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: 8304308
• 负责人: THOMAS L. NICKOLAS
• 金额: $ 17.69万
• 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/8304308
• 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）： CKD患者的慢性肾脏疾病（CKD）患病率正在迅速增加，骨折的发生率要高得多。不幸的是，CKD患者的双能X射线吸收法（DXA）的断裂风险预测比一般人群差，并且需要改进的成像方法来评估其骨折易感性。超高分辨率外围定量计算机断层扫描（HRPQCT;分辨率80-100 UM）是一种具有皮质和小梁微体系结构的新技术。有限元分析（FEA）是骨强度的度量，可以应用于HRPQCT数据集。该应用的假设是CKD阶段第3至5阶段与小梁和皮质微体系结构的进行性改变有关，这些阶段降低了强度并提高断裂易感性，而使用FEA的HRPQCT则将提供比CKD患者更大的断裂歧视。我们将在150名CKD阶段3至5的受试者的横截面研究中检验这一假设（75个骨折）。在子集中，我们将验证HRPQCT测量值，骨转换的骨转换标记和新颖的标志物，以针对跨性骨活检的组织形态计量学。在CKD阶段4受试者（n = 50）中，我们将纵向评估与肾脏功能变化有关的骨微体系环。这项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的发病率和死亡率极高，CKD和骨质疏松症具有很高的副本。该项目还构成了我5年职业发展计划的培训平台，其目的是让我成为CKD-Mineral和骨骼疾病（MBD）领域的独立临床研究者。 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.在奖励期间，我将在使用这些工具来评估CKD患者的骨骼强度方面发展专业知识。在第四年，我将开始计划RO1提交。我在此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，其技能在肾脏学和内分泌学领域很不寻常。 公共卫生相关性：这项研究与公共卫生高度相关，因为CKD患者的断裂风险及其相关的发病率和死亡率极高，CKD和骨质疏松症具有很高的副本。

项目成果

Can one evaluate bone disease in chronic kidney disease without a biopsy?

• DOI: 10.1097/01.mnh.0000447014.36475.58
• 发表时间: 2014-07-01
• 期刊: CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION
• 影响因子: 3.2
• 作者: Babayev, Revekka;Nickolas, Thomas L.
• 通讯作者: Nickolas, Thomas L.

Comprehensive Associations between Acidosis and the Skeleton in Patients with Kidney Disease.

肾病患者酸中毒与骨骼之间的综合关联。

• DOI: 10.1681/asn.0000000000000085
• 发表时间: 2023
• 期刊: Journal of the American Society of Nephrology : JASN
• 作者: Levy,RebeccaV;McMahon,DonaldJ;Agarwal,Sanchita;Dempster,David;Zhou,Hua;Misof,BarbaraM;Guo,XE;Kamanda-Kosseh,Mafo;Aponte,MariaAlejandra;Reidy,Kimberly;Kumar,Juhi;Fusaro,Maria;Brown,DenverD;Melamed,MichalL;Nickolas,Thomas
• 通讯作者: Nickolas,Thomas