Abstract
Aim: To examine the in vitro effects of several non-steroidal anti-inflammatory drugs (NSAIDs) on pro-inflammatory cytokines and PGE2 production by interface membrane from loose endoprosthesis of hip or knee arthroplasty. Since these factors are strongly implicated in the bone resorption process and aseptic prosthesis failure we hypothesize that the probable inhibition of their production by prophylactic administration of NSAIDs, will retard these processes.
Materials and Methods: Interface membranes were harvested from ten patients who were subjected to revision surgery for aseptic total hip or knee replacement loosening and cultured for 72h in the absence or presence of therapeutic dosages of each, of aceclofenac, piroxicam, tenoxicam and indomethacin. Paracetamol was used as neutral control. In conditioned media the levels of IL-6, IL-1 (3, TNF-a and PGE2 were determined by ELISA and the data were analyzed by the Student’s t-test (significance level p< 0.05).
Results: All the tested NSAIDs caused a statistically significant decrease on IL-6 and TNF-a levels, with aceclofenac and tenoxicam to be more effective (caused decrease in 7 out of 10 samples), while they had low or controversial effect on IL-1β production, except aceclofenac that seemed to augment the IL-1β levels (statistically significant increase in 5 out of 9 samples). Finally all the tested drugs, except paracetamol, caused a marked reduction (80–99%) of PGE2 levels.
Conclusions: The stimulatory effect of IL-6 and TNF-α in the osteoclastic bone resorption process is well established. Considering the above results, the tested IMSAIDs (especially aceclofenac and tenoxicam) reduce the in vitro production of these mediators by interface membranes. Hence, it is reasonable to propose that the prophylactic treatment with these drugs could delay the process of the aseptic loosening. However, in order to support this hypothesis, more experiments are required by which the effects of them on other factors implicated in the loosening process, such as metalloproteinases, will be examined.
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