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: 7531101
• 负责人: THOMAS L. NICKOLAS
• 金额: $ 17.55万
• 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/7531101
• 关键词: 3-Dimensional; Academic Medical Centers; Adult; Age; Area; Arts; 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; Hand; Hip Fractures; Hip region structure; Hormones; Image; Incidence; Individual; Kidney; Kidney Diseases; Knowledge; Measurement; Measures; Mechanics; Medical; Mentors; Metabolic Bone Diseases; Methods; Minerals; Morbidity - disease rate; Nephrology; Osteoporosis; Patients; Peripheral; Physical Dialysis; Predisposition; Prevalence; Public Health; Race; Receiver Operating Characteristics; Renal Osteodystrophy; Renal function; Reporting; Research Personnel; Resolution; Risk; Roentgen Rays; 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 quality; bone strength; bone turnover; career; improved; indexing; mortality; new technology; novel; radius bone structure; 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）患病率迅速增加，CKD患者的骨折发生率远高于一般人群。不幸的是，双能X线吸收测定法（DXA）对CKD患者骨折风险的预测比一般人群差，需要改进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）是一种表征皮质和小梁微结构的新技术。有限元分析（FEA）是骨强度的一种测量方法，可应用于HRpQCT数据集。本申请的假设是，CKD 3 - 5期与骨小梁和皮质微结构的进行性改变相关，骨小梁和皮质微结构的进行性改变降低了强度并增加了骨折易感性，在CKD患者中，HRpQCT与FEA结合将提供比DXA更好的骨折识别。我们将在150例CKD 3 - 5期受试者（75例骨折）的横断面研究中检验这一假设。在一个子集中，我们将验证HRpQCT测量，建立和新的骨转换标志物对经髂骨活检组织形态计量学。在CKD 4期受试者（n=50）中，我们将纵向评价骨微结构与肾功能变化的关系。本研究与公共卫生高度相关，因为CKD患者的骨折风险及其相关发病率和死亡率极高，且CKD和骨质疏松症高度相关。该项目也是我5年职业发展计划的培训平台，其目标是让我成为CKD-矿物质和骨骼疾病（MBD）领域的独立临床研究者。该计划包括放射成像，先进的生物统计学和流行病学方法的教学培训，HRpQCT，FEA和髂间骨活检定量组织形态学的具体实践培训，骨生物力学和骨细胞生物学领域的领先专家，以及与我的导师和合作导师，代谢性骨病和CKD-MBD领域的领导者经常会面。在获奖期间，我将开发使用这些工具评估CKD患者骨强度的专业知识。在第四年，我将开始计划提交RO 1。我在这个奖项期间获得的技能和知识将使我发展成为一个富有成效的，独立的调查员，具有在肾脏病学和内分泌学领域不寻常的技能。 公共卫生相关性：本研究与公共卫生高度相关，因为CKD患者的骨折风险及其相关发病率和死亡率极高，且CKD和骨质疏松症高度相关。