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Objective To assess whether the presence of structural osteoarthritis (OA) features over as many as 4 years prior to incident radiographic OA increases the risk of radiographic OA in a nested, case-control design. Methods We studied 355 knees from the Osteoarthritis Initiative cohort that developed radiographic OA before the 48-month visit. They were matched one-to-one by sex, age, and contralateral knee radiographic status with a control knee. Magnetic resonance images (MRIs) were read for bone marrow lesions (BMLs), cartilage damage, meniscal damage (including tears and extrusion), Hoffa synovitis, and effusion synovitis. Conditional logistic regression was applied to assess the risk of radiographic OA with regard to the presence of BMLs (score ≥2), cartilage lesions (score ≥1.1), meniscal damage (any) and extrusion of ≥3 mm ± (score ≥2), and Hoffa and effusion synovitis (any). Time points were defined as incident radiographic OA visit (P0), 1 year prior to the detection of radiographic OA (P −1), 2 years prior to the detection of radiographic OA (P −2), etc. Results The presence of Hoffa synovitis (hazard ratio [HR] 1.76 [95% confidence interval (95% CI) 1.18-2.64]), effusion synovitis (HR 1.81 [95% CI 1.18-2.78]), and medial meniscal damage (HR 1.83 [95% CI 1.17-2.89]) at P −2 predicted radiographic OA incidence. At P −1, all features but meniscal extrusion predicted radiographic OA, with highest odds for medial BMLs (HR 6.50 [95% CI 2.27-18.62]) and effusion synovitis (HR 2.50 [95% CI 1.76-3.54]). The findings at P −3 and P −4 did not reach statistical significance. Conclusion Our findings indicate that the presence of specific structural features of MRI-detected joint damage 2 years prior to incident radiographic OA increases the risk of incident radiographic OA. However, 1 year prior to radiographic OA, the presence of almost any abnormal morphologic feature increases the risk of radiographic OA in the subsequent year. [ABSTRACT FROM AUTHOR]