Abstract

Anti-catabolic disease modifying drugs (DMOADs) aim to reduce cartilage loss in knee osteoarthritis (KOA). Testing such drugs in clinical trials requires sufficient rates of loss in the study participants to occur, preferably at a mild disease stage where cartilage can be preserved. Here we analyze a "progression" model in mild radiographic KOA (RKOA), based on contra-lateral radiographic status. We studied 837 participants (62.4 ± 9 yrs; 30 ± 4.9 kg/m²; 61.8% women) from the Osteoarthritis Initiative (OAI) with mild to moderate RKOA (Kellgren Lawrence grade [KLG] 2-3) and with/without Osteoarthritis Research Society International (OARSI) atlas radiographic joint space narrowing (JSN). These had quantitative measurements of subregional femorotibial cartilage thickness from magnetic resonance imaging (MRI) at baseline and 1-year follow-up. They were stratified by contra-lateral knee status: no (KLG 0/1), definite (KLG2) and moderate RKOA (KLG 3/4). KLG2 knees with JSN and moderate contra-lateral RKOA had (P = 0.008) greater maximum subregional cartilage loss -220 μm [95% confidence interval (CI) -255, -184 μm] than those without contra-lateral RKOA -164 μm [-187, -140 μm]. Their rate of subregional cartilage loss was similar and not significantly different (P = 0.61) to that in KLG 3 knees without contra-lateral RKOA (-232 μm; [-266; -198 μm]). The effect of contra-lateral RKOA status was less in KLG2 knees without JSN, and in KLG3 knees. KLG2 knees with JSN and moderate contra-lateral RKOA, display relatively high rates of subregional femorotibial cartilage loss, despite being at a relatively mild stage of RKOA. They may therefore provide a unique opportunity for recruitment in clinical trials that explore the efficacy of anti-catabolic DMOADs on structural progression.

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