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Acute Effects of Glucocorticoid Treatment, TNFα or IL-6R Blockade on Bone Turnover Markers and Wnt Inhibitors in Early Rheumatoid Arthritis: A Pilot Study

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Abstract

Tumor Necrosis Factor (TNF)-α and Interleukin (IL)-6 play a fundamental role in bone loss in rheumatoid arthritis (RA), partly due to the inhibition of the Wnt canonical pathway. The aim of our study was to investigate the short-term effects of three different treatments on Wnt inhibitors (Dkk-1 and sclerostin) and on bone turnover markers (BTMs): N-propeptide of type I collagen (PINP) and C-terminal telopeptide of type I collagen (β-CTX-I). We performed a retrospective analysis of prospectively collected data. We enrolled women affected by early RA (< 12 months) with active disease (DAS28 ≥ 2.6) despite a 6-month treatment with methotrexate (10–15 mg/week), who then started certolizumab pegol, tocilizumab, or methyl-prednisolone (8 mg/daily). Patients were divided into three groups according to the treatment. Blood samples were collected at baseline, week 1, and week 4. We selected 14 patients treated with certolizumab pegol, 14 patients with tocilizumab, and 20 patients with methyl-prednisolone. No difference between any of the tested parameters was found at baseline. β-CTX-I, Dkk-1, and sclerostin decreased after 1 week of treatment with certolizumab pegol (− 27% ± 21.5, − 50% ± 13.2, and − 30% ± 30.4, respectively, p < 0.05). Methyl-prednisolone induced similar changes, albeit less marked, on β-CTX-I and Wnt inhibitors, with a decrease in PINP (− 16.1% ± 16.5, p < 0.05). Tocilizumab did not significantly affect BTMs or Wnt inhibitors. No significant changes were found for PTH and 25OHD. In the first four weeks of treatment, TNFα inhibition showed strong effects on BTMs and Wnt inhibitors, differently from IL-6 blockade. Glucocorticoids induced similar changes; nonetheless, they showed undesired effects on bone formation.

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Acknowledgements

The authors would like to thank the LURM (Laboratorio Universitario di Ricerca Medica) Research Center, University of Verona, and especially Eliana Amato for performing the biochemical analyses.

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Authors and Affiliations

  1. Rheumatology Unit, University of Verona, Verona, Italy

    Angelo Fassio, Giovanni Adami, Alessandro Giollo, Ombretta Viapiana, Luca Idolazzi, Maurizio Rossini & Davide Gatti

  2. Rheumatology Unit, AOU of Bologna, Policlinico S. Orsola Malpighi, Department Cardio-Toraco-Vascolare Alma Mater Studiorum, Bologna, Italy

    Nazzarena Malavolta

  3. Rheumatology and Rehabilitation Unit, Salvatore Maugeri Foundation IRCCS, Castel Goffredo, Mantua, Italy

    Gianantonio Saviola

  4. Rheumatology Unit, S. Chiara Hospital, Trento, Italy

    Roberto Bortolotti

  5. Unit of Internal Medicine, Department of Medicine, University of Verona, Verona, Italy

    Francesco Bertoldo

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  1. Angelo Fassio
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Correspondence to Angelo Fassio.

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Human and Animal Rights and Informed Consent

The study was conducted according to the protocol 1483CESC approved by our local Ethics Committee, in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from all individual participants included.

Conflict of interest

Maurizio Rossini reports personal fees from AbbVie, Abiogen, Eli-Lilly, Merck Sharp & Dohme, Novartis, Sanofi, UCB, outside the submitted work. Angelo Fassio, Giovanni Adami, Alessandro Giollo, Ombretta Viapiana, Nazzarena Malavolta, Gianantonio Saviola, Roberto Bortolotti, Luca Idolazzi, Francesco Bertoldo and Davide Gatti have no conflict of interest to declare.

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Fassio, A., Adami, G., Giollo, A. et al. Acute Effects of Glucocorticoid Treatment, TNFα or IL-6R Blockade on Bone Turnover Markers and Wnt Inhibitors in Early Rheumatoid Arthritis: A Pilot Study. Calcif Tissue Int 106, 371–377 (2020). https://doi.org/10.1007/s00223-019-00649-3

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