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

项目摘要 老年和肥胖是发病率和死亡率的普遍危险因素。体重减轻（WL）改善了许多 肥胖的临床后果;然而，尽管有其好处，建议在老年人中进行有意WL 仍然存在争议。不愿干，至少部分，从骨质流失已知伴随整体 WL和与年龄相关的骨质疏松症和骨折风险恶化的可能性。增加阻力 针对WL的运动训练（RT）是减轻但不能阻止WL相关骨减少的有效手段 矿物质密度（BMD）;然而，传统的RT干预存在长期可行性的障碍（即， 昂贵的设备、现场参与、由训练有素的工作人员进行安全监督以及合规性下降）。 或者，通过外部替代失去的重量来治疗WL相关的机械应力降低， 还能保存骨量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）在降低WL相关的髋部BMD损失方面是可行的， 增加骨形成的生物标志物。如果得到证实，更大的可用性，易于管理， 与RT相比，使用加重背心来抵消WL相关骨丢失的成本降低， 公共卫生潜力作为一种可转化的策略，以最大限度地提高WL的心脏代谢益处， 最大限度地减少对肌肉骨骼系统的负面影响。拟议R 01研究的主要目标是 比较单独使用WL和使用负重背心或RT对骨骼健康的几个指标的影响， 随后的骨折风险。我们建议在192名老年（65-79岁）肥胖（BMI=30- 40）成人中进行一项为期12个月的试验。 40 kg/m2）随机分配至三种干预措施之一（n=64/组）：单独WL（WL;热量限制目标 10% WL并遵循国家肥胖治疗指南）; WL+负重背心使用（WL+VEST; ≥6 小时/天，体重替代滴定至10%WL）;或WL+结构化RT（WL+RT; 3天/周，10 练习，10-12次重复）。我们的主要研究结果是12个月后全髋小梁体积的变化 我们假设，尽管总体重有类似的减少：（1）参与者在 WL+VEST组与WL组相比，全髋骨小梁vBMD的丢失减弱，（2）全髋骨小梁vBMD的丢失 与WL+ RT相比，WL+VEST中的小梁vBMD不会更大。在一位才华横溢的新研究者的带领下， 提案是PI当前MRSDA（K 01 AG 047291）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有意WL的可翻译策略， 同时阐明了肌肉骨骼对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.