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

膝关节骨关节炎风险人群放射前病变的长期意义

• 批准号: 9061600
• 负责人: Leena Sharma
• 金额: $ 143.77万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9061600
• 关键词: American; Ancillary Study; Bone Marrow; Bone Spur; Cartilage; Clinic; Clinical; Clinical Trials Design; Contracture; Data; Data Collection; Degenerative polyarthritis; Development; Disease; Disease Progression; Epidemiologic Studies; Event; Funding; Future; Health; Individual; Intervention; Investigation; Knee; Knee Osteoarthritis; Knowledge; Learning; Lesion; Life; Literature; Longevity; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Motion; Nature; Onset of illness; Organ; Participant; Patient Self-Report; Performance; Persons; Physical Examination; Physical Function; Prevention strategy; Process; Reporting; Rheumatology; Risk; Risk Factors; Symptoms; System; Time; Tissues; Visit; Woman; Work; base; bone; clinical research site; clinically significant; college; follow-up; high risk; men; persistent symptom; prevent; research clinical testing; success; therapy development

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.

描述（由申请人提供）：开发膝关节骨关节炎（OA）疾病缓解疗法的主要障碍是疾病进展的性质，即涉及许多组织的螺旋式下降。在这一过程开始之前，改变疾病进程的可能性可能最高。文献记录了一些无放射学OA的老年人膝关节的软骨、骨和关节病变，但没有揭示它们是否代表早期OA。我们建议进行一项长期的纵向研究，以评估膝关节骨性关节炎风险较高但基线时X线检查无膝关节骨性关节炎的患者中此类病变的临床意义，以提高对早期骨性关节炎的认识，并帮助确定更早（比X线检查更早）的骨性关节炎发作窗口。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名膝关节OA患者或膝关节OA风险较高的患者进行的研究，在96个月时进行了随访。1244名参与者在基线时没有膝关节OA的X线检查结果。我们建议在120个月时对该子队列（1226例存活患者）进行额外访视，以收集数据（有些在基线后未收集，有些在48个月访视后未收集），以便在OAI临床研究中心仍在组建的最远可行时间点对OA的临床定义进行全面评价，并评估在96个月时收集的MR图像。拟议的目标是独特的，具有时间敏感性，无法在审调处的工作范围内完成。我们在该子队列中的OAI参与者中提出了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、膝关节撕裂、膝关节挤压）与历史膝关节OA事件风险之间的相关性，（和当前）放射学标准为120个月，最近提出的MRI标准为96个月; 2）评估基线时通过MRI检查的每个病变与膝关节OA的偶发临床特征风险之间的相关性，包括120个月时的ACR标准、屈曲挛缩和持续膝关节症状;和3）探索基线时MRI检查的每个病变与基线至120个月时通过表现和自我报告功能测量的身体功能下降之间的相关性。拟议的研究结果将使未来能够确定风险因素， 临床上重要的早期病变和预防策略，可以在生命早期引入。最终，在整个器官进展螺旋之前，具有临床意义的病变可能成为疾病修饰干预的目标，此时成功可能更容易实现。