DOES LIFESTYLE INTERVENTION IN OBESE OLDER ADULTS IMPROVE BONE QUALITY?

摘要 尽管老年人肥胖是一个严重的公共卫生问题，但适当的治疗方法 肥胖的老年人仍然备受争议。一个普遍的安全问题是，减肥可能会导致 进一步丢失骨密度(BMD)并增加骨折的风险。事实上，最近的研究已经 表明生活方式疗法(饮食加运动)在这一未被研究的人群中导致体重减轻 改善身体功能、心脏代谢危险因素和认知，但一个主要的并发症似乎是 骨密度丢失。在饮食诱导的减肥中加入运动会减弱但不会消除减肥-- 诱导骨密度降低。然而，先前的研究使用双能量x射线吸收测量法来监测骨骼。 更改，它提供有关骨骼数量的信息，但不提供骨骼质量信息。骨质量指的是材料 以及骨强度的结构特性。骨骼的承载能力不仅取决于 不仅取决于骨的数量，而且还取决于组成骨的材料的空间分布和固有特性 骨头。由于之前缺乏评估活体骨骼质量的选择，几乎没有或根本没有科学的 研究肥胖老年人改变生活方式改善骨骼质量的可能性。初步研究 提示生活方式疗法可能会改善骨质量，尽管通过抑制炎症来降低骨密度。 这将是首个针对肥胖老年人的随机对照试验 使用最先进和新颖的技术检查生活方式疗法对骨骼质量的影响。一是- 120名肥胖的老年人将随机接受为期一年的生活方式干预或健康生活方式 (对照)检验以下主要假设：1)生活方式疗法将改善骨微结构 肥胖老年人相对于对照组，2)生活方式治疗将改善股骨强度 与对照条件相比，肥胖的老年人和3)生活方式治疗将改善骨材料强度 相对于对照条件，肥胖的老年人。第二个假设是，规范中的变化 WNT信号(↓硬化素，一种卸载状态下的骨形成抑制物)与非典范WNT 信号转导(↓、WNT5A/SFRP5和炎症)可能参与生活方式治疗过程中骨质量的改变。 中心假设是，生活方式干预在患有肥胖的老年人中将非常成功 骨的材料和结构特性(即骨质量)的结果改善，尽管 骨密度。调查小组在对肥胖老年人进行生活方式干预方面的记录，加上 贝勒炎症性疾病翻译研究中心的骨成像核心资源 医学院和迈克尔·E·德巴基退伍军人医学中心，代表着前所未有的机会 证明生活方式疗法改善这一人群骨骼质量的假设。基于证据的数据 因此，RCT应该能解决生活方式干预对骨骼健康是否安全的挥之不去的争议 因此总体上是有益的，这将改变老年人肥胖的临床实践指南。

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.