Tocilizumab potentially prevents bone loss in patients with anticitrullinated protein antibody-positive rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is associated with a high risk of osteoporosis and fracture. Interleukin (IL)-6 inhibitors may suppress osteoclast activation. Anticitrullinated protein antibody (ACPA) titers are inversely associated with bone mineral density (BMD). However, the differential effect of ACPA on bone turnover marker (BTM) and BMD changes after IL-6 inhibition remains unclear. This prospective study recruited patients with active RA with inadequate response to methotrexate or biologics. BMD was measured before and after 2-year tocilizumab (TCZ) treatment. Serum osteocalcin, N-terminal propeptide of type I collagen (P1NP), and C-terminal cross-linking telopeptide of type I collagen (CTX) levels were assessed at the baseline and after treatment. We enrolled 76 patients with RA (89.5% women, age: 57.2 ± 13.3 years) receiving TCZ. The 28-joint disease activity score was negatively correlated with BMD and T-scores of the lumbar spine and bilateral femoral neck. ACPA-positive patients had lower lumbar spine and femoral neck T-scores. After 2-year TCZ treatment, CTX levels significantly decreased (0.32 ± 0.21 vs. 0.26 ± 0.17, p = 0.038). Femoral neck BMD increased significantly (0.71 ± 0.22 vs. 0.69 ± 0.55, p = 0.008). Decreased CTX levels and improved BMD were observed only in ACPA-positive patients. After treatment, femoral neck BMD significantly increased only in patients receiving a glucocorticoid dose of ≥5 mg/day. Two-year TCZ treatment reduced bone resorption and increased femoral BMD in ACPA-positive patients. The net effects of glucocorticoids and IL-6 inhibition on BMD imply that strict inflammation control might affect bone metabolism.

Osteoporosis in Inflammatory Arthritides: New Perspective on Pathogenesis and Treatment

“…Indeed, they found that IL-6 blockade reduced bone erosion in TNF-α transgenic murine models through a direct effect on osteoclast activity which was independent from the anti-inflammatory action ( 61 ). Other studies on human subjects further confirmed the positive effect of tocilizumab on bone erosions ( 62 ) and systemic bone loss, especially in ACPA positive patients ( 52 , 63 ).…”

Tocilizumab Was Effective in Repairing the Large Geode in a Patient with Rheumatoid Arthritis

“…Kume et al showed the improvement effect on bone mineral density (BMD) in patients with RA treated with tocilizumab [ 23 ]. Furthermore, Chen et al showed the decrease of the bone resorption marker and BMD improvement with tocilizumab treatment [ 24 ]. These anti-bone resorption effects of tocilizumab may explain the repairing effect of the large geode.…”

Association between levels of synovial anti‐citrullinated peptide antibodies and neutrophil response in patients with rheumatoid arthritis

“…Additionally, IL‐6 is one of the key cytokine effectors of the tissue response in RA , also having important effects on the production of antibodies by B cells . It was showed that IL‐6 inhibition in ACPA‐seropositive patients reduced bone loss, demonstrating that IL‐6 have a negative impact on bone metabolism in the presence of ACPAs .…”