Vol. 280, Issue 2, 1051-1056, 1997

Distribution of Clodronate in the Bone of Adult Rats and Its Effects on Trabecular and Cortical Bone

T. Österman, T. Virtamo, K. Kippo, L. Laurén, I. Pasanen, R. Hannuniemi and R. Sellman

Biomedical Research Center, Leiras Oy, FIN-20101 Turku, Finland

Distribution of clodronate in cancellous and cortical bone of the femur and in cancellous bone of lumbar vertebrae in adult rats was examined by means of quantitative autoradiography. In addition, the effects of clodronate on cancellous and cortical bone were evaluated by bone histomorphometry. Six-month-old male rats were given a mixture of unlabeled and ¹⁴C-labeled disodium clodronate subcutaneously on 5 consecutive days at cumulative doses of 125 mg/50 µCi/kg or 250 mg/100 µCi/kg and followed up for 2, 23 or 79 days after the last dose. The highest activity of ¹⁴C-clodronate was found in the primary spongiosa of the distal femoral metaphysis and in the cortical bone of the femoral diaphysis. Radioactivity in the lumbar vertebra was found to be about half of that in the femur. No marked decrease in radioactivity was found in bone specimens taken after the follow-ups. In these specimens, however, labeled clodronate originally incorporated into the primary spongiosa was situated further away from the growth plate because of longitudinal bone growth. A cross-section of the femoral shaft showed that incorporation of clodronate was more prominent into the periosteal surface than into the endocortical surface. No marked histological effects were seen, except for an increase in the mineralized hard tissue area in the primary spongiosa of the distal femur.