Micro-CT imaging analysis for the effect of celecoxib, a cyclooxygenase-2 inhibitor, on inflammatory bone destruction in adjuvant arthritis rats

Abstract

Cyclooxygenase (COX)-2 is known to play an important role in the differentiation and maturation of osteoclasts. However, the role of COX-1 in bone metabolism has not been well explored. In this study, the bone-conserving effects of COX-2-specific (celecoxib), COX-nonselective (loxoprofen), and COX-1-specific agents (SC-58560) were compared using an adjuvant-induced arthritis (AIA) rat model. Arthritis was induced by injecting 50 microl liquid paraffin containing 1 mg Mycobacterium butyricum into the left footpad of Lewis rats. Drugs were given orally twice daily for 10 days beginning 15 days after adjuvant injection. Celecoxib was administered at the rate of 3 mg/kg per day, loxoprofen at 3 mg/kg per day, and SC-58560 at 10 mg/kg per day. The therapeutic effects on 3-D architectural bone changes in the arthritic condition, e.g., the bone volume/total tissue volume ratio and the amount of trabecular bone pattern factor, were determined by analyzing the hindpaw calcaneus of AIA rats using microcomputed tomography (micro-CT). In addition, dual-energy X-ray absorptiometry 2-D bone analysis was performed to compare with micro-CT analysis. AIA rats are prone to substantial bone erosion, which allows for significant changes in the 3-D architectural index. This inflammatory bone destruction was suppressed potently by celecoxib, only moderately by loxoprofen, and not at all by SC-58560. These data suggest that COX-2 plays an important role in the inflammatory bone destruction that occurs with rheumatoid arthritis. The results also suggest that COX-2 is more effective than COX-1 at suppressing the destruction of bone associated with arthritis.