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

摘要 在其医学并发症中，老年人中的2型糖尿病与 髋部和其他低创伤骨折的风险增加两倍。矛盾的是，这 尽管平均骨矿密度较高，但风险仍会增加。这一增加的骨折 风险可能是多因素的，源于代谢功能障碍，导致两者都增加 跌倒的风险和骨骼强度下降。然而，骨折风险分层目前是有限的。 很大程度上是由于骨密度测试和临床风险工具不适合成年人使用 患有糖尿病。因为骨骼既是代谢组织又是结构组织，代谢组学和 生物力学分析对于开发和评估新的 骨折风险的衡量标准。此应用程序的目标是开发和评估 老年糖尿病患者骨折风险的放射学和实验室生物标记物 利用生物力学和平移措施。拟议的研究有以下几个方面 目的：1)确定代谢组特征与发生的临床骨折之间的关联 在患有糖尿病的老年人中；2)比较几何和生物力学测量 老年糖尿病患者的股骨颈和粗隆间区域，有无髋关节 骨折。此应用程序建立在先前发布的工作和临床专业知识的基础上 首席调查员理查德·李博士，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疾病的相互作用 老年人的骨骼健康，重点是糖尿病。李医生是一名受过双重训练的老年科医生 在代谢性骨病方面有专长的内分泌学家。它的主要培训目标是 建议包括以下内容：1)培养翻译科学的实验室和分析技能 将用于临床生物标记物的开发和评估，包括组学 技术；2)掌握生物力学工程和材料的原理和技能 科学与临床和流行病学分析相结合。通过整合生物力学 工程和代谢组学方法与流行病学研究相结合以确定新的标志物 对于骨折风险，这项应用解决了以下人群的发病率和死亡率的一个重要来源 老年人的比例越来越高。

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.