PROJECT SUMMARY/ABSTRACT Osteoarthritis (OA) is a complex, heterogeneous condition that is a major public health problem, the most common cause of disability in the aging population and is associated with a large economic burden. The pathophysiology of OA affects the whole joint, with breakdown of cartilage, associated changes in the subchondral bone and adjacent soft tissue that leads to debilitating symptoms such as pain. With the aging of the population and the epidemic of obesity, the public health impact of OA, especially knee OA, has and will continue to increase dramatically, but unfortunately, there are no FDA-approved disease-modifying OA drugs (DMOADs), i.e., drugs designed to impede or prevent the OA-related structural changes to cartilage and bone. This has been due to a lack of understanding of the relationship between features of OA and disease progression. MRI, however, has improved our understanding of the relationship between histopathologic changes and the structural changes to cartilage, subchondral bone and the surrounding soft tissues of the joint in OA. As such MRI represents an improvement over plain knee radiographs, which are both insensitive and nonspecific to critical changes in joint structure in the development and progression of OA. The objective of this work is to understand the impact of the trajectory of BMLs and ES on downstream clinical outcomes, including cartilage loss and disability, over the short-term (i.e., two years later) and long-term (i.e., six years later). Analysis of the trajectory of BMLs and ES will take into account the quantitative volume at baseline and the quantitative change in volume over time. The specific aims of this study are: To evaluate the impact of the trajectory of MRI-detected bone marrow lesions (BMLs) and effusion synovitis (ES) on subsequent cartilage loss; and to evaluate the impact of the trajectory of MRI-detected BMLs and ES on knee-specific disability.

PROJECT NARRATIVE Knee osteoarthritis is a very common and disabling disease. There are no approved treatments to stop or slow the structural changes of knee osteoarthritis or to prevent disability. This study will help to identify potential targets for new treatments to halt or slow disease progression or to prevent disability.