabecular and cortical microarchitecture that reduce strength and increase fracture susceptibility, and HRpQCT with FEA, will provide greater fracture discrimination than DXA in patients with CKD. We will test this hypothesis in a cross-sectional study of 150 subjects with CKD stages 3 to 5 (75 with fracture). In a subset, we will validate HRpQCT measurements, established and novel markers of bone turnover against histomorphometry of transiliac bone biopsies. In CKD stage 4 subjects (n=50) we will longitudinally evaluate bone microarchitecure in relation to changes in kidney function. This study is highly relevant to public health, as fracture risk and its associated morbidity and mortality are exceedingly high in CKD patients and CKD and osteoporosis are highly coprevalent. This project also forms the training platform of my 5-year career development plan, the goal of which is to allow me to become an independent clinical investigator in the field of CKD-mineral and bone disorders (MBD). The plan includes didactic training in radiographic imaging, advanced biostatistics and epidemiological methods, specific hands-on training in HRpQCT, FEA and quantitative histomorphometry of transiliac bone biopsies with leading experts in the fields of bone biomechanics and bone cell biology, and frequent meetings with my mentor and co-mentor, leaders in the field of metabolic bone disease and CKD-MBD. During the award, I will develop expertise in using these tools to assess bone strength in CKD patients. In the fourth year, I will begin planning an RO1 submission. The skills and knowledge I acquire during this award will allow me to develop into a productive, independent investigator with a skill set that is unusual in the fields of nephrology and endocrinology. PUBLIC HEALTH RELEVANCE: This study is highly relevant to public health, as fracture risk and its associated morbidity and mortality are exceedingly high in CKD patients and CKD and osteoporosis are highly coprevalent.

描述（由申请人提供）： 慢性肾脏病（CKD）患病率正在迅速增加，CKD 患者的骨折发生率远高于普通人群。不幸的是，通过双能 X 射线吸收测定法 (DXA) 预测 CKD 患者的骨折风险比一般人群差，因此需要改进的成像方法来评估其骨折易感性。超高分辨率外周定量计算机断层扫描（HRpQCT；分辨率 80-100 um）是一项表征皮质和小梁微结构的新技术。有限元分析 (FEA) 是一种骨强度测量方法，可应用于 HRpQCT 数据集。本申请的假设是，CKD 3 至 5 期与小梁和皮质微结构的进行性改变相关，从而降低强度并增加骨折易感性，并且 HRpQCT 结合 FEA 将为 CKD 患者提供比 DXA 更好的骨折辨别能力。我们将在 150 名 CKD 3 至 5 期受试者（其中 75 名患有骨折）的横断面研究中检验这一假设。在一个子集中，我们将根据经髂骨活检的组织形态计量学验证 HRpQCT 测量、已建立的和新的骨转换标志物。在 CKD 4 期受试者 (n=50) 中，我们将纵向评估骨微结构与肾功能变化的关系。这项研究与公众健康高度相关，因为 CKD 患者的骨折风险及其相关发病率和死亡率极高，而且 CKD 和骨质疏松症非常普遍。这个项目也构成了我5年职业发展计划的培训平台，其目标是让我成为CKD-矿物质和骨疾病（MBD）领域的独立临床研究者。该计划包括放射成像、先进生物统计学和流行病学方法方面的教学培训，与骨生物力学和骨细胞生物学领域的领先专家一起进行 HRpQCT、FEA 和经髂骨活检定量组织形态计量学方面的具体实践培训，以及与我的导师和合作导师、代谢性骨疾病和 CKD-MBD 领域的领导者的频繁会面。在获奖期间，我将发展使用这些工具评估 CKD 患者骨强度的专业知识。第四年，我将开始计划 RO1 提交。我在这个奖项中获得的技能和知识将使我能够发展成为一名富有成效的独立研究者，拥有肾脏病学和内分泌学领域不寻常的技能。 公众健康相关性：这项研究与公众健康高度相关，因为 CKD 患者的骨折风险及其相关发病率和死亡率非常高，而且 CKD 和骨质疏松症非常普遍。