Effect of dichloromethane diphosphonate on cortisol-induced bone loss in young adult rabbits

Cortisol, 2.5 mg/kg, dichloromethane diphosphonate (Cl2MDP), 0.1, 1.0 and 4.0 mg/kg, and combinations of the two were administered daily for 42 days to young adult rabbits (3.9 kg) to determine if Cl2MDP could inhibit development of cortisol-induced osteopenia. A beginning and a terminal control group were included in the experiment. In the terminal controls compared with the beginning controls, the proximal tibia lost cortical and trabecular bone, the distal femur gained cortical bone and the lumbar vertebral body lost trabecular bone. The administration of Cl2MDP alone inhibited bone resorption at those sites where bone loss was occurring. Two cortical bone sites showed gains in bone. The 1.0 mg/kg dose was most effective. In rabbits administered cortisol, bone formation was inhibited; the number of osteoclasts was markedly increased, cortical bone was lost in all the bones examined, and there was no marked effect on trabecular bone. Cl2MDP administered with cortisol partially inhibited cortisol-induced bone loss. The concomitant administration of Cl2MDP did not alter the number of osteoclasts and osteoblasts. The 1.0 mg/kg dose was most effective. The results of this study clearly demonstrated the need to evaluate several bones and different sites within individual bones if erroneous conclusions are to be avoided when studying agents that affect bone metabolism.