High-dose clodronate therapy prevents joint destruction in chronic antigen-induced arthritis of the rat but inhibits bone formation at the axial skeleton

Objective: To investigate the effects of clodronate on clinical disease act ivity, inflammatory alterations and cartilage destruction, periarticular an d axial bone volume and bone turnover in chronic antigen-induced arthritis (AIA; day 28). Methods: Rats with AIA were treated with clodronate (5 mg/kg/day continuous ly; 20 mg/kg/day intermittently or high-dose with 300 mg/kg 3 hours after a rthritis induction +20 mg/kg/day continuously, respectively). Joint patholo gy was examined by histology. Bone volume and cellular turnover parameters of the right tibia head and the third lumbar vertebra were evaluated by his tomorphometry. The findings were compared with those of healthy controls, s ham-treated AIA and AIA treated continuously with 250 mu g/kg of dexamethas one. Results: All three therapy regimens with clodronate resulted in a significa nt reduction of joint swelling, histopathological inflammatory changes and cartilage destruction in comparison with sham-treated AIA. The antiinflamma tory effect of high-dose clodronate was comparable with dexamethasone. The intermittent administration of 20 mg/kg/day of clodronate completely preven ted periarticular bone loss by reduction of bone resorption without affecti ng bone formation at the periarticular and axial bone. Both continuous trea tment with 5 mg/kg/day of clodronate and high-dose clodronate therapy parti ally prevented periarticular bone loss and reduced parameters of bone forma tion at the axial bone to values below those of healthy controls. Conclusion: High-dose clodronate therapy exerts an excellent preventive eff ect on clinical disease activity and on joint destruction in AIA. However, continuous treatment with high doses of clodronate may result in a low turn over state of bone remodelling.