Erschienen in:
01.12.2011 | Original Article
Suppression of bone turnover by B-cell depletion in patients with rheumatoid arthritis
verfasst von:
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
Erschienen in:
Osteoporosis International
|
Ausgabe 12/2011
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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.