Effect of chronic low-level cadmium intoxication on the haversian remodeling system in dogs: A reversible phenomenon

Summary

Four skeletally mature male littermate standardized research Beagles were exposed to differing concentrations of cadmium chloride in their drinking water in order to study the effects of this exposure on haversian bone remodeling activity. For approximately 6-month periods the dogs were exposed to 25 ppm, 10 ppm, and less than 1 ppb, respectively, in a sequential manner. After suitable fluorescent labeling, a biopsy was performed from the mid-shaft of a rib before the exposure to cadmium and at the end of each exposure period. Biochemical and hematologic results of all dogs monitored at monthly intervals showed no significant changes during the experimental periods nor did they differ significantly from untreated control Beagles. Plasma levels of immunoreactive parathyroid hormone and of 1,25-dihydroxycholecalciferol did not vary when measured at the end of the experimental periods, nor did they vary significantly from those of untreated control Beagles. Tissue levels of cadmium were measured in liver, kidney, and bone. Statistically significant differences in haversian bone remodeling measurements were observed between experimental and untreated control animals in activation frequency, radial closure rates, number of osteoid seams per mm², and bone formation rates when the experimental animals were exposed to 25 ppm cadmium chloride. These differences tended to disappear at the end of the 10 ppm exposure period and disappeared completely when the experimental animals were given ordinary tap water. The results suggest that the effect of cadmium on haversian bone remodeling is not related to mechanisms mediated through interference with parathyroid hormone activity or the metabolism of vitamin D, that the effect may represent a toxic effect at the cell level in bone, and that this effect is reversible.