Incorporating Nutrition, Vests, Education, and Strength Training in Bone Health (INVEST in Bone Health)

项目总结 老年和肥胖是发病率和死亡率的普遍危险因素。减肥(WL)可以改善许多 肥胖的临床后果；然而，尽管它有好处，但建议对老年人进行有意的WL 仍然存在争议。不情愿，至少部分原因是已知的伴随全身而来的骨量丢失 WL和加剧与年龄有关的骨质疏松症和骨折风险的可能性。增加阻力 运动训练(RT-WL)是减弱但不能阻止WL相关的骨质减少的有效手段 矿物质密度(BMD)；然而，传统的RT干预对长期可行性构成障碍(即， 昂贵的设备、现场参与、训练有素的工作人员进行安全监督以及合规性下降)。 或者，通过外部替换减轻的体重来治疗与WL相关的机械应力的降低可能 还可以保持骨量。来自我们机构的试点数据表明，加权背心使用(旨在模仿 体重稳定性)在减少与WL相关的髋部骨密度损失方面是可行的且可能有效的，而 增加骨形成的生物标志物。如果得到确认，则可用性更高、管理更容易，并且 与RT相比，使用加权背心来抵消WL相关骨丢失的成本降低，保持显著 公共卫生潜力作为一种可翻译的战略，以最大限度地提高WL的心脏代谢益处，同时 将对肌肉骨骼系统的负面影响降至最低。拟议的R01研究的主要目标是 比较WL单独使用和与加权背心使用或RT一起使用对几个骨健康指标和 随后的骨折风险。我们建议对192名患有肥胖症(BMI=30-79岁)的老年人进行为期12个月的试验。 40 kg/m2)被随机分为三种干预措施之一(n=/组)：仅WL(WL；热量限制靶向 10%WL和遵循国家肥胖治疗指南)；WL+加权背心使用(WL+马甲；≥6 小时/天，体重替代滴定高达10%WL)；或WL+结构化RT(WL+RT；每周3天，10 练习，10-12次重复)。我们的主要研究结果是总髋关节小梁体积在12个月内的变化 BMD(VBMD)，我们假设，尽管总体重有类似的下降：(1) WL+VEST组全髋骨小梁vBMD较WL组减少，(2)全髋部丢失 与WL+RT相比，WL+VEST组的骨小梁vBMD不会增加。由一位才华横溢的新调查员领导，这 提案是在PI当前的MRSDA(K01 AG047291)期间完成的工作的自然延伸，以及 通过测试旨在优化老年人意向性WL的可翻译策略，对公共健康产生影响 与肥胖有关，同时阐明肌肉骨骼对WL反应的机制。

PROJECT SUMMARY Old age and obesity are prevalent risk factors for morbidity and mortality. Weight loss (WL) ameliorates many clinical consequences of obesity; yet despite its benefits, recommendation of intentional WL in older adults remains controversial. Reluctance stems, at least in part, from loss of bone mass known to accompany overall WL and the potential for exacerbation of age-related risk of osteoporosis and fracture. Addition of resistance exercise training (RT) to WL is an effective means to attenuate, but not stop, WL-associated reductions in bone mineral density (BMD); however, conventional RT interventions present barriers to long term feasibility (i.e., expensive equipment, on-site participation, safety supervision by trained staff, and waning compliance). Alternately, treating the WL-associated decrease in mechanical stress by replacing lost weight externally may also preserve bone mass. Pilot data from our institution signal that weighted vest use (designed to mimic weight stability) during WL is both feasible and likely efficacious in reducing WL-associated hip BMD loss while increasing biomarkers of bone formation. If confirmed, the greater availability, ease of administration, and reduced cost of weighted vest use to offset WL-associated bone loss, as compared to RT, holds significant public health potential as a translatable strategy to maximize the cardiometabolic benefits of WL, while minimizing negative implications for the musculoskeletal system. The main goal of the proposed R01 study is to compare the effects of WL alone and with weighted vest use or RT on several indicators of bone health and subsequent fracture risk. We propose a 12 month trial in 192 older (65-79 years) adults with obesity (BMI=30- 40 kg/m2) randomized to one of three interventions (n=64/group): WL alone (WL; caloric restriction targeting 10% WL and following national obesity treatment guidelines); WL plus weighted vest use (WL+VEST; ≥6 hours/day, weight replacement titrated up to 10% WL); or, WL plus structured RT (WL+RT; 3 days/week, 10 exercises, 10-12 repetitions). Our primary study outcome is 12 month change in total hip trabecular volumetric BMD (vBMD) and we hypothesize that despite similar reductions in total body weight: (1) participants in the WL+VEST group will show attenuated losses of total hip trabecular vBMD versus WL, and (2) loss in total hip trabecular vBMD will be no greater in WL+VEST compared to WL+RT. Led by a talented New Investigator, this proposal is a natural extension of the work accomplished during the PI’s current MRSDA (K01 AG047291), and confers public health impact by testing a translatable strategy aimed at optimizing intentional WL in older adults with obesity while elucidating mechanisms governing musculoskeletal response to WL.