After an initial balance favoring collagen formation and mineralization, bone turnover markers return to pre-treatment levels during long-term TNF-α inhibition in patients with ankylosing spondylitis

Mark Siderius; Anneke Spoorenberg; Frans G M Kroese; Eveline van der Veer; Suzanne Arends

doi:10.1371/journal.pone.0283579

After an initial balance favoring collagen formation and mineralization, bone turnover markers return to pre-treatment levels during long-term TNF-α inhibition in patients with ankylosing spondylitis

PLoS One. 2023 Mar 24;18(3):e0283579. doi: 10.1371/journal.pone.0283579. eCollection 2023.

Authors

Mark Siderius¹, Anneke Spoorenberg¹, Frans G M Kroese¹, Eveline van der Veer², Suzanne Arends¹

Affiliations

¹ Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
² Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Abstract

Background: Bone turnover balance favors bone formation, especially mineralization, during the first 3 years of treatment with TNF-α inhibitors (TNFi). Our aim was to evaluate the course of serum bone turnover markers (BTM) and to investigate if facilitation of mineralization reflected by BTM BALP continues to increase during 6 years of TNFi treatment in patients with ankylosing spondylitis (AS) in daily clinical practice.

Methods: Included were outpatients from the University Medical Center Groningen (UMCG) participating in the Groningen Leeuwarden Axial SpA (GLAS) cohort who were treated with TNFi for at least 6 years. Serum markers of collagen resorption, bone regulation, collagen formation and facilitator of bone mineralization (sCTX, OC, PINP and BALP, respectively) were measured at baseline, 3 and 6 months, 1, 2, 4 and 6 years. Z-scores were calculated to correct for age and gender.

Results: 53 AS patients were eligible for analyses (66% male, mean age 39±11 years). Disease activity showed rapid and sustained improvement after start of TNFi. Evaluating BTM, sCTX did not significantly change during 6 years of treatment. OC was only significantly increased at 3 months compared to baseline, with median change in Z-score of +0.5. PINP significantly increased at 3 and 6 months and 2 years of treatment, with maximum median change in Z-score of +0.3. Interestingly, BALP was significantly increased at all time points up to and including 2 years of TNFi treatment, with maximum change in median Z-score of +1.2, and decreased thereafter.

Conclusion: In AS patients receiving long-term TNFi, bone turnover balance favored collagen formation and facilitation of mineralization during the first 2 years of treatment. Thereafter, at 4 and 6 years of follow-up, BTM Z-scores returned to pre-treatment levels.

Copyright: © 2023 Siderius et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Biomarkers
Bone Remodeling / physiology
Calcification, Physiologic
Female
Humans
Male
Middle Aged
Spondylitis, Ankylosing* / drug therapy
Tumor Necrosis Factor Inhibitors / therapeutic use
Tumor Necrosis Factor-alpha

Substances

Tumor Necrosis Factor-alpha
Biomarkers
Tumor Necrosis Factor Inhibitors

Grants and funding

M. Siderius: none declared; A. Spoorenberg: Grant/research support from Abbvie, Pfizer, UCB, consultant for Abbvie, Pfizer, MSD, UCB, and Novartis; E. van der Veer: none declared; F. Kroese: none declared; S. Arends: none declared. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.