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.

项目摘要尽管肥胖症的不良代谢和功能后果，但饮食减肥（WL）建议由于WL相关的骨矿物质密度（BMD）和骨质疏松骨折的风险增加。几项研究表明，运动对体重的BMD的积极作用 - 稳定的老年人；但是，研究锻炼在饮食中保留骨骼的能力的文献是令人惊讶的等效。不一致的发现可能是由于不同的锻炼处方所致我们的小组提出了渐进抵抗训练（RT）的卓越能力，以最大程度地减少骨质流失与有氧训练相比，饮食WL。然而，RT仍会发生一些骨质流失，促使考虑替代或调整骨保护策略。药物疗法代表另一种对策策略和几种药物是FDA批准的，以预防和治疗骨质疏松症。尤其是双膦酸盐是一种有望的选择，因为它们可以减少骨骼分辨率（已更新在WL期间），并且似乎也钝化了急性运动对骨骼的分解代谢作用，从而发出了信号 WL期间的添加效应的潜力 - 尽管这些假设尚未正式检验。解决这些知识差距，拟议的12个月，2x2阶乘随机对照试验将比较 RT加骨负荷运动和双膦酸盐对饮食WL的独立和联合效果 392岁（60岁以上）肥胖的成年人（BMI = 30-40 kg/m2）的相关骨质流失，他们也处于危险之中对于低BMD（总臀部T-SCORE：0至-2.2）和科罗拉多大学 - 阿斯丘茨大学医疗校园。所有参与者都将接受相同的组介导的饮食WL干预，并且是随机分为四组之一：无RT和安慰剂胶囊（Nort+PL）；渐进的RT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70 mg口服 alendronate; Nort+bis）;或进行性RT加骨骼加载练习和双膦酸盐胶囊（RT ++ bis）。由于饮食中的WL和临床实用性在预测骨折后发生了牢固的变化，我们的主要结果是通过双重X射线绝对持续图（DXA）测得的总髋部ABMD的变化。这将是由DXA评估在其他骨骼部位完成，以及高分辨率的外围定量计算机断层扫描（HR-PQCT）衍生的隔室体积（V）BMD，小梁骨微体系结构，皮质厚度/孔隙度以及盘状半径和胫骨的强度 - 允许评估干预效果对新型骨质质量措施的评估。最后，评估骨骼更新和代谢的生物标志物将洞悉RT+和BIS在骨骼上的作用饮食中的重塑单元。