DOES LIFESTYLE INTERVENTION IN OBESE OLDER ADULTS IMPROVE BONE QUALITY?

对肥胖老年人进行生活方式干预可以改善骨骼质量吗？

• 批准号: 10401749
• 负责人: DENNIS T. VILLAREAL
• 金额: $ 67.56万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10401749
• 关键词: Adipose tissue; Adult; Adverse effects; Affect; Age-Related Bone Loss; Ankle; Attenuated; Belief; Body Composition; Body Weight decreased; Body mass index; Bone Density; Center for Translational Science Activities; Climacteric; Clinical Practice Guideline; Cognition; Complication; Core Facility; Coupled; Data; Diet; Disease; Dual-Energy X-Ray Absorptiometry; Elderly; Exercise; Finite Element Analysis; Fracture; Habits; Health; Hip Fractures; Independent Living; Inflammation; Inflammatory; Intervention; Leg; Life; Life Style; Lifestyle Therapy; Measures; Mediating; Medical center; Medicine; Monitor; Muscle; Obesity; Older Population; Osteocytes; Osteogenesis; Pathway interactions; Peripheral; Physical Function; Population; Property; Public Health; Quality of life; Randomized; Randomized Controlled Trials; Resolution; Resources; Risk; Risk Factors; Safety; Scanning; Shapes; Societies; Spatial Distribution; Techniques; Testing; Therapeutic Intervention; Visceral; WNT Signaling Pathway; Weight-Bearing state; X-Ray Computed Tomography; bone; bone health; bone imaging; bone loss; bone quality; bone strength; cardiometabolic risk; college; cortical bone; evidence base; fracture risk; healthy lifestyle; high risk; hip bone; human old age (65+); improved; in vivo; inhibitor; lifestyle intervention; loss of function; novel; older men; older women; optimal treatments; preservation; response; satisfaction; substantia spongiosa; treatment strategy; weight maintenance

ABSTRACT Despite the serious public health problem of obesity in older adults, the appropriate treatment approach for obese older adults remains highly controversial. A prevailing safety concern is that weight loss could cause further loss of bone mineral density (BMD) and increase the risk of bone fractures. Indeed, recent studies have shown that lifestyle therapy (diet plus exercise) resulting in weight loss in this understudied population improves physical function, cardiometabolic risk factors, and cognition, but a major complication appears to be loss of BMD. The addition of exercise to diet-induced weight loss attenuated but did not eliminate weight-loss- induced reduction of BMD. Previous studies, however, used dual-energy-x-ray-absorptiometry to monitor bone changes, which provides information on bone quantity but not bone quality. Bone quality refers to the material and structural properties of bone strength. The load-bearing capacity of a bone depends not only on the amount of bone but also on the spatial distribution and intrinsic properties of the materials that comprise the bone. Because of previous lack of options to assess bone quality in vivo, there has been little or no scientific study of the possibility that lifestyle change in obese older adults improves bone quality. Preliminary studies suggest that lifestyle therapy may improve bone quality despite reducing BMD by suppressing inflammation. This will be the first randomized controlled trial (RCT) in obese older adults to comprehensively examine the effects of lifestyle therapy on bone quality using state-of-the-art and novel techniques. One- hundred-twenty obese older adults will be randomized to 1 year of lifestyle intervention or healthy lifestyle (control) to test the following primary hypotheses: 1) lifestyle therapy will improve bone microarchitecture in obese older adults relative to a control condition, 2) lifestyle therapy will improve femoral bone strength in obese older adults relative to a control condition, and 3) lifestyle therapy will improve bone material strength in obese older adults relative to a control condition. The secondary hypothesis is that changes in the canonical Wnt signaling (↓ sclerostin, an inhibitor of bone formation during states of unloading) and noncanonical Wnt signaling (↓ Wnt5A/Sfrp5 and inflammation) may mediate the changes in bone quality during lifestyle therapy. The central hypothesis is that lifestyle intervention will be highly successful in obese older adults with resultant improvement in the material and structural properties of bone (i.e. bone quality) despite a reduction in BMD. The track record of the investigative team in lifestyle interventions in obese older adults, coupled with the Bone Imaging Core Resources at the Center for Translational Research on Inflammatory Diseases at Baylor College of Medicine and Michael E DeBakey VA Medical Center, represents an unprecedented opportunity to prove the hypothesis that lifestyle therapy improves bone quality in this population. The evidence-based data from this RCT should resolve the lingering controversy of whether lifestyle intervention is safe for bone health and thus overall beneficial, which will change clinical practice guidelines for obesity in older adults.

抽象的 尽管老年人有严重的公共卫生问题，但适当的治疗方法 肥胖的老年人仍然存在极大的争议。一个普遍的安全问题是减肥可能导致 骨矿物质密度（BMD）的进一步丧失，并增加骨折的风险。确实，最近的研究已经 表明生活方式疗法（饮食加运动）导致这种知识的人群减肥 改善身体机能，心脏代谢危险因素和认知，但主要并发症似乎是 损失BMD。饮食诱发的减肥运动增加了运动，但并未消除减肥 - 诱导BMD降低。然而，先前的研究使用双能量-X射线 - 亚孔测定法来监测骨骼 变化，提供有关骨骼数量但骨质质量的信息。骨质质量是指材料 和骨强度的结构特性。骨骼的承重能力不仅取决于 骨骼的量，但还取决于完成材料的空间分布和内在特性 骨。由于以前缺乏评估体内骨质质量的选择，因此几乎没有科学 研究肥胖老年人生活方式改变的可能性可以改善骨质质量。初步研究 表明生活方式疗法可以通过抑制注射来改善减少BMD的骨质质量任务。 这将是肥胖老年人的第一个随机对照试验（RCT） 使用最先进的技术和新技术检查生活方式疗法对骨骼质量的影响。一- 一百二十名肥胖的老年人将被随机分为1年的生活方式干预或健康的生活方式 （对照）测试以下主要假设：1）生活方式疗法将改善骨微体系结构 肥胖的老年人相对于对照条件，2）生活方式疗法将改善股骨强度 肥胖的老年人相对于对照条件，3）生活方式疗法将改善骨料的强度 肥胖的老年人相对于对照条件。次要假设是规范的变化 Wnt信号传导（↓硬化蛋白，卸载状态下骨形成的抑制剂）和非规范Wnt 信号传导（↓WNT5A/SFRP5和炎症）可能会介导生活方式治疗期间骨骼质量的变化。 中心假设是生活方式干预将在肥胖的老年人中取得很大成功 最终改善了骨头（即骨质）目的地的材料和结构特性的降低 BMD。调查团队在肥胖老年人生活方式干预方面的往绩，再加上 贝勒炎症性疾病转化研究中心的骨骼成像核心资源 医学院和Michael E Debakey VA医疗中心，代表了前所未有的机会 证明生活方式疗法可以改善该人群的骨质质量的假设。基于证据的数据 从这个RCT中，应该解决生活方式干预是否安全骨骼健康的挥之不去的争议 因此，总体上有益，这将改变老年人肥胖症的临床实践指南。