Preventing Incident Knee Osteoarthritis: The Osteoarthritis Prevention Study (TOPS)

摘要 骨关节炎（OA）是老年人残疾的主要原因;在没有治愈的情况下， 必须采取初级预防措施。本R34的目的是计划评估员- 设盲、48个月、多中心、随机临床试验，旨在（a）建立强化饮食， 运动是预防膝关节骨性关节炎并发症的有效干预措施;以及 (b)确定这种非药物干预在预防事件中的成本效益 高风险成年女性中的症状性、影像学膝关节OA。 大量的观察数据表明，旨在减弱关节负荷的干预措施 运动和减肥引起的炎症显示出预防膝关节OA发作的希望。 更大的体重减轻与胫骨内侧间室更好的软骨健康相关，包括 质量（蛋白聚糖含量增加）和数量（软骨变弱）的改善 厚度损失）的内侧关节软骨。数据还表明，损失少至5公斤或5%的 基线体重可能导致发生放射学膝关节OA的风险降低3倍 肥胖妇女的情况。我们的长期强化减肥和锻炼的方法是一种非- 最近在IDEA试验中测试的患有膝关节OA的肥胖成人的药物治疗引起了 膝关节负荷和促炎细胞因子显著降低， 功效总之，这些研究为我们的研究提供了临床和机制基础。 前提是饮食减肥≥10%体重结合运动将改善长期 临床结局（疼痛和功能），并通过关节复位预防相对于对照组的膝关节OA事件 负荷，降低炎症，并提高自我效能的减肥在高危女性。 FDA认为OA是一种严重的疾病，医疗需求未得到满足。OA的重要性 疾病预防是显而易见的，因为我们目前没有有效的疾病改善干预措施， 许多止痛药都存在安全隐患，而且无法治愈。这 规划补助金将提供支持，以进行示范招聘，以测试可行性，建立中央 IRB，完善研究方案以及保留和依从计划，最终确定统计分析计划，以及 完成操作程序手册。我们还将建立和测试一个集中的阅读 所有X光片的协议，为介入医生制定培训手册，以及详细的项目时间轴 用于未来的临床试验。

Abstract Osteoarthritis (OA) is the leading cause of disability among older adults; in the absence of a cure, the need for primary preventive measures is essential. The objective of this R34 is to plan an assessor- blinded, 48-month, multi-center, randomized clinical trial designed to (a) establish intensive diet and exercise as an efficacious intervention for preventing incident symptomatic, radiographic knee OA; and (b) determine the cost-effectiveness of this non-pharmacologic intervention in preventing incident symptomatic, radiographic knee OA in high risk adult females. A substantial body of observational data suggests that interventions designed to attenuate joint loading and inflammation by exercise and weight loss show promise in preventing the onset of knee OA. Greater weight loss is associated with better cartilage health in the medial tibial compartment, including improvements in the quality (increased proteoglycan content) and quantity (attenuated cartilage thickness loss) of medial articular cartilage. Data also indicate that losing as little as 5 kg or 5% of baseline weight may result in as much as a 3-fold reduction in the risk of incident radiographic knee OA in obese women. Our approach of long-term intensive weight loss and exercise as a non- pharmacologic treatment for obese adults with knee OA recently tested in the IDEA trial elicited significant reductions in knee joint loads and pro-inflammatory cytokines, and improvements in self- efficacy. Taken together, these studies provide the clinical and mechanistic underpinning for our premise that dietary weight loss of ≥10% of body weight combined with exercise will improve long-term clinical outcomes (pain and function) and prevent incident knee OA relative to control by reducing joint loads, lowering inflammation, and improving self-efficacy for weight loss in at-risk females. The FDA recognizes OA as a serious disease with an unmet medical need. The importance of OA disease prevention is evident because we presently have no effective disease-modifying interventions, there are substantial safety concerns associated with many pain medications, and there is no cure. This planning grant will provide support to conduct a model recruitment to test feasibility, establish a central IRB, refine the study protocol and retention and adherence plans, finalize a statistical analysis plan, and complete the manual of operating procedures. We will also establish and test a centralized reading protocol for all radiographs, develop training manuals for interventionists, and a detailed project timeline for the future clinical trial.