Comparison of the therapeutic efficacies of methotrexate and aquatic exercise in an experimental knee osteoarthritis model

Objective: This study aimed to evaluate the isolated and combined effects of methotrexate (MTX) and aquatic exercise in a rat model of monosodium iodoacetate (MIA)–induced knee osteoarthritis (OA). Methods: Thirty male Wistar albino rats were divided into five groups: Sham, OA, Aquatic Exercise (S), Methotrexate (M), and Combined Treatment (SM). OA was induced via intra-articular injection of 3 mg MIA into both knees. Over six weeks, the S group followed a swimming-based exercise regimen, the M group received oral MTX, and the SM group underwent both treatments. Efficacy was assessed through the spontaneous extension test, gait analysis, bone morphometry via micro-computed tomography, and stereological and histopathological evaluations including cartilage volume, chondrocyte count, and proteoglycan density. Results: The OA group exhibited significant cartilage degeneration and functional decline. Compared to MTX alone, combined treatment led to greater improvements in spontaneous extension and gait. Histological analysis revealed that both the SM and M groups better preserved cartilage volume and proteoglycan density, though neither prevented chondrocyte loss. Micro-CT indicated limited effects of any treatment on OA-related bone microarchitecture deterioration. Conclusion: The combination of aquatic exercise and MTX synergistically reduced pain-related behaviors and helped preserve cartilage matrix integrity. These results support the concurrent use of pharmacological and physical therapies as a potential strategy for symptomatic relief and partial structural protection in osteoarthritis.