AB0557 Effects of tocilizumab on bone homeostasis and DICKKOPF-1 in rheumatoid arthritis. (23rd January 2014) - Kitano, M.
Abstract : Background: Tocilizumab (TCZ) is a humanized monoclonal anti-IL-6 receptor antibody. TCZ has demonstrated efficacy in moderate to severe active rheumatoid arthritis (RA) with inadequate clinical response to disease-modifying anti-rheumatic drugs (DMARD) or tumor necrosis factor (TNF) inhibitors. Moreover, it is reported that TCZ combined with MTX reduces systemic bone resorption in RA. Dickkopf (DKK)-1, an endogenous inhibitory factor in the canonical Wnt signaling pathway, plays an important role in osteoclastic bone resorption via regulation of receptor activator of NF-kappa B ligand (RANKL)-osteoprotegerin (OPG) balance in rheumatoid arthritis (RA). Recently, it was reported that circulating DKK-1 was correlated with bone erosion and inflammation in RA. Objectives: To investigate the effects of TCZ on biochemical markers of bone, serum RANKL, OPG, and DKK-1 in patients with active RA. Methods: Twenty-eight patients with active RA (20 females, 8 males; age 51.6±10.7 years; disease duration 13.0±13.6 years; DAS28-ESR 5.5±1.4) were started on treatment with TCZ 8mg/kg intravenously every 4 weeks. Eighteen patients had a history of TNF-antagonist therapy such as infliximab, etanercept, and, adalimumab. All patients had been treated with methotrexate, other DMARDs and prednisolone continued at the stable pretreatment doses during in this study. Circulating levels of osteocalcin, type I collagen cross-linked N-telopeptides (NTx), soluble RANKL (sRANKL), OPG, and DKK-1 were examined by ELISA at baseline and after12 weeks. Results: At 12 weeks after the treatment of TCZ, a disease activity reduced significantly from the baseline (DAS28-ESR 5.5±1.4 vs 3.0±1.4; p<0.01). Average of NTx, sRANKL, and DKK-1 levels at 12 weeks after the treatment of TCZ decreased significantly from the baseline (NTx: 19.20 nmol BCE/l vs 16.43 nmol BCE/l; p<0.01, sRANKL: 0.819 pmol/l vs 0.689 pmol/l; p<0.05, and DKK-1: 2536 pg/ml vs 2065 pg/ml; p<0.01, respectively). Average of osteocalcin levels at 12 weeks increased significantly from the baseline (5.31 ng/ml vs 5.67 ng/ml; p<0.05). Average of OPG levels did not change significantly. Conclusions: These findings suggest that TCZ therapy improves systemic bone metabolism in patient with active RA through the increase of bone formation markers and the decrease of bone degradation markers. Moreover, TCZ might be improved osteoclastic bone destruction in RA via the regulation of DKK-1 and RANKL expression. Disclosure of Interest: None Declared