The effect of 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (ADP) on the resorptive function of osteoclasts of known nuclear number.

Abstract

Bisphosphonates (BP) are known to suppress osteoclastic resorption in vivo and in vitro, but doubt persists as to how, and the effect of BP on the resorptive capability of osteoclasts of known nuclear number is unknown. We aimed to find whether the addition of 3-amino-1-hydroxypropylidene-1,1- bisphosphonate (APD) changed the nuclear profile of an osteoclast population in vitro, and to measure the resorptive efficiency of individually characterized osteoclasts in the presence and absence of the BP. Prehatch chick bone cells were cultured for 24 hours on slices of dentine in medium with or without added APD at 10(-6) M or 10(-8) M, or in control medium on dentine presoaked with 10(-6) M APD for 48 hours. Total pit counts, and pit depths, areas and volumes for pits made by osteoclasts of known nuclear number, were found using confocal video-rate laser reflection microscopy and 3-D image analysis software. APD in the medium inhibited resorption and reduced the volume, area, and depth resorbed per nucleus per chick osteoclast. The nuclear number distribution did not shift significantly, suggesting that no preferential effect arose from the APD affecting one size of cell more than another. The large reduction found in pit numbers, depths, areas, and volumes in the APD dentine-pretreated group supports previous views that BP released during resorption act as metabolic inhibitors, altering protein synthesis by the cell. Larger cells made larger pits, but resorptive efficiency was similar for different cell sizes within the control or APD-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)