The effect of newer anti-rheumatic drugs on osteogenic cell proliferation: an in-vitro study

BACKGROUND: Disease modifying anti-rheumatic drugs (DMARDs) may interfere with bone healing. Previous studies give conflicting advice regarding discontinuation of these drugs in the peri-operative setting. No consensus exists in current practice especially with the newer DMARDs such as Leflunomide, Etanercept, and Infliximab. The aim of this study was to assess the in-vitro effect of these drugs alone and in relevant clinical combinations on Osteoblast activity. METHODS: Osteoblasts were cultured from femoral heads obtained from five young otherwise healthy patients undergoing total hip replacement. The cells were cultured using techniques that have been previously described. A full factorial design was used to set up the experiment on samples obtained from the five donors. Normal therapeutic concentrations of the various DMARDs were added alone and in combination to the media. The cell proliferation was estimated after two weeks using spectrophotometric technique using Roche Cell proliferation Kit. Multilevel regression analysis was used to estimate which drugs or combination of drugs significantly affected cell proliferation. RESULTS: Infliximab and Leflunomide had an overall significant inhibitory effect (p < 0.05). Dexamethasone had a small stimulatory effect that was however strongly donor-dependent. The cox-2 inhibitor Etoricoxib was found to negate or increase the action of two other drugs (Leflunomide and Dexamethasone). Methotrexate and Etanercept had no discernable donor-dependant or donor-independent effect on osteoblast proliferation. CONCLUSION: Our study indicates that in-vitro osteoblast proliferation can be inhibited by the presence of certain DMARDs. Combinations of drugs had an influence and could negate the action of a drug on osteoblast proliferation. The response to drugs may be donor-dependent.