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Suppression of bone turnover by B-cell depletion in patients with rheumatoid arthritis

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Abstract

Summary

The role of B cells in inflammatory bone formation and resorption is controversial. We investigated this in patients with rheumatoid arthritis (RA) treated with rituximab, a B-cell depleting antibody. We found a significant suppression in bone turnover, possibly a direct effect or as a consequence of a reduction in inflammation and disease activity.

Introduction

RA is the most prevalent inflammatory joint disease, in which B cells play an important role. However, the role of B cells in bone turnover is controversial and RA subjects treated with rituximab, a B-cell depleting monoclonal antibody, provide an ideal model for determining the role of B cells in inflammatory bone resorption.

Methods

Serum from 46 RA patients, collected pre- and post-rituximab therapy, was analysed for biomarkers of bone turnover (procollagen type I amino-terminal propeptide [P1NP], osteocalcin, β-isomerised carboxy-terminal telopeptide of type 1 collagen [βCTX] and osteoprotegerin [OPG]).

Results

A significant decrease in bone resorption was observed 6 months after rituximab (median change βCTX −50 ng/L, 95%CI −136, −8 p < 0.001, this equates to −37%; 95%CI −6, −49), mirrored by a reduction in disease activity. Similarly, there was a significant increase in P1NP, a marker of bone formation (median change P1NP 5.0 μg/L, 95%CI −1.0, 11.2, p = 0.02; 13%; 95%CI −3, 39), but no significant change in osteocalcin or OPG levels. The percentage change from baseline of βCTX in a subgroup of patients (not on prednisolone or bisphosphonate) was significantly correlated with the percentage reduction in DAS28 score (r s = 0.570, p = 0.014).

Conclusions

In conclusion, we have found that B-cell depletion increases bone formation and decreases bone resorption in RA patients; this may be a direct effect on osteoblasts and osteoclasts, respectively, and be at least partially explained by the decreased inflammation and disease activity.

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Acknowledgements

The authors wish to thank the patients, investigators and study personnel in The Netherlands who made the rituximab trial possible. We acknowledge Nivine Levarht for preparing and arranging shipment of the samples. The study was supported by a research grant from the R&D department at The James Cook University Hospital, Middlesbrough. (Reference number 2008006) and the JGW Patterson Foundation, Newcastle upon Tyne.

Conflicts of interest

JMvL and JWJB have received a research grant, consultancy and speaker fees from Roche. TWJH has received lecture fees/consultancy fees from Schering Plough, Bristol Myers Squibb, Biotest AG, Wyeth/Pfizer, Novartis, Roche, Sanofi-Aventis, Abbott and Axis-Shield diagnostics and support for travelling to EULAR/ACR meetings from Roche & Abbott. SPT has received speaker fees from Ely Lilly. Roche is not financing this manuscript.

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Correspondence to G. Wheater.

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Wheater, G., Hogan, V.E., Teng, Y.K.O. et al. Suppression of bone turnover by B-cell depletion in patients with rheumatoid arthritis. Osteoporos Int 22, 3067–3072 (2011). https://doi.org/10.1007/s00198-011-1607-0

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  • DOI: https://doi.org/10.1007/s00198-011-1607-0

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