However, our patients experienced a longer disease duration and lower baseline T-scores. 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 experienced lower lumbar spine and femoral neck T-scores. After 2-12 months TCZ treatment, CTX levels significantly decreased (0.32 0.21 vs. 0.26 0.17, = 0.038). Femoral neck BMD increased significantly (0.71 0.22 vs. 0.69 0.55, = 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 CHDI-390576 bone resorption and increased femoral BMD in ACPA-positive patients. The net effects of glucocorticoids and IL-6 inhibition on BMD imply that rigid inflammation control might affect bone metabolism. Introduction Rheumatoid arthritis (RA) is associated with increased systemic bone loss, resulting in a high risk of hip and vertebral fractures [1C3]. CHDI-390576 Concomitant glucocorticoid treatment and chronic systemic inflammation contribute Rabbit polyclonal to ERMAP to the increased risk of osteoporosis [4,5]. Tumour necrosis factor (TNF)- and interleukin (IL)-6 are key cytokines involved in RA pathogenesis and bone complications [6]. In the past 15 years, biological therapies targeting TNF- were associated with reduced bone destruction and reduced systemic bone loss [7]. After TNF- inhibition, the bone formation marker N-terminal propeptide of type I procollagen (PINP) increased, whereas the bone resorption marker C-terminal crosslinking telopeptide of type I collagen (CTX) decreased [7]. However, the effects of TNF- blockers around the incidence of fracture remain unclear. Epidemiological studies have not reported any difference in nonvertebral fractures with the use of TNF- antagonists [8,9]. IL-6 promotes systemic bone resorption by regulating osteoclast activation and differentiation [10]. Serum IL-6 levels were negatively correlated with the T-scores of the spine and hip in RA [11]. Tocilizumab (TCZ), an IL-6 receptor inhibitor, could effectively control systemic inflammation and reduce radiographic damage [12]. CTX decreased significantly after TCZ therapy, indicating that IL-6 inhibition reduces bone resorption [13]. Moreover, TCZ was revealed to increase bone mineral density (BMD) in patients with active RA and baseline osteopenia [14]. However, a contradictory result of no switch in BMD after 48 weeks of TCZ treatment was reported [15]. Therefore, the effects of TCZ treatment on BMD remain unclear. Several impartial studies have indicated an association of anticitrullinated protein antibody (ACPA) positivity in RA with radiographic progression [16, 17]. ACPA levels were also associated with CTX in patients with RA [18]. In addition, ACPA directly induces bone loss by binding to osteoclast surfaces, leading to bone resorptive activities [18]. Recent studies have also exhibited that ACPA titers were inversely associated with BMD in CHDI-390576 early and established RA cohorts [19C21]. Rheumatoid factor (RF) and ACPA positivity could predict the therapeutic responses of rituximab and abatacept, but not of TCZ [22]. However, the effects of ACPA positivity and changes in BMD after TCZ treatment have not yet been explored. The purpose of the current study was to investigate the differential effects of ACPAs on bone turnover markers (BTMs) and changes in BMD after 2-12 months TCZ treatment in patients with RA. Materials and methods Study participants CHDI-390576 In this study, 76 patients with RA followed at Taichung Veterans General Hospital, Taiwan, between March 2013 and May 2016 were recruited. All patients fulfilled the 2010 ACR and EULAR classification criteria for RA [23]. Enrolled patients were inadequate responders to at least two combinations of an adequate dose of methotrexate (MTX)-based conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), previous biological disease-modifying antirheumatic drugs (bDMARDs), or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs). This study was approved by the Ethics Committee of Clinical Research, Taichung Veterans General Hospital (CG16070A)..