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

摘要 绝经后患有1型糖尿病(T1D)的女性患髋部骨折的风险是女性的6到8倍 与没有糖尿病的女性相比。髋部骨折与严重的发病率、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。 与未患糖尿病的受试者相比。双X射线吸收测量法(DXA)，这是最常见的评估方法 骨健康，只测量面骨密度(BMD)，不提供有关骨质量的信息； 因此，它低估了T1D患者的骨折风险。因此，我们假设臀部结构和 与对照组相比，患有T1D的绝经后妇女的骨组织材料质量将受到影响。 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)和一种新型的计算机化 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 和使用拉曼光谱、纳米压痕和组织材料特性的组织材料特性 患有T1D的绝经后妇女与年龄和BMI的背散射电子显微镜[AIM 2] 与无糖尿病的绝经后女性相匹配。 随着护理的改善，患有T1D的人寿命更长，而且没有具体的预防和治疗方法 T1D治疗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T1D妇女的骨脆性及其预防髋部骨折和相关的长期目标 这一高危人群的发病率。 拟议的K23奖励将通过提供必要的支持来促进我向独立的过渡；1) 获取和巩固临床科学知识和翻译研究技能；2)培养专业人才 研究技能，以及3)发展一条独立研究的道路。为了实现我的职业目标，我有 组建了一个导师团队，成员包括T1D领域的专家珍妮特·斯内尔-贝金博士 并发症和流行病学，由美国国立卫生研究院资助十多年；以及2)温迪·科尔特博士，博士， 他是骨代谢和衰老领域的资深科学家，拥有超过30年的NIH持续资助。在……里面 此外，指导团队的专业知识(骨代谢领域的临床研究员Chonchol博士， 生物力学工程师卡彭特博士和弗格森博士以及生物统计学家派尔博士)将帮助推进我的 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，以提出以R01为重点的 关于降低T1D骨质疏松风险的治疗策略。

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.