The effect of non-steroidal anti-inflammatory drugs on matrix metalloproteinases levels in patients with osteoarthritis

OBJECTIVE: The objective of this study is to determine and comparatively evaluate the effects of three different non-steroidal anti-inflammatory drugs on the levels of metalloproteinases MMP-1, MMP-3 and MMP-8, as well as on their tissue inhibitor TIMP-1, in patients suffering from idiopathic osteoarthritis. The effect of these drugs on the articular cartilage and the probable use of MMPs and TIMP-1 as markers of disease and treatment was also investigated. METHODS: Thirty-six patients with OA were selected and allocated to three groups on the basis of their disease location. All patients received anti-inflammatory treatment with special selective COX-2 inhibitors, i.e. celecoxib, meloxicam, aceclofenac. Each drug was given to every patient for three months following a randomized order of administration. Serum levels of MMP-1, MMP-3, MMP-8 and TIMP-1, and ratios MMP-1/TIMP-1, MMP-3/TIMP-1, MMP-8/TIMP-1 were measured before and after treatment. RESULTS: The use of aceclofenac resulted in no significant variation in either MMPs concentration and MMPs/TIMP-1 ratio. This outcome concerns the three groups and the 36 patients that form them. After all patients had received all three NSAIDs, MMPs and TIMP-1, these parameters were compared to their initial and final median values. A significant reduction in MMP-3 was found so in all OA patients as in the group of knee OA patients. CONCLUSIONS: 1. Of the MMPs studied, MMP-3 levels were found to be significantly reduced after NSAIDs treatment. Therefore, serum MMP-3 levels in OA patients could be proven to be a useful evaluating marker of treatment on the cartilage level. 2. No significant differences were observed among NSAIDs administered with regards to their effect on MMPs and TIMP-1 concentration.