Multicenter Osteoarthritis Study (MOST) Renewal

描述（由申请人提供）：骨关节炎（OA）是关节炎的最常见形式，并且仍然是为数不多的老年慢性疾病之一，即使有有效的治疗方法和预防策略，也很少。症状性膝关节骨关节炎影响12%的老年人，尽管医学进步，仍然是许多受影响的主要来源的疼痛和功能限制。MOST研究是第一个大规模的观察性研究，重点关注膝关节骨关节炎患者或高危人群。社会变革管理计划的中心目标是确定可改变的风险因素。为了实现这一目标，我们招募并随访了3026名基线时患有膝关节骨关节炎或因具有一种或多种疾病风险因素而处于疾病高风险中的人。我们建议延长社会变革管理计划。在继续跟踪这一独特的队列研究时，我们将解决一系列代表三个研究主题的新问题：机械风险因素、膝关节症状的原因和长期疾病轨迹。对基于负荷影响膝关节的风险因素的关注反映了MOST研究者的观点，即OA是一种机械驱动的疾病。机械风险因素可能与疾病风险密切相关，并且可以改变。疼痛是OA的主要症状，也是其临床和公共卫生影响的主要原因。对疼痛敏感性的研究旨在更好地了解维持或放大OA症状的神经机制。与膝关节OA相关的另一个症状是膝关节屈曲，其频率和影响最近才被描述，其与老年人福尔斯和骨折的相关性尚不清楚。最后，我们将利用关于功能丧失和重复MRI的综合信息的两个资助周期来解决这种慢性疾病的长期轨迹。在MOST研究的更新中，我们将重新检查一组已经患有疾病或处于高风险的人群，以评估疾病的风险因素。那些被证明与疾病发展或进展相关的因素可以作为风险因素修改的目标，为疾病预防提供独特的机会。要研究的风险因素包括许多实际的修改，包括力量，行走方式和平衡。此外，MOST将提供对膝关节结构变化及其对疼痛和功能影响之间关系的最佳理解，为治疗提供结构目标。

DESCRIPTION (provided by applicant): Osteoarthritis (OA) is the most common form of arthritis and remains one of the few chronic diseases of aging for which there is little if any effective treatment and few preventive strategies. Symptomatic knee osteoarthritis affects 12% of elders and despite medical advances, remains, for many affected, a major source of pain and function limitation. The MOST study is the first large scale observational study to focus on persons with or at high risk of knee osteoarthritis. The central goal of MOST is to identify modifiable risk factors. To accomplish this, we recruited and have followed 3026 persons who either had knee osteoarthritis at baseline or were at high risk of developing disease because they had one or more disease risk factors. We are proposing a renewal of MOST. In continuing to follow this unique cohort, we will address a series of new questions representing three investigative themes: mechanical risk factors, causes of knee symptoms and long term disease trajectory. The focus on risk factors which affect knees on the basis of loading reflects the view of MOST investigators that OA is a mechanically driven disease. Mechanical risk factors are likely to be both strongly associated with disease risk and modifiable. Pain is the cardinal symptom of OA and the main cause of its clinical and public health impact. An investigation of pain sensitivity seeks to better understand the neurological mechanisms that sustain or magnify OA symptoms. Another symptom associated with knee OA is knee buckling, whose frequency and impact has only recently been described and whose association with falls and fractures in older adults is unknown. Lastly, we will take advantage of two grant cycles of comprehensive information on functional loss and repeated MRI's to address the long term trajectory of this chronic disease. In this renewal of the MOST study we will re-examine a group of persons who already have disease or are at high risk of getting it, to evaluate the risk factors for disease. Those factors that prove to be related to disease development or progression could then be targeted for risk factor modification offering unique opportunities for disease prevention. Risk factors to be studied include many which are practical to modify, including strength, ways of walking, and balance. Also, MOST will provide the best understanding yet of the relation between changes in knee structures and their effects on pain and function, providing structural targets for treatment.