THE EFFECTS OF HIGH-DOSE METHOTREXATE ON THE DEVELOPMENT OF CARTILAGELESIONS IN A LAPINE MODEL OF OSTEOARTHROSIS

To determine whether systemic administration of methotrexate (MTX) can prevent joint destruction in experimental osteoarthrosis (OA) in rabb its, the disorder was induced unilaterally in the knee joints of 40 ra bbits by partial medial meniscectomy and sectioning of the medial coll ateral and both cruciate ligaments. A sham operation (arthrotomy only) was performed in another four animals. Effects on the cartilage of th e femoral condyles were studied after 6 and 12 weeks. Twelve weeks aft er induction, femoral and tibial osteophyte formation was demonstrated on radiographs in all cases. Marked cartilage damage was found histol ogically (median Mankin score 10 vs 1 for non-operated controls, P < 0 .05, Wilcoxon test). Cartilage proteoglycan (GAG) content (dye binding assay) was reduced in operated joints [63 +/- 8 (mean +/- SEM) vs 75 +/- 6 mu g chondroitin sulfate/mg cartilage wet weight], and the leuko cyte count in the joints was elevated (226 +/- 14 vs 7 +/- 3 leukocyte s per mu 1 joint aspirate after injection of 0.5 mi saline solution, b oth P < 0.05, Wilcoxon test). The rate of GAG synthesis was unchanged (ex vivo labelling with S-35-sulfate). Treatment with MTX (30 mg x kg body weight(-1) x week(-1) i.m., starting 12 h postoperatively) reduce d cartilage damage (median Mankin score 8 vs 10 for placebo, P < 0.05. Mann-Whitney U-test), but had no significant effect on the other para meters tested. No significant MTX effects were observed on cartilage f rom nonoperated joints. Our data indicate that MTX may have a limited therapeutic effect in experimental OA in the rabbit.