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

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 postrituximab therapy, was analysed for biomarkers of bone turnover (procollagen type I amino-terminal propeptide [P1NP], osteocalcin, â-isomerised carboxy-terminal telopeptide of type 1 collagen [âCTX] and osteoprotegerin [OPG]). Results A significant decrease in bone resorptionwas observed 6 months after rituximab (median change âCTX .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 ىg/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 âCTX 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.