Long-term Significance of Pre-radiographic Lesions in Persons at Risk for Knee OA

描述（由申请人提供）：发展改善膝关节骨关节炎（OA）疾病治疗的主要障碍是疾病进展的性质，涉及许多组织的下行螺旋。在这一过程开始之前，改变疾病进程的可能性最大。文献记录了一些没有影像学骨性关节炎的老年人膝关节的MRI软骨、骨和半月板病变，但没有揭示它们是否代表早期骨性关节炎。我们建议进行一项长期的纵向研究，以评估这些病变在膝关节OA高风险人群中的临床意义，但在基线x线检查时双膝均无OA，以提高对早期OA的认识，并帮助确定更早的（比x线提供的）OA发病窗口。我们有一个非常独特的机会来进行这项研究。骨关节炎倡议（OAI）是一项对4796名患有或有较高膝关节炎风险的个体进行的研究，随访96个月。1244名参与者在基线时没有任何膝关节OA的x线表现。我们建议在120个月时对该亚队列（1226人）进行额外的访问，以收集数据（有些在基线后未收集，有些在48个月访问后未收集），以便在OAI临床位点仍然存在的情况下，在最远可行的时间点对OA的临床定义进行全面评估，并评估96个月时收集的MR图像。拟议的目标是独特的、时间敏感的，不可能在审计办公室的工作范围内完成。我们在这一亚队列中提出了OAI参与者的3个目标：1)通过基线时的MRI评估每种病变（软骨损伤、骨髓病变、半月板撕裂、半月板挤压）与120个月的历史（和当前）放射学标准和96个月的最近提出的MRI标准评估发生膝关节OA的风险之间的关系；2)在基线时通过MRI评估每个病变与膝关节OA事件临床特征（包括ACR标准、屈曲挛缩和持续120个月的膝关节症状）的风险之间的关系；3)通过MRI研究各病变在基线和基线至120个月的身体功能下降（表现和自我报告功能测量）之间的关系。拟议的研究结果将使未来确定的风险因素

DESCRIPTION (provided by applicant): A major barrier to development of disease-modifying therapy for knee osteoarthritis (OA) is the nature of disease progression, a downward spiral involving many tissues. The potential for changing disease course may be highest before this process is in motion. The literature documents cartilage, bone, and meniscal lesions by MRI in knees of some older individuals without radiographic OA, but does not reveal whether they represent early OA. We propose a long-term, longitudinal study to evaluate the clinical significance of such lesions in persons at higher risk for knee OA but without OA in either knee by x-ray at baseline, to advance knowledge of early OA and to help to identify an earlier (than x-ray affords) OA onset window. We have a highly unique opportunity to carry out this study. The Osteoarthritis Initiative (OAI), a study of 4796 individuals with or at higher risk for knee OA, ens follow-up at 96 months. 1244 participants had no x-ray findings of knee OA in either knee at baseline. We propose an additional visit of this subcohort (1226 living) at 120 months to collect data (some not collected after baseline and some not after the 48 month visit) that would enable comprehensive evaluation of clinical definitions of OA at the furthest feasible time point while the OAI clinical sites are still constituted, as well as assessment of MR images being collected at 96 months. The proposed aims are unique, time-sensitive, and could not be completed within the OAI's scope of work. We propose 3 aims in OAI participants in this subcohort: 1) evaluate the association between each lesion - cartilage damage, bone marrow lesion, meniscal tear, meniscal extrusion - by MRI at baseline and risk of incident knee OA by the historic (and current) radiographic criterion by 120 months and by recently proposed MRI criteria by 96 months; 2) evaluate the association between each lesion by MRI at baseline and risk of incident clinical features of knee OA, including ACR criteria, flexion contracture, and persistent knee symptoms by 120 months; and 3) explore the association between each lesion by MRI at baseline and baseline-to-120-month physical function decline by performance and self-report measures of function. Proposed study findings will enable future identification of risk factors for clinically important early lesions and prevention strategies that could be introduced earlier in th lifespan. Ultimately, clinically significant lesions might become a target of disease-modifying intervention at a point when success may be more realizable, before the whole-organ progression spiral.