Synovitis mediates the association between bone marrow lesions and knee pain in osteoarthritis: data from the Foundation for the National Institute of Health (FNIH) Osteoarthritis Biomarkers Consortium

Objectives Although subchondral bone marrow lesions (BMLs) and synovitis have been well acknowledged as important sources of pain in knee osteoarthritis (KOA), it is unclear if synovitis plays the mediating role in the relationship between BMLs and knee pain. Methods We analyzed 600 subjects with magnetic resonance imaging (MRI) in the Foundation for National Institutes of Health Osteoarthritis Biomarkers Consortium (FNIH) cohort at baseline and 24-month. BMLs and synovitis were measured according to the MRI Osteoarthritis Knee Score (MOAKS) scoring system. BMLs were scored in five subregions. A summary synovitis score of effusion and Hoffa-synovitis was calculated. Knee pain was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Linear regression models were applied to analyze the natural direct effect (NDE) of BMLs and synovitis with knee pain, respectively, and natural indirect effect (NIE) mediated by synovitis. Results 590 participants (58.8% females, with a mean age of 61.5) were included in the present analyses. For NDE, knee pain was cross-sectionally associated with medial femorotibial BMLs (β = 0.23, 95% CI: 0.09, 0.38) and synovitis (β = 0.40, 95% CI: 0.20, 0.60). Longitudinal associations retained significant [medial femorotibial BMLs (β = 0.37, 95% CI: 0.21, 0.53); synovitis (β = 0.72, 95% CI: 0.45, 0.99)]. In the NIE analyses, synovitis mediated the association between medial femorotibial BML and knee pain at baseline (β = 0.051, 95% CI: 0.01, 0.09) and over 24 months (β = 0.079, 95% CI: 0.023, 0.15), with the mediating proportion of 17.8% and 22.4%, respectively. Conclusion Synovitis partially mediates the association between medial femorotibial BMLs and knee pain.