IDEA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 骨关节炎(OA)是最常见的关节炎形式，保守估计美国人的患病率为2100万，占成年人口的12.1%。我们最近发现，在患有膝骨性关节炎的肥胖成年人中，体重减轻5%对临床结果的影响不大；然而，这些参与者在干预结束时仍然肥胖，因此他们疾病进展的风险没有改变。我们假设，更高强度的减肥(比以前在该人群中实现的减肥效果高2到3倍)将提供必要的刺激，以减少炎症和关节负荷，并改变疾病进展。 研究人群将包括450名超重和肥胖的老年人(年龄=60岁)，他们患有单膝或双膝的胫股骨性关节炎。参与者将随机接受为期3个月、为期18个月的干预措施：强化饮食限制加锻炼；仅锻炼；或仅强化饮食限制。主要目的是比较这些干预措施对患有膝骨性关节炎的超重和肥胖成年人的炎症生物标志物和膝关节负荷的影响。次要目标是：比较这些干预措施对自我报告的功能、疼痛和活动能力的影响；确定体重减轻对疾病进展的剂量反应以及与OA疾病途径相关的机制；确定炎症生物标志物和膝关节负荷是否是干预措施的媒介，对功能、疼痛和疾病进展有显著影响；以及确定股四头肌力量和疾病进展之间作为膝关节排列的函数的关联。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Osteoarthritis (OA) is the most common form of arthritis with a prevalence conservatively estimated at 21 million Americans, or 12.1% of the adult population. We recently showed that a 5% weight loss in obese adults with knee OA had a modest effect on clinical outcomes; however, these participants remained obese at the conclusion of the intervention, so their risk of disease progression was not altered. We hypothesize that a more intensive weight loss (2 to 3 times greater than previously achieved in this population) would provide the stimulus necessary to reduce inflammation and joint loads and alter disease progression. The study population will consist of 450 overweight and obese, older (age = 60 yrs) adults with tibiofemoral osteoarthritis of one or both knees. Participants will be randomized to 1 of 3, 18-month interventions: intensive dietary restriction-plus-exercise; exercise-only; or intensive dietary restriction-only. The primary aim is to compare the effects of these interventions on inflammatory biomarkers and knee joint loads in overweight and obese adults with knee OA. Secondary aims are: to compare the effects of these interventions on self-reported function and pain, and mobility; to determine the dose response to weight loss on disease progression and the mechanisms associated with the OA disease pathway; to determine if inflammatory biomarkers and knee joint loads are mediators of the interventions, with significant effects on function, pain, and disease progression and to determine the association between quadriceps strength and disease progression as a function of knee alignment.