Metabolomic & Radiographic Markers of Fracture Risk Among Older Adults with Diabetes

代谢组学

• 批准号: 10333346
• 负责人: Richard Hsang-Yang Lee
• 金额: $ 8.93万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-15 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10333346
• 关键词: 3-Dimensional; Abdomen; Address; Adult; Affect; Age; American; Area; Biological Markers; Biomechanics; Body mass index; Bone Density; Branched-Chain Amino Acids; Cardiovascular Diseases; Case-Control Studies; Chronic; Clinical; Clinical Assessment Tool; Clinical Data; Clinical assessments; Communities; Complications of Diabetes Mellitus; Contralateral; County; Data; Development; Diabetes Mellitus; Diagnostic; Disease; Dual-Energy X-Ray Absorptiometry; Elderly; Endocrinologist; Epidemiology; Etiology; Femur; Fostering; Fracture; Gender; Glycosylated hemoglobin A; Goals; Health; Hip Fractures; Hip region structure; Individual; Intervention; Laboratories; Length; Measures; Mediating; Medical; Metabolic; Metabolic Bone Diseases; Metabolic Marker; Metabolic dysfunction; Methods; Minerals; Modulus; Morbidity - disease rate; Neck; Nested Case-Control Study; Non-Insulin-Dependent Diabetes Mellitus; North Carolina; Participant; Pelvis; Peripheral Nervous System Diseases; Pharmaceutical Preparations; Population; Positioning Attribute; Prevention; Prevention strategy; Public Health; Publishing; Questionnaires; Renal function; Reporting; Research; Research Activity; Research Personnel; Resources; Risk; Sampling; Scanning; Serum; Societies; Source; Statistical Data Interpretation; Techniques; Technology; Testing; Tissues; Training; Translational Research; Trauma; United States National Institutes of Health; Urine; Woman; Work; acylcarnitine; adjudicate; base; biomechanical engineering; biomechanical test; bone; bone health; bone quality; bone strength; career development; clinical biomarkers; clinical development; clinical epidemiology; clinical risk; cohort; comorbidity; computerized; diabetic; epidemiology study; fall risk; falls; fracture risk; high resolution imaging; improved; innovation; materials science; medical complication; meetings; men; metabolomics; mortality; novel marker; osteoporosis with pathological fracture; personalized medicine; prevent; radiological imaging; reconstruction; research clinical testing; risk stratification; screening; skills; stem; symposium; tool

ABSTRACT Among its medical complications, type 2 diabetes mellitus in older adults is associated with a two-fold increase in the risk of hip and other low-trauma bone fractures. Paradoxically, this increased risk occurs despite a higher average bone mineral density. This increased fracture risk is likely multifactorial, stemming from metabolic dysfunction that results in both increased falls risk and decreased bone strength. However, fracture risk stratification currently is limited largely to bone density testing and clinical risk tools that do not perform adequately for adults with diabetes. Because bone is both a metabolic and structural tissue, metabolomics and biomechanical analyses would be particularly useful for developing and assessing new measures of fracture risk. The objective of this application is to develop and evaluate radiographic and laboratory biomarkers of fracture risk among older adults with diabetes, utilizing biomechanical and translational measures. The proposed research has the following aims: 1) Determine the association between metabolomic profiles and incident clinical fracture among older adults with diabetes; 2) Compare geometric and biomechanical measures at the femoral neck and intertrochanteric region among older adults with diabetes, with and without hip fracture. This application builds upon the prior published work and clinical expertise of the Principle Investigator, Dr. Richard Lee, and provides him additional research skills to assist with his career development goal of understanding the interaction of chronic medical conditions on the bone health of older adults, focusing on diabetes. Dr. Lee is a dual-trained Geriatrician and Endocrinologist with expertise in metabolic bone disease. The primary training goals of this proposal include the following: 1) Develop laboratory and analytical skills in translational science that will be used in the development and evaluation of clinical biomarkers, including –omics technologies; 2) Acquire principles and skills in biomechanical engineering and materials science to integrate with clinical and epidemiological analyses. By integrating biomechanical engineering and metabolomics approaches with epidemiologic research to identify new markers of fracture risk, this application addresses a significant source of morbidity and mortality among an increasing proportion of older adults.

抽象的 在其医疗并发症中，老年人的2型糖尿病与 髋关节和其他低创伤骨骨折的风险增加了两倍。矛盾的是，这 尽管平均骨矿物质密度较高，但仍会增加风险。这增加了断裂 风险可能是多因素的，这是由于代谢功能障碍而导致两者增加 跌落风险并扩大骨骼强度。但是，当前断裂风险分层有限 在很大程度上是针对成年人表现不佳的骨密度测试和临床风险工具 糖尿病。因为骨骼既是代谢组织和结构性组织，代谢组学和 生物力学分析对于开发和评估新的分析特别有用 骨折风险的度量。该应用的目的是开发和评估 糖尿病老年人骨折风险的X线照相和实验室生物标志物， 利用生物力学和翻译的测量。拟议的研究具有以下 目的：1）确定代谢组分布与入射临床骨折之间的关联 在糖尿病的老年人中； 2）在比较几何和生物力学测量 糖尿病老年人的股骨颈和跨金融区，有和没有髋关节 断裂。该应用程序建立在先前已发表的工作和临床专业知识的基础上 主要调查员理查德·李（Richard Lee）博士，并为他提供了其他研究技能，以协助 他的职业发展目标是了解慢性病条件在 老年人的骨骼健康，重点是糖尿病。李博士是一名双重训练的老年医生， 内分泌学家具有代谢骨病的专业知识。主要培训目标 建议包括以下内容：1）发展转化科学的实验室和分析技能 这将用于临床生物标志物的开发和评估，包括 - 技术； 2）获取生物力学工程和材料的原则和技能 与临床和流行病学分析相结合的科学。通过整合生物力学 通过流行病学研究来识别新标记的工程和代谢组学方法 骨折风险，该申请解决了重要的发病率和死亡的重要来源 老年人比例越来越多。

项目成果

Diabetes is associated with a lower minimum moment of inertia among older women: An analysis of 3D reconstructions of clinical CT scans.

• DOI: 10.1016/j.jbiomech.2021.110707
• 发表时间: 2021-11-09
• 期刊: JOURNAL OF BIOMECHANICS
• 影响因子: 2.4
• 作者: Heckelman, Lauren N.;Wesorick, Benjamin R.;DeFrate, Louis E.;Lee, Richard H.
• 通讯作者: Lee, Richard H.

The break in FRAX: Equity concerns in estimating fracture risk in racial and ethnic minorities.

• DOI: 10.1111/jgs.17316
• 发表时间: 2021-09
• 期刊: JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
• 影响因子: 6.3
• 作者: Reid, Hadley W.;Selvan, Bharathi;Batch, Bryan C.;Lee, Richard H.
• 通讯作者: Lee, Richard H.