SLOW-RELEASE CLODRONATE IN PREVENTION OF INFLAMMATION AND BONE LOSS ASSOCIATED WITH ADJUVANT ARTHRITIS

The effects of slow-release calcium clodronate on rat adjuvant arthrit is were investigated using two different dosing schedules. In prophyla ctic treatment, calcium clodronate was given on the same day as the ad juvant injection, and in therapeutic treatment, calcium clodronate adm inistration was delayed until the animals had active disease, to day 1 4 postadjuvant. Calcium clodronate was given as single i.m. injections into the thigh muscles. Arthritis index, histopathology of hindpaw, q uantitative histomorphometry, bone mineral density and serum osteocalc in, alkaline phosphatase and calcium were studied. Calcium clodronate given therapeutically decreased the severity of paw swelling slightly more than prophylactic treatment, a result seen as lower scores of art hritis index. Histopathological evaluation of hindpaws showed that cal cium clodronate protected against inflammation-induced bone loss and r eactive bone formation in the hindpaw, but not against inflammatory ch anges involving articular cartilage. Quantitative histomorphometric an alysis of the distal femur indicated that trabecular bone area was dec reased by 86% in arthritic rats compared with normal untreated control s. Both the prophylactic and the therapeutic treatment with calcium cl odronate prevented this osteopenia (P < .001). Bone mineral density me asured by computed tomography was also significantly reduced in distal femoral metaphysis in adjuvant arthritic rats, but restoration to vir tually normal values occurred with calcium clodronate (P < .001). In b oth dosing schedules, we observed a suppression of arthritis, which wa s associated with a decrease in paw swelling and an inhibition of the severe osteopenia in the distal femoral metaphysis. The long duration of action after a single injection of calcium clodronate indicates tha t the insoluble salt remains at the injection site and is released slo wly into the bloodstream.