Volumetric bone density, geometry, strength and bone tissue material properties in type 1 diabetes

1 型糖尿病的体积骨密度、几何形状、强度和骨组织材料特性

• 批准号: 9918247
• 负责人: Viral N Shah
• 金额: $ 16.72万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-10 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9918247
• 关键词: 3-Dimensional; Address; Adult; Affect; Age; Animal Model; Biopsy; Biopsy Specimen; Body mass index; Bone Density; Bone Tissue; Bone structure; Caring; Chemicals; Clinical; Clinical Sciences; Complications of Diabetes Mellitus; Data; Deterioration; Development; Diabetes Mellitus; Doctor of Philosophy; Elasticity; Elderly; Electron Microscopy; Elements; Epidemiology; Femur; Financial Hardship; Finite Element Analysis; Fracture; Funding; Future; Gender; Geometry; Goals; Grant; Hip Fractures; Hip region structure; Human; Image; Insulin-Dependent Diabetes Mellitus; Intervention; Knowledge; Literature; Measures; Mentored Patient-Oriented Research Career Development Award; Mentors; Modeling; Morbidity - disease rate; Osteoporosis; Patients; Population; Postmenopause; Prevention approach; Property; Raman Spectrum Analysis; Reporting; Research; Research Personnel; Research Technics; Risk; Roentgen Rays; Senior Scientist; Site; Structure; Techniques; Testing; Therapeutic; Time; Tissues; Training; Translational Research; United States National Institutes of Health; Woman; Work; X-Ray Computed Tomography; base; biomechanical engineering; bone; bone aging; bone fragility; bone geometry; bone health; bone metabolism; bone quality; bone strength; career; career development; computerized; falls; fracture risk; high risk; high risk population; hip bone; improved; indexing; mortality; multimodality; nanoindentation; non-diabetic; novel; osteoporosis with pathological fracture; prevent; skills

Abstract Postmenopausal women with type 1 diabetes (T1D) have a six- to eight-fold higher risk for hip fractures compared to women without diabetes. Hip fractures are associated with significant morbidity, mortality, loss of independence, and financial burden. Moreover, hip fracture mortality is higher in patients with diabetes compared to subjects without diabetes. Dual x-ray absorptiometry (DXA), the most common test to assess bone health, measures only areal bone mineral density (BMD), and fails to provide information on bone quality; hence, it underestimates fracture risk in patients with T1D. Therefore, we hypothesize that hip structural and bone tissue material quality will be compromised in postmenopausal women with T1D compared to controls. Consistent with overarching hypothesis, we propose to determine hip bone structural quality (vBMD, bone geometry, and bone strength) using quantitative computed tomography (QCT) and a novel computerized image-based technique (finite element analysis) [Aim 1], and evaluate differences in bone tissue composition and tissue material properties from transiliac bone biopsy using Raman spectroscopy, nanoindentation, and backscattered electron microscopy [Aim 2] in postmenopausal women with T1D compared to age- and BMI- matched postmenopausal women without diabetes. With improved care, people with T1D are living longer and there is no specific approach for prevention and treatment of osteoporosis for older adults with T1D. Therefore, this study will elucidate possible mechanisms of bone fragility in postmenopausal women with T1D with the long-term goal to prevent hip fractures and related morbidity in this high-risk population. The proposed K23 award will facilitate my transition to independence by providing support necessary to; 1) acquire and consolidate clinical science knowledge and translational research skills; 2) develop professional research skills, and 3) develop a path to independent research. To achieve my professional goals, I have assembled a team of mentors comprised of 1) Dr. Janet Snell-Bergeon, PhD, an expert in the field of T1D complications and epidemiology, funded by the NIH for more than a decade; and 2) Dr. Wendy Kohrt, PhD, a senior scientist in the field of bone metabolism and aging, with over three decades of constant NIH funding. In addition, the expertise of Mentoring team (Dr. Chonchol, clinical researcher in the field of bone metabolism, Drs. Carpenter and Ferguson, biomechanical engineers and Dr. Pyle, biostatistician) will help advance my career in this field. The findings of the proposed study will generate essential data to propose an R01 focused on therapeutic strategies to reduce osteoporosis risk in T1D.

摘要 患有1型糖尿病（T1 D）的绝经后女性发生髋部骨折的风险高出6至8倍 与没有糖尿病的女性相比。髋关节骨折与显著的发病率、死亡率、 独立性和经济负担。此外，糖尿病患者的髋部骨折死亡率更高 与无糖尿病的受试者相比。双能X线吸收测定法（DXA），最常见的测试，以评估 骨健康，仅测量骨矿物质密度（BMD），无法提供骨质量信息; 因此，它低估了T1 D患者的骨折风险。因此，我们假设髋关节结构和 与对照组相比，绝经后T1 D妇女的骨组织材料质量将受到损害。 与总体假设一致，我们建议测定髋骨结构质量（vBMD，骨密度）， 几何形状和骨强度）使用定量计算机断层扫描（QCT）和一种新的计算机 基于图像的技术（有限元分析）[目的1]，并评价骨组织成分的差异 使用拉曼光谱、纳米压痕和 与年龄和BMI相比，绝经后T1 D女性的背散射电子显微镜检查[目的2] 无糖尿病的绝经后妇女。 随着护理的改善，T1 D患者的寿命更长，并且没有具体的预防方法， 治疗患有T1 D的老年人骨质疏松症。因此，这项研究将阐明可能的机制， 绝经后T1 D女性的骨脆性，长期目标是预防髋部骨折和相关 这一高风险人群的发病率。 拟议的K23奖将通过提供必要的支持，促进我向独立过渡; 1） 获得并巩固临床科学知识和转化研究技能; 2）培养专业 研究技能，3）发展独立研究的道路。为了实现我的职业目标，我 组建了一个导师团队，包括1）T1 D领域的专家Janet Snell-Bergeon博士，博士 并发症和流行病学，由美国国立卫生研究院资助了十多年;和2）温迪·柯尔特博士，博士， 他是骨代谢和衰老领域的资深科学家，三十多年来一直获得NIH的资助。在 此外，指导团队的专业知识（Chonchol博士，骨代谢领域的临床研究员， Drs.卡彭特和弗格森，生物力学工程师和派尔博士，生物统计学家）将有助于提高我的 在这个领域的职业生涯。拟议研究的结果将产生必要的数据，以提出R 01重点 降低T1 D患者骨质疏松风险的治疗策略。