Effect of protein supplementation during weight loss on older adult bone health

项目摘要。韦弗博士寻求这个K25指导培训奖，以扩大她的生物工程研究 背景是创伤的医学成像和有限元建模， 研究生涯的重点是减少老年人的骨质疏松症和骨折。减肥会增加 老年人骨质流失和骨折的风险。这项拟议中的研究将检验总体假设，即 在体重减轻期间和之后的膳食蛋白质摄入将减轻患有肥胖症的老年人的骨丢失。指导 由一个在衰老、临床试验、骨代谢、 营养学和放射学，PI将：（1）发展老年学和老年医学的知识，（2）获得 临床试验设计和执行方面的培训，3）深入了解骨代谢， 结构，包括营养和减肥的影响，以及4）发展双能量计算的专业知识 断层扫描（CT）采集和后处理，以测量体积骨矿物质密度，皮质厚度， 和骨髓脂肪组织。韦弗博士的培训和研究将在维克森林学校进行。 医学在老龄化临床研究和特殊的放射学基础设施方面有着悠久的历史。的 与她在罗格斯大学营养科学系的共同导师的伙伴关系将提供额外的 与骨代谢的营养调节相关的资源和专业知识。拟议的辅助研究 正在进行的临床试验，UPLIFT：在减肥过程中利用蛋白质影响身体功能，将 检查骨骼健康超过6个月的积极减肥，然后是12个月的体重维持。 肌肉骨骼表型将在肥胖的老年人中进行比较，这些老年人随机分为：（1）较低的 用于减肥和随访的蛋白质饮食，（2）仅用于减肥的高蛋白质饮食，或（3）高蛋白质饮食 进行减肥和随访。辅助研究通过增加以下双能量CT扫描扩展了UPLIFT试验： 在基线、6个月和18个月时对腰椎和股骨近端进行比较， 与较低的蛋白质摄入量相比：椎骨和股骨小梁体积骨密度和皮质骨密度 厚度（主要目的），骨髓脂肪过多，可能改变骨小梁基质并影响骨强度 （次要目的1），以及使用受试者特定有限元建模预测的骨强度和骨折风险 （第二目标）。这项研究将测试在主动减肥过程中，高蛋白饮食是否会改善骨骼的结果 （在6个月时评估），如果在体重维持期间保持较高的蛋白质摄入量， 骨（18个月时评价）。拟议中的培训和研究计划将启动韦弗博士的职业生涯， 独立研究员专注于应用生物工程技术：1）开发翻译工具， 骨折预测，和2）在临床试验中评估骨保护干预-最终导致改善 预防骨质疏松症和骨折的诊断、预后工具、临床建议和治疗 在老年人中。

Project Summary. Dr. Weaver seeks this K25 mentored training award to expand her bioengineering research background in medical imaging and finite element modeling of trauma towards pursuit of an independent research career focused on reducing osteoporosis and fracture in older adults. Weight loss poses an increased risk of bone loss and fracture in older adults. The proposed research will test the overall hypothesis that higher dietary protein intake during and following weight loss will attenuate bone loss in older adults with obesity. Guided by an accomplished multidisciplinary mentoring team with expertise in aging, clinical trials, bone metabolism, nutrition, and radiology, the PI will: (1) Develop knowledge of gerontology and geriatric medicine, (2) Acquire training in the design and execution of clinical trials, 3) Obtain in-depth knowledge on bone metabolism and structure, including the influence of nutrition and weight loss, and 4) Develop expertise in dual-energy computed tomography (CT) acquisition and post-processing to measure volumetric bone mineral density, cortical thickness, and bone marrow adipose tissue. Dr. Weaver's training and research will take place at Wake Forest School of Medicine which has a strong history of clinical research in aging and an exceptional radiology infrastructure. The partnership with her co-mentor at Rutgers within the Department of Nutritional Sciences will provide additional resources and expertise related to the nutritional regulation of bone metabolism. The proposed ancillary study to the ongoing clinical trial, UPLIFT: Utilizing Protein During Weight Loss to Impact Physical Function, will examine bone health over 6 months of active weight loss, followed by 12 months of weight maintenance. Musculoskeletal phenotypes will be compared in older adults with obesity randomized to either: (1) a lower protein diet for weight loss and follow-up, (2) a higher protein diet for weight loss only, or (3) a higher protein diet for weight loss and follow-up. The ancillary study expands the UPLIFT trial by adding dual-energy CT scans of the lumbar spine and proximal femur at baseline, 6 months, and 18 months to compare the influence of a higher versus lower protein intake on: vertebral and femoral trabecular volumetric bone mineral density and cortical thickness (Primary Aim), bone marrow adiposity which may alter the trabecular matrix and affect bone strength (Secondary Aim 1), and bone strength and fracture risk predicted with subject-specific finite element modeling (Secondary Aim 2). The study will test if a higher protein diet improves bone outcomes during active weight loss (evaluated at 6 months), and if maintaining higher protein intake during weight maintenance further preserves bone (evaluated at 18 months). The proposed training and research plan will launch Dr. Weaver's career as an independent investigator focused on applying bioengineering techniques to: 1) develop translational tools for fracture prediction, and 2) assess osteoprotective interventions in clinical trials—ultimately leading to improved diagnostics, prognostic tools, clinical recommendations, and therapies for preventing osteoporosis and fracture in older adults.