DISTRIBUTION OF CLODRONATE IN THE BONE OF ADULT-RATS AND ITS EFFECTS ON TRABECULAR AND CORTICAL BONE

Distribution of clodronate in cancellous and cortical bone of the femu r and in cancellous bone of lumbar vertebrae in adult rats was examine d by means of quantitative autoradiography. In addition, the effects o f clodronate on cancellous and cortical bone were evaluated by bone hi stomorphometry. Six-month-old male rats were given a mixture of unlabe led and C-14-labeled disodium clodronate subcutaneously on 5 consecuti ve days at cumulative doses of 125 mg/50 mu Ci/kg or 250 mg/100 mu Ci/ kg and followed up for 2, 23 or 79 days after the last dose. The highe st activity of C-14-clodronate was found in the primary spongiosa of t he distal femoral metaphysis and in the cortical bone of the femoral d iaphysis. Radioactivity in the lumbar vertebra was found to be about h alf of that in the femur. No marked decrease in radioactivity was foun d in bone specimens taken after the follow-ups. In these specimens, ho wever, labeled clodronate originally incorporated into the primary spo ngiosa was situated further away from the growth plate because of long itudinal bone growth. A cross-section of the femoral shaft showed that incorporation of clodronate was more prominent into the periosteal su rface than into the endocortical surface. No marked histological effec ts were seen, except for an increase in the mineralized hard tissue ar ea in the primary spongiosa of the distal femur.