Strength Training and Arthritis Trial

描述（由申请人提供）：肌肉损失和脂肪增加会导致与膝骨关节炎（OA）相关的残疾、疼痛和发病率，而大腿肌肉无力是一个独立的、可改变的危险因素。已出版的治疗指南建议加强肌肉以对抗骨骼肌减少症并改善膝关节OA患者的肌肉质量；然而，之前的力量训练研究要么使用低于推荐水平的强度，要么通常较短（6至24周）。因此，它们具有低至中等的效应大小，不能检测疾病进展的变化，不能解决潜在的OA机制，并且几乎没有提供持久的临床益处。高强度力量训练在改善症状、减缓进展和影响潜在机制方面的功效尚未得到检验，因为未经证实的观点认为它可能加剧症状。我们的初步数据显示，老年膝关节OA患者对高强度力量训练的耐受性良好，疼痛减轻，功能增强。对健康老年人的类似研究发现，经过16-18周的训练后，大腿肌肉量有所改善，大腿脂肪量有所减少，而体重变化很小。我们建议对患有膝关节OA的老年人进行为期18个月的高强度力量训练干预，重点是改善大腿成分。我们假设，除了短期的临床益处外，结合更长的持续时间和高强度将足以改变大腿成分，从而实现膝关节力量的长期变化，减少炎症，降低疼痛水平，减缓进展。参与者（年龄55岁，体重指数25 kg/m2和40 kg/m2）将被随机分为三组：高强度力量训练（75-90% 1RM）；低强度力量训练（30-40%1RM）；或者是注意力控制。研究样本将包括372名社区居民，他们患有：(1)轻度至中度内侧胫股骨关节炎（KL = 2-3）；(2)膝关节内翻错位（内翻角e 2度，d 10度）；(3)在过去6个月内，每周没有参加超过30分钟的正式力量训练项目。主要临床目的是比较干预措施对膝关节疼痛的影响，主要机制目的是比较它们对行走时膝关节压缩力的影响，这是影响OA疾病途径的机制。次要目的是比较干预对疾病严重程度的其他临床指标的影响；通过MRI测量疾病进展；大腿肌肉和脂肪体积，通过CT测量；大腿肌肉功能的组成部分，包括髋外展肌力量和股四头肌力量、力量和本体感觉；膝关节负荷的附加措施；炎症和OA生物标志物。这项研究在三个方面具有创新性。首先，它测试了适用于老年膝关节OA患者的高强度力量训练方案的有效性。其次，它考虑了临床和机械结果。第三，它结合了运动强度和持续时间，以确定一种能够改善临床症状和减缓疾病进展且副作用最小的非药物治疗方法。

DESCRIPTION (provided by applicant): Muscle loss and fat gain contribute to the disability, pain, and morbidity associated with knee osteoarthritis (OA), and thigh muscle weakness is an independent and modifiable risk factor for it. Published treatment guidelines recommend muscle strengthening to combat sarcopenia and improve muscle quality in knee OA patients; however, previous strength-training studies either used intensities below recommended levels or were generally short (6 to 24 weeks). Consequently, they had low-to-modest effect sizes, could not detect changes in disease progression, did not address underlying OA mechanisms, and provided little lasting clinical benefit. The efficacy of high intensity strength training in improving symptoms, slowing progression, and affecting the underlying mechanisms has not been examined due to the unsubstantiated belief that it might exacerbate symptoms. Our preliminary data show excellent tolerance for high-intensity strength training as well as reduced pain and increased function among older adults with knee OA. Similar studies in healthy older adults found improvements in thigh muscle mass and decreases in thigh fat mass with minimal alteration in total body weight after 16-18 weeks of training. We propose an 18-month, high-intensity strength-training intervention for older adults with knee OA, focused on improving thigh composition. We hypothesize that in addition to short- term clinical benefits, combining greater duration with high intensity will alter thigh composition sufficiently to attain long-term changes in knee-joint forces, decrease inflammation, lower pain levels, and slow progression. Participants (age e 55 yrs; BMI e 25 kg/m2 and d 40 kg/m2) will be randomized to one of 3 groups: high- intensity strength training (75-90% 1RM); low-intensity strength training (30-40%1RM); or attention control. The study sample will consist of 372 ambulatory, community-dwelling persons with: (1) mild-to-moderate medial tibiofemoral OA (KL = 2-3); (2) knee varus malalignment (varus angle e 2 degrees and d 10 degrees); and (3) no participation in a formal strength-training program for more than 30 minutes per week within the past 6 months. The primary clinical aim is to compare the interventions' effects on knee pain, and the primary mechanistic aim is to compare their effects on knee-joint compressive forces during walking, a mechanism that affects the OA disease pathway. Secondary aims will compare intervention effects on additional clinical measures of disease severity; disease progression, measured by MRI; thigh muscle and fat volume, measured by CT; components of thigh muscle function, including hip abductor strength and quadriceps strength, power, and proprioception; additional measures of knee-joint loading; and inflammatory and OA biomarkers. This study is innovative in three ways. First, it tests the efficacy of a high-intensity strength training protocol suitable for an older population with knee OA. Second, it considers both clinical and mechanistic outcomes. Third, it combines exercise intensity and duration to identify a nonpharmacologic therapy capable of improving clinical symptoms and slowing disease progression with minimal adverse effects.