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.

项目概要 尽管肥胖会产生不利的代谢和功能后果，但饮食减肥（WL）建议 由于 WL 会导致骨密度 (BMD) 降低，因此对于老年人来说仍然存在争议 骨质疏松性骨折的风险增加。多项研究表明，运动对体重方面的骨密度有积极影响 稳定的老年人；然而，研究饮食 WL 期间运动保护骨骼能力的文献是 令人惊讶的是模棱两可。不一致的结果可能是由于不同的运动处方造成的，最近的数据来自 我们的小组表明，渐进式抗阻训练（RT）具有卓越的能力，可以最大限度地减少骨质流失 饮食 WL 与有氧训练相比。然而，放疗期间仍然会发生一些骨质流失，这促使 考虑替代或辅助骨保护策略。药物治疗代表另一种 对策策略，FDA 批准了多种药物来预防和治疗骨质疏松症。 特别是双膦酸盐是一个有前途的选择，因为它们可以减少骨吸收（骨吸收上调） WL 期间），并且似乎还能减弱急性运动对骨骼的分解代谢作用，从而发出信号 WL 期间潜在的附加效应——尽管这些假设尚未经过正式测试。致地址 针对这些知识差距，拟议的 12 个月、2x2 析因随机对照试验将比较 RT 加骨负荷运动和双磷酸盐使用对饮食 WL 的独立和综合影响 392 名患有肥胖症 (BMI=30-40 kg/m2) 的老年人（60 岁以上）存在相关骨质流失，他们也面临风险 维克森林大学和科罗拉多大学安舒茨分校的低 BMD（总髋部 T 值：0 至 -2.2） 医学校区。所有参与者都将接受相同的团体介导的饮食 WL 干预，并 随机分为四组之一：无 RT 和安慰剂胶囊 (NoRT+PL)；渐进性放疗加骨负荷 练习和安慰剂胶囊 (RT++PL)；无 RT 和双膦酸盐胶囊（每周口服 70 毫克） 阿仑膦酸钠；诺RT+BIS）；或渐进性放疗加骨负荷练习和双膦酸盐胶囊 (RT++BIS)。由于其随膳食 WL 的剧烈变化以及预测骨折的临床实用性，我们的主要 结果是通过双 X 射线吸收仪 (DXA) 测量的总髋部 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) 衍生的房室体积 (v)BMD、骨小梁 微结构、皮质厚度/孔隙率以及远端桡骨和胫骨的强度 - 允许 评估骨质量新指标的干预效果。最后，评估 骨转换和代谢的生物标志物将有助于深入了解 RT+ 和 BIS 对骨的作用 饮食WL期间的重塑单位。