Tumor necrosis factor α inhibitors (TNFi) are the major class of biologic drug used for the treatment of Rheumatoid arthritis (RA). Their effects on inflammation and disease control are well established, but this is not true also for bone metabolism, especially for key factors as parathyroid hormone and Wnt pathway. Those two pathways are gaining importance in the pathogenesis RA bone damage, both systemic and local, but how the new treatment affects them is still largely unknown. We studied 54 RA patients who were starting an anti-TNFα treatment due to the failure of the conventional synthetic disease-modifying antirheumatic drugs. Serum levels of Wnt/βcatenin pathway inhibitors (Dickkopf-related protein 1, Dkk1, and Sclerostin), Parathyroid hormone (PTH), vitamin D, and bone turnover markers were measured at baseline in the morning after fasting and after 6 months of therapy. We found a significant percentage increase in serum PTH (+32 ± 55 %; p = 0.002) and a decrease in Dkk1 mean serum levels (−2.9 ± 12.1; p = 0.05). PTH percentage changes were positively correlated both with C-terminal telopeptide of type I collagen and Dkk1 percentage changes. Sclerostin serum levels showed no significant difference. TNFi treatment provokes in the short term a rise in PTH levels and a decrease in Dkk1 serum levels. The increase of PTH might promote bone resorption and blunt the normalization of Dkk1 serum levels in RA. Those data give a new insight into TNFi metabolic effects on bone and suggest new strategies to achieve better results in terms of prevention of bone erosions and osteoporosis with TNFi treatment in RA.
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This study was performed in part in the LURM (Laboratorio Universitario di Ricerca Medica) Research Center, the University of Verona. The authors would like to thank Prof. Silvano Adami who left us the love for research and truth and the laboratory teams, especially Caterina Fraccarollo, for performing the biochemical analyses
Compliance with Ethical Standards
Conflict of Interest
Adami Giovanni, Orsolini Giovanni, Adami Silvano, Viapiana Ombretta, Idolazzi Luca, Gatti Davide, and Rossini Maurizio have no conflict of interest to declare.
Human and Animal Rights and Informed Consent
The study was approved by the institutional review board of the Medical School of Verona and performed according to the Helsinki declaration. All patients provided written informed consent for their participation in the study.
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