Combined effects of infliximab and methotrexate on rheumatoid arthritis osteoblastic cell metabolism.

The goal of this study is to investigate the in vitro effects of two disease-modifying anti-rheumatic drugs, largely used in the treatment of rheumatoid arthritis (RA), [infliximab (IFX) and methotrexate (MTX)], in RA primary osteoblast cell cultures. MTX inhibited proliferation and metabolic activity in RA osteoblasts was able to increase apoptosis. Conversely, IFX increased the proliferation, osteocalcin production and the alkaline phosphatase activity. Interestingly, IFX appeared to antagonise the negative effect exerted by MTX. Both drugs significantly reduced the IL-6 production in osteoblasts when used alone, and the combination of the two agents resulted in a significant additional reduction of IL-6 synthesis, with an apparent additive effect. The present study suggests that MTX exerts negative direct effects on bone metabolism in RA patients, but the combined treatment with anti-TNF-α can be beneficial for the interaction of MTX with bone cells.