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膝关节骨关节炎(OA)相关的残疾、疼痛和发病率，而大腿肌肉无力是其独立的和可修改的危险因素。已公布的治疗指南建议膝关节骨性关节炎患者加强肌肉力量以对抗骨质疏松症和改善肌肉质量；然而，以前的力量训练研究要么使用低于推荐水平的强度，要么通常使用较短的强度(6至24周)。因此，它们具有低到中等的效应大小，不能检测到疾病进展的变化，没有解决潜在的骨关节炎机制，并且几乎没有提供持久的临床益处。大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有效性尚未得到检验，因为人们认为高强度力量训练可能会加剧症状。我们的初步数据显示，在患有膝骨性关节炎的老年人中，对高强度力量训练的极好耐受性以及疼痛的减轻和功能的增加。在健康的老年人中进行的类似研究发现，在16-18周的训练后，大腿肌肉质量有所改善，大腿脂肪质量下降，而总体重变化很小。我们建议对患有膝骨性关节炎的老年人进行为期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，更长的持续时间和高强度的结合将充分改变大腿的成分，从而实现膝关节力量的长期变化，减少炎症，降低疼痛水平，并减缓进展。受试者(年龄e 55岁；体重指数e 25 kg/m2和d 40 kg/m2)将被随机分为3组：高强度力量训练(75-90%1rm)；低强度力量训练(30-40%1rm)；或注意力控制。研究样本将包括372名活动的社区居民，他们有：(1)轻度至中度胫股内侧骨关节炎(KL=2-3)；(2)膝关节内翻畸形(内翻2度和d 10度)；以及(3)在过去6个月内每周不参加正式力量训练计划超过30分钟。主要的临床目的是比较干预措施对膝关节疼痛的效果，而主要的机制目的是比较它们对步行过程中膝关节压力的影响，这是影响膝骨性关节炎疾病途径的机制。二级目标将比较其他临床测量的干预效果，这些测量包括疾病严重程度；通过核磁共振测量的疾病进展；通过CT测量的大腿肌肉和脂肪体积；大腿肌肉功能的组成部分，包括髋外展肌力和股四头肌力量、力量和本体感觉；其他膝关节负荷测量；以及炎症和骨关节炎生物标记物。本研究在三个方面具有创新性。首先，它测试了一种适用于膝骨性关节炎老年人群的高强度力量训练方案的有效性。其次，它同时考虑了临床和机制结果。第三，它结合运动强度和持续时间来确定一种非药物疗法，能够以最小的不良反应改善临床症状和减缓疾病进展。

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.