Osteoporosis International

, Volume 22, Issue 12, pp 3067–3072 | Cite as

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

  • G. Wheater
  • V. E. Hogan
  • Y. K. O. Teng
  • J. Tekstra
  • F. P. Lafeber
  • T. W. J. Huizinga
  • J. W. J. Bijlsma
  • R. M. Francis
  • S. P. Tuck
  • H. K. Datta
  • J. M. van Laar
Original Article

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 (rs = 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.

Keywords

B cell Bone turnover Inflammation Osteoclastogenesis Osteoporosis Rheumatoid arthritis 

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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2011

Authors and Affiliations

  • G. Wheater
    • 1
  • V. E. Hogan
    • 2
  • Y. K. O. Teng
    • 3
  • J. Tekstra
    • 4
  • F. P. Lafeber
    • 4
  • T. W. J. Huizinga
    • 3
  • J. W. J. Bijlsma
    • 4
  • R. M. Francis
    • 5
  • S. P. Tuck
    • 6
  • H. K. Datta
    • 2
  • J. M. van Laar
    • 2
    • 6
  1. 1.Department of BiochemistryThe James Cook University HospitalMiddlesbroughUK
  2. 2.Musculoskeletal Research Group, Institute of Cellular MedicineNewcastle UniversityNewcastle upon TyneUK
  3. 3.Department of RheumatologyLeiden University Medical CentreLeidenThe Netherlands
  4. 4.Department of Rheumatology and Clinical ImmunologyUniversity Medical Centre UtrechtUtrechtThe Netherlands
  5. 5.Institute for Ageing and HealthNewcastle UniversityNewcastle upon TyneUK
  6. 6.Department of RheumatologyThe James Cook University HospitalMiddlesbroughUK

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