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

基本信息

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
项目类别：
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

项目摘要

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，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然而，与有氧训练相比，饮食 WL 仍然会发生一些骨质流失，从而导致骨质流失。考虑替代或辅助骨保护策略是另一种方法。对策策略，FDA 批准了多种药物来预防和治疗骨质疏松症。特别是双磷酸盐，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。对于这些知识差距，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）医学校园。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)；锻炼和安慰剂胶囊 (RT++PL)；无 RT 和双膦酸盐胶囊（每周口服 70 毫克）阿仑膦酸钠；NoRT+BIS）；或渐进性 RT 加骨负荷练习和双膦酸盐胶囊 (RT++BIS) 由于其在饮食 WL 后的强劲变化以及预测骨折的临床实用性，我们的主要研究结果是通过双 X 射线吸收测定法 (DXA) 测量的总髋部 aBMD 的变化。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。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。