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

运动和双磷酸盐的使用可最大限度地减少老年人与体重减轻相关的骨质流失

• 批准号: 10517723
• 负责人: Daniel P Beavers
• 金额: $ 138.53万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10517723
• 关键词: Acute; Address; Adjuvant; Aerobic; Affect; Alendronate; Biological Markers; Body Weight decreased; Body mass index; Bone Density; Bone Resorption; Bone remodeling; Clinical; Clinical Research; Colorado; Complement; Data; Data Analytics; Distal; Effectiveness of Interventions; Elderly; Exercise; FDA approved; Fracture; Hip region structure; Intervention; Knowledge; Literature; Measures; Mechanics; Mediating; Medical; Metabolic; Obesity; Operative Surgical Procedures; Oral; Osteoclasts; Osteoporosis; Outcome; Participant; Pathway interactions; Peripheral; Pharmaceutical Preparations; Pharmacotherapy; Placebos; Population; Porosity; Radial; Randomized; Randomized Controlled Trials; Recommendation; Resolution; Risk; Roentgen Rays; Role; Safety; Secondary to; Signal Transduction; Site; Suggestion; Testing; Thick; Training; Treatment Efficacy; Universities; Weight; X-Ray Computed Tomography; adult obesity; base; bisphosphonate; bone; bone loss; bone mass; bone metabolism; bone preservation; bone quality; bone turnover; capsule; dietary; exercise intensity; exercise prescription; forest; fracture risk; insight; novel; obesity treatment; osteoporosis with pathological fracture; post intervention; preservation; prevent; primary outcome; skeletal; strength training; substantia spongiosa; tibia; treatment effect; treatment guidelines; treatment response; weight loss intervention

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.

项目总结 尽管肥胖会对新陈代谢和功能产生不利影响，但饮食减肥(WL)建议 对于老年人来说，由于WL相关的骨密度(BMD)和 增加骨质疏松性骨折的风险。几项研究表明，锻炼对体重中的骨密度有积极影响。 稳定的老年人；然而，研究在饮食中锻炼保存骨骼的能力的文献是 出人意料的模棱两可。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 我们小组建议进行渐进阻力训练(RT)以最大限度地减少骨丢失 饮食WL，与有氧训练相比。尽管如此，RT仍会发生一些骨丢失，促使 考虑替代或辅助的骨保护策略。药物疗法代表着另一种 对策策略，几种药物被FDA批准用于预防和治疗骨质疏松症。 尤其是，双膦酸盐是一个很有希望的选择，因为它们减少了骨吸收(骨吸收被上调 在WL期间)，而且似乎也削弱了急性运动对骨骼的分解代谢效应，从而发出信号 WL过程中潜在的加性效应--尽管这些假说尚未经过正式检验。致信地址 这些知识差距，建议的12个月、2x2析因随机对照试验将比较 RT加骨负荷运动和双膦酸盐应用对膳食WL的单独和联合影响 392名患有肥胖(BMI=30-40公斤/平方米)的老年(60岁以上)成年人的相关骨丢失也处于危险之中 在维克森林大学和科罗拉多大学安舒茨分校的低BMD(髋关节总T分：0到-2.2) 医学院。所有参与者都将接受相同的小组中介饮食WL干预，并将 随机分为四组：不放疗+安慰剂胶囊(Nort+PL)；渐进放疗+骨负荷 运动和安慰剂胶囊(RT++PL)；不使用RT和双磷酸盐胶囊(每周口服70 mg 阿伦磷酸钠；Nort+BIS)；或渐进RT加骨负荷运动和双磷酸盐胶囊 (RT++BIS)。由于它在饮食WL后的强劲变化和在预测骨折方面的临床实用价值，我们的主要 结果是通过双X射线骨密度仪(DXA)测量的全髋骨密度的变化。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)得出的间室体积(V)骨密度、骨小梁 微结构、皮质厚度/孔隙度以及桡骨远端和胫骨的强度--允许 骨质量新指标干预效果的评估。最后，对 骨转换和代谢的生物标志物将提供对RT+和BIS在骨中的作用的深入了解 饮食WL期间的重塑单位。