Biomechanical mechanisms underlying skeletal fragility in older adults with Type 1 diabetes

患有 1 型糖尿病的老年人骨骼脆弱的生物力学机制

• 批准号: 10012242
• 负责人: MARY L BOUXSEIN
• 金额: $ 31.3万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-12 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10012242
• 关键词: 3-Dimensional; Address; Adult; Advanced Glycosylation End Products; Age; Aging; Architecture; Area; Autopsy; Biomechanics; Bone Density; Bone Matrix; Bone structure; Clinical; Complication; Complications of Diabetes Mellitus; Cross-Sectional Studies; Data; Development; Diabetes Mellitus; Diagnosis; Disease; Dual-Energy X-Ray Absorptiometry; Elderly; Femur; Finite Element Analysis; Fourier Transform; Fracture; Glucose; Goals; Health; Hip Fractures; Hip region structure; Image; Incidence; Individual; Inferior; Insulin-Dependent Diabetes Mellitus; Knowledge; Lead; Life Expectancy; Longevity; Methods; Microvascular Dysfunction; Nature; Neck; Operative Surgical Procedures; Osteoporosis; Outcome; Patients; Periodicity; Postmenopause; Property; Risk; Serum; Skin; Specimen; Structure; Tissues; Vulnerable Populations; Woman; X-Ray Computed Tomography; base; bone; bone fragility; bone mass; bone quality; bone strength; clinical care; cohort; cortical bone; diabetic; experience; fracture risk; glucose monitor; glycemic control; high risk; improved; in vivo; insight; men; non-diabetic; novel; pentosidine; prevent; repaired; skeletal; substantia spongiosa

PROJECT SUMMARY / ABSTRACT As advances in clinical care continue to improve the lifespan of adults with type 1 diabetes (T1D), these patients have experienced an increase in aging-related diseases, including osteoporosis. As compared to nondiabetic adults, patients with T1D have an increased risk of fractures, particularly at the hip. This clinically important problem is further compounded by the fact that patients with T1D experience poorer outcomes following a fracture. However, little is currently known about the effect of T1D on bone composition and bone quality, particularly in older adults. In this proposal, our goal is to investigate biomechanical mechanisms of skeletal fragility in postmenopausal women and men age > or = to 50 years with T1D. We will compare tissue level bone biomechanical properties and bone composition using ex vivo femoral specimens from adults with longstanding T1D (50+ year duration) and matched nondiabetic controls, as well as from adults with and without T1D who are undergoing surgical repair of hip fracture. Using state-of-the-art methods, successful completion of our proposed aims will provide novel insights about the alterations in bone structure and quality that contribute to skeletal fragility in older adults with T1D, in whom fracture risk is highest. In addition, our findings will clarify the impact of diabetic history and accumulation of advanced glycation end-products on skeletal fragility in T1D. Addressing these critical gaps in knowledge will ultimately allow clinicians to develop rational approaches to prevent fractures in patients with T1D.

项目总结/摘要 随着临床护理的进步不断提高1型糖尿病（T1 D）成人的寿命，这些患者经历了与衰老相关的疾病，包括骨质疏松症的增加。 与非糖尿病成人相比，T1 D患者骨折的风险增加，特别是在髋关节。 这一临床上重要的问题由于T1 D患者在骨折后经历较差的结果而进一步复杂化。 然而，目前对T1 D对骨组成和骨质量的影响知之甚少，特别是在老年人中。 在这个建议中，我们的目标是调查绝经后女性和年龄≥ 50岁的T1 D男性骨骼脆弱性的生物力学机制。 我们将比较组织水平的骨生物力学性能和骨成分使用离体股骨标本从成人长期T1 D（50年以上的持续时间）和匹配的非糖尿病对照，以及从成人T1 D和没有T1 D谁正在接受髋关节骨折手术修复。 使用最先进的方法，成功完成我们提出的目标将提供有关骨结构和质量变化的新见解，这些变化导致T1 D老年人的骨骼脆弱性，其中骨折风险最高。此外，我们的研究结果将阐明糖尿病史和晚期糖基化终产物积累对T1 D骨骼脆性的影响。 解决这些关键的知识差距将最终使临床医生能够制定合理的方法来预防T1 D患者的骨折。