Novel Insights into Osteoarthritis, Pain and Function: MOST4

总体摘要 多中心骨关节炎（MOST）研究是关于骨关节炎病程的新知识的主要来源。 OA和影响它的因素，发表了180多篇文章，从疼痛和疼痛的研究 致敏，生物力学的研究，通过MRI可视化的结构关节病理学的调查， 以及对功能下降、屈曲和福尔斯等的研究。初始队列招募了3026名参与者 患有膝关节OA或有膝关节OA风险;在最后一个周期（MOST 3）招募了一个由1525例受试者组成的新队列， 年龄稍小，不太可能患有晚期疾病。我们将招募150名来自 在社会变革管理计划下一个周期（社会变革管理计划4）中，预计抽样总数为2 293人。 除了科学产出，这项研究在招募和鼓励有才华的年轻人方面也很出色。 调查人员在社会变革管理计划内进行职业界定调查， 发展奖。我们的总体目标是推进我们对OA及其后果的理解， 新的治疗方法，包括分层治疗方法的大门。我们将使用集成 由管理核心监督下一个MOST周期（MOST 4）中的方法，涉及临床数据 收集和管理核心、分析核心和成像核心，并在观察安全性 监测委员会和社区咨询委员会的投入，以有效解决关键的知识差距 通过三个项目的实施。我们的具体目标是：1。评估运动诱导的受损 疼痛减退（EIH）在膝关节OA，评估神经系统的改变与EIH的关系，并确定 EIH对疼痛、功能、身体活动和与运动相关的恐惧避免的影响（项目1）; 2.开展 滑液的蛋白质组学分析，以确定与全身性与局部性 OA、疼痛和疾病进展（项目2）; 3.区分关节中沉积的钙晶体类型， 对于他们中的每一个，了解晶体沉积的临床和结构后果（项目3）; 4.采取 社会变革管理计划已经收集的全面纵向数据的优势，以解决广泛的问题 与OA及其对结果的影响有关; 5.采取多学科方法来应对这种复杂的疾病 并为研究人员提供职业发展机会，包括在这一未充分研究的领域提供试点项目赠款 条件MOST 4将采用新的方法来了解疾病，并将继续全面 评估疼痛，结构和功能结果，以便项目中提出的因素的具体影响 和其他风险因素可以检查。这项工作将产生新的可操作的见解，关于疼痛，结构 膝关节OA的恶化和功能丧失。

OVERALL ABSTRACT The Multicenter Osteoarthritis (MOST) Study has been a major source of new knowledge about the course of OA and factors that affect it, having published over 180 articles ranging from studies of pain and pain sensitization, to investigations of biomechanics, to inquiries into structural joint pathology as visualized by MRI, and to studies of decline in function, buckling and falls, among others. The initial cohort enrolled 3026 participants with or at risk of knee OA; a new cohort consisting of 1525 subjects was recruited at the last cycle (MOST3) who were slightly younger and unlikely to have advanced disease. We will recruit an additional 150 participants from underrepresented minority groups for a total projected sample size of 2293 in this next cycle of MOST (MOST4). In addition to its scientific output, the study has been remarkable in recruiting and encouraging talented young investigators to take on career defining investigations within MOST, having served as the basis for 31 career development awards. Our overall goal is to advance our understanding of OA and its consequences to open doors to new treatment approaches including stratified approaches to treatments. We will use an integrated approach in the next cycle of MOST (MOST4) overseen by an Administrative Core, involving a Clinical Data Collection and Management Core, Analysis Core, and Imaging Core, with guidance from an Observational Safety Monitoring Board and input from a Community Advisory Board, to efficiently address key knowledge gaps through the conduct of three Projects. Our Specific Aims are to: 1. Evaluate impaired exercise-induced hypoalgesia (EIH) in knee OA, evaluate the relation of nervous system alterations to EIH, and determine the impact of EIH on pain, function, physical activity, and fear-avoidance related to exercise (Project 1); 2. Carry out proteomics analysis of synovial fluid to determine networks of proteins associated with generalized vs. localized OA, pain and disease progression (Project 2); 3. Differentiate types of calcium crystals deposited in the joint and, for each of them, understand the clinical and structural consequences of crystal deposition (Project 3); 4. Take advantage of comprehensive longitudinal data already collected in MOST to address a wide range of questions related to OA and its impact on outcomes; 5. Bring a multidisciplinary approach to bear on this complex disease and offer career development opportunities to investigators including pilot project grants in this understudied condition. MOST4 will introduce new approaches to understanding disease and will continue to comprehensively assess pain, structural, and functional outcomes so that the specific effects of the factors proposed in the Projects and other risk factors can be examined. This work will produce new actionable insights regarding pain, structural deterioration and function loss in knee OA.