Effects of cadmium on osteoclast formation and activity in vitro.

Chronic exposure to cadmium has been linked to bone loss, low bone mass, and increased incidence of fracture. To determine if Cd could directly increase the formation of cells responsible for bone resorption, we cultured normal canine bone marrow cells containing the progenitor cells for osteoclasts. Cultures were evaluated for the number of multinucleate osteoclast-like cells (MNOCs) formed. Exposure to Cd (10-100 nM) increased the number of MNOCs formed over control values when cultured in the presence but not in the absence of a bone wafer. The MNOCs formed were functional, evidenced by pits excavated on the bone wafers included in the cultures. By 12 days, MNOCs formed in the presence of 50 nM Cd excavated significantly more pits and a greater pit area than did untreated MNOCs. By 14 days, the control values were similar to those of the Cd-exposed MNOCs, but pit formation was enhanced by Cd in that the ratio of pit complexes to single pits was increased twofold over that for untreated cultures. Mature osteoclasts, isolated from the long bones of rat neonates and cultured for 1-3 days on bone slices, provided a direct method to assess the effect of Cd on osteoclast activity. Exposure of osteoclast cultures to 100 nM Cd increased the number of osteoclasts present over that for untreated osteoclasts by a factor of 1.7 +/- 0.1, the number of pits excavated by 2.8 +/- 0.6, the area excavated by 3.2 +/- 0.8, and the area excavated per osteoclast by 1.8 +/- 0.4 (mean +/- SE; n = six experiments). These data suggest that Cd accelerates the differentiation of new osteoclasts from their progenitor cells and activates or increases the activity of mature osteoclasts.