Intensive Dietary Restriction with Exercise in Arthritis

描述（由申请人提供）：关节炎在美国已达到流行病的比例。它是导致残疾的主要原因，影响到大约三分之一的成年人。骨关节炎（OA）是最常见的关节炎形式，保守估计有2100万美国人患病，占成年人口的12.1%。我们最近发现，患有膝关节OA的肥胖成年人体重减轻5%对临床结局的影响不大;然而，这些参与者在干预结束时仍然肥胖，因此他们的疾病进展风险没有改变。事实上，体重减轻与疾病进展相关机制之间关系的性质尚未确定。我们假设，更密集的体重减轻（比以前在这一人群中达到的体重减轻2至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、患有单侧或双侧膝关节胫股骨关节炎的老年（年龄> 60岁）成人。参与者将被随机分配到3个为期24个月的干预措施之一：强化饮食限制加运动;仅运动;或仅强化饮食限制。主要目的是比较这些干预措施对超重和肥胖成人膝关节OA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和疼痛以及活动性的影响;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介质，对功能、疼痛和疾病进展有显著影响;并确定股四头肌力量和疾病进展之间的关联作为膝关节对准的函数。体重减轻是膝关节骨性关节炎最易改变的风险因素;然而，没有研究确定对该人群有益的体重减轻程度。这项研究可以使强化减肥成为超重和肥胖成人膝关节OA的标准治疗，因为它增强了我们对OA疾病过程和老年人减肥建议的理解。

DESCRIPTION (Provided By Applicant): Arthritis has reached epidemic proportions in the United States. It is the leading cause of disability, affecting about one-third of adults. 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. Indeed, the nature of the relationships between weight loss and the mechanisms associated with disease progression are undetermined. 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, 24-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. Weight loss is the most modifiable risk factor for knee OA; however, no study has determined the extent of weight loss that is beneficial for this population. This study could make intensive weight loss the standard-of- care for overweight and obese adults with knee OA, as it enhances our understanding of the OA disease process and weight-loss recommendations for older people generally.