Combination therapy with dexamethasone and osteoprotegerin protects against arthritis-induced bone alterations in antigen-induced arthritis of the rat

To investigate the influence of a combined therapy consisting of dexamethasone and osteoprotegerin (OPG) on bone alterations and disease activity in antigen-induced arthritis (AIA) in the rat. AIA rats received dexamethasone (0.25 mg kg(-1) day(-1), i.p.), OPG (2.5 mg kg(-1) day(-1), i.p.), or a combination of both at regular intervals for 21 consecutive days. At the end of the treatment, bone structure was analyzed by histomorphometry. Primary spongiosa was measured using linear scanning. AIA led to significant periarticular and axial bone loss. Dexamethasone monotherapy substantially suppressed joint swelling without inhibiting bone loss of the secondary spongiosa, whereas OPG monotherapy showed no anti-inflammatory effect. Despite reduction of bone resorption, OPG did not inhibit AIA-induced bone loss. In contrast, the combination of dexamethasone and OPG not only produced an anti-inflammatory effect, but also resulted in inhibition of periarticular and axial bone loss. OPG increased trabecular number of the primary spongiosa whilst combination therapy led to an increase in both trabecular number and trabecular width. The principle of combining a glucocorticoid together with inhibition of the receptor activator of NF-kappaB ligand (RANKL) may be an effective bone-saving therapy in rheumatoid arthritis.