Effect of Tocilizumab on Bone Outcomes in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-analysis

Background Tocilizumab (TCZ), an interleukin-6 receptor inhibitor for rheumatoid arthritis (RA), may benefit bone metabolism. This meta-analysis aimed to synthesize the effects of TCZ on bone turnover markers (BTMs) and bone mineral density (BMD). Methods Cochrane Library, Embase, PubMed, Scopus, and Web of Science were searched from inception to 23 February 2025. Randomized controlled trials and observational studies comparing TCZ with controls and reporting BTMs or BMD were included. Pooled mean differences (MDs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. Results Eight studies involving 1,221 participants were included. TCZ significantly reduced C-terminal telopeptide of type I collagen (CTX-I) (MD = -0.05, 95% CI [-0.08, -0.02], P = 0.001; I2 = 0%) and carboxyterminal telopeptide of type I collagen (ICTP) (MD = -7.19, 95% CI [-12.39, -1.99], P = 0.007; I2 = 97%), and increased procollagen type I N-terminal propeptide (PINP) (SMD = 0.21, 95% CI [0.08, 0.34], P = 0.001; I2 = 0%). The overall effect on osteocalcin (OC) was not significant, whereas RCT subgroup analysis showed a significant increase (MD = 3.83, 95% CI [1.12, 6.54], P = 0.006). No significant improvement in femoral neck BMD or lumbar spine BMD was observed. Conclusions TCZ may improve bone metabolism in RA by suppressing bone resorption and promoting bone formation. However, these biochemical changes did not translate into measurable increases in BMD during follow-up. Further long-term studies are warranted to clarify effects on BMD.