Iron deposition at mineralization fronts and osteoid formation following chronic cadmium exposure in ovariectomized rats.

To investigate whether chronic exposure of cadmium (Cd) chloride induces osteomalacic lesions similar to Itai-itai disease (IID), ovariectomized rats were injected intravenously with the cadmium at doses of 0.05 and 0.5 mg/kg/day, 5 days per week, for 50 weeks. In six rats in the 0.5 mg/kg group, the administration was continued for up to 70 weeks. In the 0.5 mg/kg group, the plasma concentration of calcium was similar in the treatment and control groups throughout the treatment period. The urinary excretion of calcium increased from 20 weeks and the increase became marked from 40 weeks. Histopathologically, osteoid seams in the femur, tibia, and humerus were increased from 50 weeks, and these changes became prominent at 70 weeks. Hypertrophy and hyperplasia of chief cells in the parathyroid were also observed from 50 weeks. The osteoid morphometry of the trabecular bone of the femur and sternum revealed a dose-dependent increase in osteoid/bone volumes. Roentgenographs of the antebrachial and metacarpal bones taken at 70 weeks showed so-called paper bone. The bone Cd content markedly increased until 25 weeks, but thereafter decreased linearly for up to 70 weeks. In contrast to the Cd content, the iron content decreased until 25 weeks, but thereafter increased until 70 weeks. Undecalcified section of the humerus showed the deposition of iron and formation of osteoid at mineralization fronts. Our data suggest that osteomalacic lesions were caused by chronic Cd intoxication, and that iron, as well as Cd, was involved in osteoid formation.