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， 肥胖的老年人仍然备受争议。一个普遍的安全问题是，体重减轻可能会导致 骨矿物质密度（BMD）进一步降低，并增加骨折的风险。事实上，最近的研究 表明生活方式疗法（饮食加运动）导致这一研究不足的人群体重减轻， 改善身体功能、心脏代谢危险因素和认知，但主要并发症似乎是 BMD的损失。在饮食引起的体重减轻中加入运动会减弱但不能消除体重减轻- 导致BMD降低。然而，以前的研究使用双能X射线吸收法来监测骨 变化，其提供关于骨量而不是骨质量的信息。骨质是指材料 和骨骼强度的结构特性。骨骼的承重能力不仅取决于 骨的量，而且还取决于构成骨的材料的空间分布和固有特性。 骨头由于以前缺乏在体内评估骨质量的方法， 研究肥胖老年人生活方式改变改善骨质的可能性。初步研究 提示尽管通过抑制炎症降低了BMD，但生活方式疗法可以改善骨质量。 这将是第一个在肥胖老年人中进行的随机对照试验（RCT）， 使用最先进的新技术检查生活方式疗法对骨质量的影响。第一 120名肥胖老年人将被随机分配到1年的生活方式干预组或健康生活方式组 （对照）以检验以下主要假设：1）生活方式治疗将改善骨微结构， 肥胖老年人相对于对照条件，2）生活方式治疗将改善股骨骨强度， 肥胖老年人相对于对照条件，和3）生活方式治疗将改善骨材料强度， 肥胖的老年人相对于对照条件。第二个假设是， Wnt信号传导（↓ sclerostin，一种在卸载状态下骨形成的抑制剂）和非经典Wnt 信号传导（↓ Wnt 5A/Sfrp 5和炎症）可能介导生活方式治疗期间骨质量的变化。 中心假设是，生活方式干预将是非常成功的肥胖老年人， 尽管骨的材料和结构特性（即骨质量）降低， BMD。调查小组在肥胖老年人生活方式干预方面的记录， 贝勒大学炎症性疾病转化研究中心的骨成像核心资源 医学院和迈克尔E DeBakey VA医疗中心，代表了一个前所未有的机会， 证明生活方式疗法改善这一人群骨质量的假设。循证数据 这项随机对照试验的结果应该可以解决生活方式干预对骨骼健康是否安全的争论 因此总体上是有益的，这将改变老年人肥胖症的临床实践指南。

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.