Background/Purpose: Wnt signaling is an important regulator of bone remodeling and it is involved in the pathogenesis of focal and systemic bone loss in Rheumatoid Arthritis (RA) patients. The aim of the present study is to investigate the short-term effects of three different anti-inflammatory therapies on Wnt inhibitors and bone turnover markers (BTMs) in patients with early RA.

Methods: We performed a retrospective analysis of prospectively collected data. We enrolled women affected by early RA (< 12 months) according to 2010 ACR/EULAR criteria who started treatment with certolizumab pegol (200 mg SC weekly), tocilizumab (162 mg SC weekly) or methyl-predinsolone (8 mg daily). Women enrolled in the study were required to have positive RF and/or positive ACPA and active disease (DAS28 ≥2.6) despite stable treatment with subcutaneous methotrexate (10-15 mg/week) for at least 6 months. Clinical parameters and blood samples were collected at baseline, week 1 and week 4.

Results: Data were obtained for 14 patients treated with certolizumab pegol, 14 patients treated with tocilizumab and 20 patients treated with methyl-prednisolone. Mean DAS28 at baseline was 4.0 ± 0.7 No difference in any of the tested parameters was found at baseline. The percent changes of the serum levels of bone turnover markers, Dkk-1 and sclerostin are reported in Figure 1. CTX-I, Dkk-1 and sclerostin decreased abruptly after 1 week of treatment with certolizumab pegol (-27% ± 21.5%, -50% ± 13.2% and -30% ± 30.4% respectively), and similar results were found after 4 weeks. Methyl-prednisolone induced comparable changes, albeit less evident, on CTX-I and Wnt inhibitors. We found an increase in PINP serum levels after treatment with anti-TNFα, while we observed a decrease with methyl-prednisolone. Tocilizumab did not significantly affect BTMs or Wnt inhibitors.

Conclusion: TNFα inhibition seems to have a strong and quick effect on BTMs and Wnt inhibitors, which was not observed with IL-6 blockade, at least in the short-term. Glucocorticoid treatment exerts similar, though less prominent, changes, potentially linked to the suppression of inflammation, nonetheless it still show some undesired effects on bone metabolism (ie, suppression of bone formation).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/acute-effects-of-il-6-blockade-tnf%ce%b1-inhibitor-or-glucocorticoids-on-bone-turnover-markers-and-wnt-inhibitors-in-early-rheumatoid-arthritis/