Synovitis mediates the association between medial meniscal extrusion and subchondral bone denudation in knee osteoarthritis: Data from the FNIH OA biomarkers consortium

BACKGROUND: Medial meniscal extrusion (MME) accelerates structural progression in knee osteoarthritis (KOA). While its biomechanical impact has been established, its relationship with subchondral bone denudation and the potential mediating role of synovitis remain unclear. PURPOSE: This study aimed to investigate the association between MME in the absence of medial meniscal posterior root tears and the size of denuded areas of subchondral bone (dABs), and to evaluate whether synovitis mediates this relationship. METHODS: Data from the Foundation for the National Institutes of Health (FNIH) Osteoarthritis Biomarkers Consortium were analyzed. MME and synovitis (effusion-synovitis and Hoffa-synovitis) were assessed semi-quantitatively using the MRI Osteoarthritis Knee Score (MOAKS) system. The size of medial tibiofemoral dABs was quantified at baseline and 24-month follow-up. Linear regression models evaluated cross-sectional and longitudinal associations. Causal mediation analysis was conducted to quantify the proportion of the total effect of MME on dABs mediated by synovitis. RESULTS: A total of 520 participants were included. Cross-sectionally, both baseline MME (β = 2.03,95 % CI: 0.67, 3.38) and synovitis score (β = 0.97,95 % CI: 0.48, 1.46) were significantly associated with central medial femoral (cMF) dABs. Longitudinal analysis revealed significant correlations between MME and both 24-month cMF dABs (β = 3.41,95 % CI: 1.49,5.33) and 24-month medial tibial (MT) dABs (β = 0.98,95 % CI: 0.47,1.87). Furthermore, the 24-month synovitis score showed significant associations with both cMF dABs (β = 2.06,95 % CI: 1.38,2.74) and MT dABs (β = 0.88,95 % CI: 0.55,1.21). Mediation analysis indicated that synovitis mediated 20.1 % (95 % CI: 6.6, 71.1) of the effect of MME on baseline cMF dABs. 24-month synovitis mediated 20.38 % (95 % CI: 6.61, 44.50) of the effect of MME on 24-month cMF dABs and 16.86 % (95 % CI: 2.71, 42.16) of its effect on 24-month MT dABs. CONCLUSION: MME and dABs showed significant correlations in both cross-sectional and longitudinal studies. Synovitis acted as a mediator between MME and dABs, suggesting that inflammatory pathways may be involved in the pathological mechanisms of MME promoting KOA progression.