EFFECT OF CLODRONATE ON ESTABLISHED ADJUVANT ARTHRITIS

The rat adjuvant arthritis model was used to study the effect of disod ium clodronate on inflammation and destruction of tarsal bones and joi nts. Male Lewis rats were given an intradermal injection of mycobacter ia. Fourteen days after immunization, rats with similar scores were as signed to the different experimental groups. They were treated subcuta neously either with saline (controls) or with clodronate at doses of 1 2.5 and 25 mg/kg/day five times a week for 2 weeks. Clinical signs of arthritis including the severity of paw swelling were assessed weekly. At the time of sacrifice, histological features of the non-decalcifie d tarsus with ankle, intertarsal and tarsometatarsal joints were asses sed for inflammatory soft-tissue, articular and bone changes. The tota l histological score of the hindpaw indicated that 58% of the control rats developed moderate arthritis and 42%, severe arthritis. The treat ment with clodronate (25 mg/kg) decreased clinical signs of arthritis and the activity of the collagen-degrading lysosomal enzyme, beta-N-ac etylglucosaminidase, in inflamed hindpaw tissue. Histological evaluati on indicated moderate arthritis in 83%, but no severe arthritis. The l ower dose of clodronate also decreased the severity of the disease; th e decrease was, however, statistically insignificant. The results show that clodronate given therapeutically to adjuvant arthritic rats supp resses the intensity of the inflammation and prevents secondary articu lar and bone lesions in the tibiotarsal region.