Effects of One-Year Tofacitinib Therapy on Bone Metabolism in Rheumatoid Arthritis

Janus kinase (JAK) inhibitors are used to treat rheumatoid arthritis (RA). We assessed the effects of tofacitinib on bone density and bone markers in association with clinical and laboratory parameters in RA. Tofacitinib stabilized bone density and resulted in a positive balance of bone turnover.INTRODUCTION:Janus kinase (JAK) inhibitors emerged as new therapeutic options in rheumatoid arthritis (RA). We have little information on how it affects areal and volumetric bone mineral density (BMD) and bone turnover markers. The aim of this study was to assess the effects of 1-year tofacitinib therapy on bone metabolism in RA.METHODS:Thirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib for 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF), and anti-cyclic citrullinated peptide (CCP) levels, as well as serum levels of sclerostin, osteocalcin (OC), P1NP, DKK-1, OPG, RANKL, and 25-hydroxy-vitamin D3. Areal and volumetric BMD were assessed by DXA and peripheral quantitative CT (QCT), respectively.RESULTS:Twenty-six patients (13 on each arm) completed the study. Tofacitinib was clinically effective by suppressing DAS28, CRP, and HAQ. This was accompanied by the attenuation of further bone loss. Tofacitinib therapy significantly increased OC, OPG, and vitamin D3, while decreased CTX levels (p < 0.05). Age and multiple bone markers (OC, CTX, P1NP, RANKL) inversely correlated with L2-4 and femoral neck BMD by DXA. CRP, DAS28, and RANKL inversely determined volumetric BMD by QCT. Age, CRP, anti-CCP, and DKK-1 influenced the effects of tofacitinib therapy on BMD changes.CONCLUSIONS:One-year tofacitinib treatment stabilized BMD in RA patients and resulted in a positive balance of bone turnover as indicated by bone biomarkers. Further studies are needed to evaluate the potential beneficial effects of JAK inhibitors on inflammatory bone loss.