Exercise and Bisphosphonate Use to Minimize Weight Loss Associated Bone Loss among Older Adults

项目摘要 尽管肥胖会导致不良的代谢和功能后果，但饮食减肥（WL）建议 由于WL相关的骨矿物质密度（BMD）降低， 会增加骨质疏松性骨折的风险几项研究表明，运动对体重中的BMD有积极影响- 稳定的老年人;然而，研究饮食WL期间运动保护骨的能力的文献， 令人惊讶的模棱两可。不一致的发现可能是由于不同的运动处方，最近的数据来自 我们的研究组提示渐进式抗阻训练（RT）在减少骨丢失方面具有优越的上级能力， 饮食WL，与有氧训练相比。尽管如此，RT仍会发生一些骨丢失，这促使了 考虑替代或辅助骨保护策略。药物治疗是另一种 因此，骨质疏松症的预防和治疗是一个非常重要的问题。 特别是双膦酸盐，是一种有希望的选择，因为它们减少骨吸收（骨吸收被上调）， 在WL期间），并且似乎也减弱了急性运动对骨骼的分解代谢作用，从而发出信号， 在WL过程中可能存在累加效应-尽管这些假设尚未得到正式验证。解决 由于这些知识差距，拟议的12个月2x2析因随机对照试验将比较 RT加骨负荷运动和使用双磷酸盐对膳食WL的独立和联合作用 在392名老年（60岁以上）肥胖（BMI=30-40 kg/m2）成人中， 维克森林大学和科罗拉多大学安舒茨分校的低BMD（全髋关节T评分：0至-2.2） 医学院。所有参与者将接受相同的组介导的饮食WL干预， 随机分为四组：无RT和安慰剂胶囊（NoRT+PL）;进行性RT加骨负荷 运动和安慰剂胶囊（RT++PL）;无RT和双膦酸盐胶囊（70 mg，每周口服 阿仑膦酸钠; NoRT+BIS）;或渐进性RT加骨负荷运动和双膦酸盐胶囊 (RT++BIS）。由于其在饮食WL后的强劲变化和在预测骨折方面的临床实用性，我们的主要研究结果是： 结果是通过双能X线吸收测定法（DXA）测量的全髋aBMD的变化。这将是 辅以其他骨骼部位的DXA评估，以及高分辨率外周定量 计算机断层扫描（HR-pQCT）衍生的房室容积（v）BMD，松质骨 桡骨远端和胫骨的微结构、皮质厚度/孔隙度和强度-允许 评估新骨质量指标的干预效果。最后，评估 骨转换和代谢的生物标志物将提供RT+和BIS对骨的作用的洞察 在饮食WL期间重塑单位。

PROJECT SUMMARY Despite adverse metabolic and functional consequences of obesity, dietary weight loss (WL) recommendation remains controversial for older adults due to WL associated reduction in bone mineral density (BMD) and increased risk of osteoporotic fracture. Several studies show a positive effect of exercise on BMD in weight- stable, older adults; however, literature examining the ability of exercise to preserve bone during dietary WL is surprisingly equivocal. Discordant findings may be due to varying exercise prescriptions, with recent data from our group suggestive of a superior ability of progressive resistance training (RT) to minimize bone loss during dietary WL, as compared to aerobic training. Nevertheless, some bone loss still occurs with RT, prompting the consideration of alternate or adjuvant osteoprotective strategies. Pharmacotherapy represents another countermeasure strategy, and several medications are FDA-approved to prevent and treat osteoporosis. Bisphosphonates, in particular, are a promising choice as they decrease bone resorption (which is upregulated during WL) and also appear to blunt the catabolic effect of acute exercise on bone, thereby signaling the potential for additive effects during WL — though these hypotheses have not been formally tested. To address these knowledge gaps, the proposed 12 month, 2x2 factorial randomized controlled trial will compare the independent and combined effects of RT plus bone loading exercise and bisphosphonate use on dietary WL associated bone loss among 392 older (60+ years) adults with obesity (BMI=30-40 kg/m2) who are also at risk for low BMD (total hip T-score: 0 to -2.2) at Wake Forest University and The University of Colorado-Anschutz Medical Campus. All participants will receive the same group-mediated dietary WL intervention and be randomized to one of four groups: no RT and placebo capsules (NoRT+PL); progressive RT plus bone-loading exercises and placebo capsules (RT++PL); no RT and bisphosphonate capsules (70 mg weekly oral alendronate; NoRT+BIS); or progressive RT plus bone-loading exercises and bisphosphonate capsules (RT++BIS). Due to its robust change following dietary WL and clinical utility in predicting fracture, our primary outcome is change in total hip aBMD measured via dual x-ray absorptiometry (DXA). This will be complemented by DXA assessment at other skeletal sites, as well as high resolution peripheral quantitative computed tomography (HR-pQCT) derived compartmental volumetric (v)BMD, trabecular bone microarchitecture, cortical thickness/porosity, and strength at the distal radius and tibia — allowing for assessment of intervention effectiveness on novel measures of bone quality. Finally, assessment of biomarkers of bone turnover and metabolism will provide insight into the roles of RT+ and BIS on the bone remodeling unit during dietary WL.