Circulating levels of osteoprotegerin and sRANKL and the effect of methotrexate in patients with rheumatoid arthritis

Abstract

Background: Receptor activator of nuclear factor κβ ligand (RANKL) and osteoprotegerin (OPG) are pivotal molecules involved in osteoclast activation and resorption. In RA, their alterations mediated through inflammatory cytokines are responsible for erosions and systemic bone loss. This study planned to look at the effect of methotrexate on circulating levels of OPG and RANKL in RA. Methods: Methotrexate-naive patients with active rheumatoid arthritis (RA) between 18 and 65 years of age were included. Controls were derived from voluntary healthy blood donors after written consent. All patients were started on methotrexate at 15 mg/week, increased by 5 mg every 4 weeks till maximum tolerated dose or 25 mg/week whichever was lower. Circulating plasma levels of OPG and RANKL were measured for cases (at baseline and 24 weeks) and controls (at baseline). Results: Fifty-one consecutive patients with RA and 57 controls were recruited. Circulating OPG (mean ± standard deviation) levels were higher in RA patients as compared to controls, 2879.6 ± 1037.9 and 2214.1 ± 705.3 pg/ml, respectively (P < 0.001). RANKL levels did not differ significantly between cases and controls. After treatment, circulating OPG levels fell significantly, from 2879.6 ± 1037.9 to 2059.8 ± 532.1 pg/ml (P < 0.001), however, no significant change in circulating RANKL levels. No difference was found in OPG and RANKL levels between patients with erosive and nonerosive disease. Conclusions: OPG levels are higher in RA patients and normalize in response to treatment with methotrexate. The initial higher levels of OPG may represent a compensatory mechanism to osteoclast activation; they normalize on reduction of disease activity.

Keywords

• Methotrexate
• osteoprotegerin
• receptor activator of nuclear factor κβ ligand
• rheumatoid arthritis