Effect of cyclical intermittent etidronate therapy on circulating osteoprotegerin levels in patients with rheumatoid arthritis

Abstract

Objective: To evaluate the role of serum osteoprotegerin (OPG) as a biochemical marker for disease activity assessment and drug monitoring in patients with rheumatoid arthritis (RA) treated with cyclical etidronate. Design: Forty patients (35 women and 5 men) with RA of < 5 years duration were randomized to receive intermittent cyclical etidronate therapy in conjunction with anti-rheumatic therapy or anti-rheumatic therapy alone (without etidronate) in a 2-year, open-label protocol. Methods: Radiographs of hands and feet and serum samples for the determination of OPG, amino terminal propeptide (PINP), cross-linked C-telopeptide (ICTP) and amino terminal telopeptid of type I collagen were obtained at baseline and at 24 months. Results: Etidronate treatment had no effect on circulating OPG levels, although the significant decline in PINP and ICTP (P = 0.001 and P = 0.04 respectively) reflected the efficacy of the anti-resorptive therapy. At baseline and at study termination, serum OPG correlated significantly with age (r = 0.45; P = 0.003 and r = 0.56; P = 0.0002 respectively). OPG was not related to biochemical markers of bone metabolism, indices of disease activity or radiographic disease progression. At baseline, the mean serum OPG was higher in patients receiving 5-10 mg/day prednisone (82.8±4.0 pg/ml, n = 16) compared with those receiving < 5 mg/day or with no prednisone (69.7±4.7 pg/ml, n = 23) (P = 0.05). Conclusions: Our results suggested that serum OPG measurement, perhaps because of the complexity of the regulation of the OPG, may be difficult to utilize in the evaluation of anti-resorptive therapy. Moreover, low dose corticosteroid-associated osteoporosis is probably not mediated by inhibition of OPG.