DOES LIFESTYLE INTERVENTION IN OBESE OLDER ADULTS IMPROVE BONE QUALITY?

摘要 尽管老年人肥胖是严重的公共卫生问题，但适当的治疗方法 肥胖老年人仍然存在很大争议。普遍存在的安全问题是体重减轻可能会导致 骨矿物质密度（BMD）进一步损失并增加骨折的风险。事实上，最近的研究表明 研究表明，生活方式疗法（饮食加运动）可以使这一未被充分研究的人群减轻体重 改善身体功能、心脏代谢危险因素和认知，但一个主要并发症似乎是 BMD 损失。在饮食引起的减肥中加入运动会减弱但并不能消除减肥效果 导致 BMD 降低。然而，之前的研究使用双能 X 射线吸收测定法来监测骨骼 变化，它提供有关骨量的信息，但不提供骨质量的信息。骨质量是指材质 和骨强度的结构特性。骨骼的承载能力不仅取决于 骨量，还取决于构成骨的材料的空间分布和内在特性 骨头。由于以前缺乏评估体内骨质量的选择，因此很少或根本没有科学依据 研究肥胖老年人生活方式的改变是否可以改善骨质量。初步研究 表明生活方式疗法可以改善骨质量，尽管通过抑制炎症来降低骨密度。 这将是第一个针对肥胖老年人的随机对照试验（RCT），以全面评估 使用最先进的新技术检查生活方式疗法对骨质量的影响。一- 20 名肥胖老年人将被随机分配接受为期 1 年的生活方式干预或健康生活方式 （对照）测试以下主要假设：1）生活方式疗法将改善骨微结构 相对于对照条件的肥胖老年人，2）生活方式疗法将改善股骨强度 相对于对照条件的肥胖老年人，3）生活方式疗法将改善骨材料强度 相对于对照条件的肥胖老年人。第二个假设是规范的变化 Wnt 信号传导（↓ 硬化素，卸载状态下骨形成的抑制剂）和非经典 Wnt 信号传导（↓ Wnt5A/Sfrp5 和炎症）可能会在生活方式治疗期间介导骨质量的变化。 核心假设是，生活方式干预对于患有以下疾病的肥胖老年人将非常成功： 尽管骨量减少，但骨的材料和结构特性（即骨质量）得到改善 弹道导弹防御。调查小组在肥胖老年人生活方式干预方面的记录，以及 贝勒炎症性疾病转化研究中心的骨成像核心资源 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量这一假设。基于证据的数据 这项随机对照试验应能解决生活方式干预对骨骼健康是否安全这一挥之不去的争议 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.