The effects of calcitonin and colchicine on the cellular response to diphosphonate

Abstract

The mechanism by which diphosphonates inhibit bone resorption remains speculative; however, the osteoclast appears to be selectively affected by the drug. This study examined the effects off diphosphonate on osteoclasis in bones treated concomitantly with agents which reduce the osteoclast ruffled border, calcitonin and colchicine. Dichloromethylene diphosphonate, calcitonin, and colchicine inhibited parathyroid-hormone-stimulated bone resorption, as indicated by a significantly reduced release of 45Ca from prelabelled long bones. Quantitative and qualitative histological analyses of osteoclasts indicated differences among effects resulting from agents. Only bones treated with diphosphonate demonstrated a majority of osteoclasts with degenerative appearance; colchicine-treated bones exhibited many spherulated cells with cytoplasmic blebs. The number of normal osteoclasts in calcitonin-treated bones was the same as in controls and decreased with diphosphonate and colchicine treatment. All inhibitory agents reduced the number of nuclei per osteoclast; furthermore, colchicine effected an additional significant reduction, as compared with diphosphonate and calcitonin. The number and frequency of abnormal osteoclasts was increased by diphosphonate, but unaffected by colchicine and calcitonin. The addition of calcitonin, but not colchicine, to diphosphonate-treated bones decreased the incidence of abnormal osteoclasts. Although both calcitonin and colchicine are known to reduce the osteoclast ruffled border, this study has shown differences between the morphological effects of the 2 agents which presumably reflect differences in their mode of action and their interaction with diphosphonate.