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(申请人提供)：膝关节骨关节炎(OA)疾病修正疗法发展的一个主要障碍是疾病进展的性质，即涉及许多组织的向下螺旋。在这一过程开始之前，改变病程的可能性可能最大。这些文献记录了一些没有放射学骨性关节炎的老年人膝关节的软骨、骨和半月板的MRI损伤，但没有揭示它们是否代表早期的骨性关节炎。我们建议进行一项长期的、纵向的研究，以评估膝关节骨关节炎的高危人群中此类病变的临床意义，并通过基线的X线片，促进对早期骨性关节炎的认识，并帮助确定早期骨性关节炎的发病窗口。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)是一项针对4796名膝骨性关节炎风险较高或风险较高的个人的研究，ENS在96个月内进行了随访。1244名受试者在基线时的两个膝关节均无膝关节骨关节炎的X线表现。我们建议在120个月时对这一亚队列(活着的1226人)再进行一次访问，以收集数据(有些不是在基线之后收集的，有些不是在48个月的访问之后收集的)，以便能够在OAI临床站点仍然构成的情况下，在最远的可行时间点对OA的临床定义进行全面评估，以及对96个月时收集的MR图像进行评估。拟议的目标是独特的、对时间敏感的，不可能在审调处的工作范围内完成。我们在这个亚队列中的OAI参与者中提出了三个目标：1)在基线时通过MRI评估每个病变--软骨损伤、骨髓损伤、半月板撕裂、半月板突出--与根据历史(和当前)放射学标准120个月和最近提出的MRI标准96个月发生膝关节骨性关节炎的风险之间的关系；2)评估基线时的MRI每个病变与膝关节骨关节炎发生的风险之间的关系，包括ACR标准、屈曲痉挛和持续的膝关节症状120个月；3)通过功能表现和自我报告功能的测量，探索基线时MRI检查的每个损害与基线至120个月的身体功能下降之间的关系。拟议的研究结果将使未来能够确定以下风险因素 临床上重要的早期损害和预防策略，可以在生命周期的早期引入。最终，在整个器官进展螺旋之前，在成功可能更容易实现的时候，具有临床意义的病变可能成为疾病修改干预的目标。