期刊
OSTEOPOROSIS INTERNATIONAL
卷 22, 期 12, 页码 3067-3072出版社
SPRINGER LONDON LTD
DOI: 10.1007/s00198-011-1607-0
关键词
B cell; Bone turnover; Inflammation; Osteoclastogenesis; Osteoporosis; Rheumatoid arthritis
资金
- R&D department at The James Cook University Hospital, Middlesbrough [2008006]
- JGW Patterson Foundation, Newcastle upon Tyne
- Roche
- Schering Plough
- Bristol Myers Squibb
- Biotest AG
- Wyeth/Pfizer
- Novartis
- Sanofi-Aventis
- Abbott
- Axis-Shield diagnostics
- Ely Lilly
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, beta-isomerised carboxy-terminal telopeptide of type 1 collagen [beta CTX] and osteoprotegerin [OPG]). Results A significant decrease in bone resorption was observed 6 months after rituximab (median change beta CTX -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 mu g/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 beta CTX 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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