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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

基本信息

批准号：
10376142
负责人：
Viral N Shah
金额：
$ 16.69万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-10 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10376142
关键词：
3-Dimensional Address Adult Affect Age Animal Model Biopsy Biopsy Specimen Body mass index Bone Density Bone Tissue 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 Persons Population Postmenopause Prevention approach Property Raman Spectrum Analysis Reporting Research Research Personnel Research Technics Risk Roentgen Rays Senior Scientist Site 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

项目摘要

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.

抽象的患有 1 型糖尿病 (T1D) 的绝经后女性髋部骨折的风险高出六到八倍与没有糖尿病的女性相比。髋部骨折与显着的发病率、死亡率、丧失能力有关。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没有糖尿病的受试者相比。双 X 射线吸收测定法 (DXA)，最常见的评估测试骨骼健康，仅测量面骨矿物质密度（BMD），无法提供骨质量信息；因此，它低估了 1 型糖尿病患者的骨折风险。因此，我们假设髋关节结构和与对照组相比，患有 T1D 的绝经后女性的骨组织材料质量会受到影响。与总体假设一致，我们建议确定髋骨结构质量（vBMD、骨几何形状和骨强度）使用定量计算机断层扫描（QCT）和一种新颖的计算机化基于图像的技术（有限元分析）[目标 1]，并评估骨组织成分的差异使用拉曼光谱、纳米压痕和经髂骨活检获得的组织材料特性与年龄和体重指数相比，绝经后 T1D 女性的背散射电子显微镜检查[目标 2] 匹配没有糖尿病的绝经后妇女。随着护理的改善，T1D 患者的寿命更长，并且没有具体的预防和治疗方法治疗老年 T1D 骨质疏松症。因此，本研究将阐明其可能的机制患有 T1D 的绝经后妇女的骨脆性，长期目标是预防髋部骨折及相关疾病这一高危人群的发病率。拟议的 K23 奖项将通过提供必要的支持来促进我向独立的过渡； 1）获取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) 开辟独立研究之路。为了实现我的职业目标，我组建了一个导师团队，其中包括 1) Janet Snell-Bergeon 博士，T1D 领域的专家并发症和流行病学，由 NIH 资助十多年； 2) Wendy Kohrt 博士，博士，骨代谢和衰老领域的资深科学家，三十多年来持续获得 NIH 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，博士。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）将帮助推进我的研究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，以提出以 R01 为重点的研究降低 T1D 骨质疏松风险的治疗策略。