IN-VITRO STUDY OF THE EFFECTS OF ANTI-RHEUMATOID DRUGS ON OSTEOBLASTS

Abstract

Methotrexate and Cox-2 inhibitors are thought to interfere with bone healing. There have been controversial results published in the literature. The effect of newer antirheumatoids (Leflunomide, Etanercept, Infliximab) has not been studied. The aim of this study was to find the in-vitro effect of methotrexate, newer anti-rheumatoids, steroids and cox-2 inhibitors on Osteoblasts. Osteoblasts were cultured from femoral heads obtained from young otherwise healthy patients undergoing total hip replacement. The cells were cultured using techniques that have been previously described. A computer aided design of experiment was used as a model for setting up the experiment on samples obtained from five patients. Normal therapeutic concentration of the various antirheumatoids was added alone and in combination to the media. The cell growth was estimated after two weeks using spectrophotometric technique using Roche Cell proliferation Kit. Multiple regression analysis was done to estimate the best predictor of the final result. Patient was found to be the most significant factor (p< 0.001) in predicting the ultimate response. Cox-2 inhibitor (Etoricoxib) was found to be the next best predictor (p=0.043). Etoricoxib in fact had a stimulatory effect (R=0.219) on the osteoblast growth, which was accentuated in the presence of other agents that varied amongst different patients. Different patients respond differently to the drugs. None of the antirheumatoids inhibit osteoblast proliferation and differentiation in-vitro. If osteoblastic activity is considered to be the primary factor responsible for bone healing, then an inhibition should not result in patients who are on these drugs.