P18: Relationship between osteoid formations and iron deposition induced by chronic cadmium exposure in ovariectomized rats

Itai-Itai disease (IID) like osteomalacia is induced by long-term administration of cadmium (Cd) in rat; however the pathological mechanism is still unclear. Hiratsuka et al. reported that iron deposition was observed in the calcification front of bone in Cd administered rats, and suspected that the iron deposition was relevant to osteomalacia induced by Cd. In the present study, we investigated the relationship between iron deposition and osteoid tissue to resolve the pathogenesis of Cd induced osteomalacia. A total of 42 ovariectomized Sprague-Dawley rats were obtained at 7 weeks of age. CdCl 2 (0.5 mg/kg) was injected into the tail vein 5 days per week for 70 weeks. Erythropoietin (EPO) (100 IU/kg) or saline was also injected into subcutis once a week from 26 or 50 to 70 weeks. Rats were euthanized at 50 or 70 weeks, and all organs were collected systemically. The right femora were fixed in 10% neutral-buffered formalin and decalcified for HE stain. The left femora were fixed in 70% alcohol and undecalcified for Villanueva bone stain and Berlin blue stain. The Cd-induced changes, hypertrophy/hyperplasia of osteoclast, fibrous ostitis, hyperplasia of trabecular bone and dilatation of Haversian canal, were observed in HE stained femur at 50 weeks. These changes increased in severity at 70 weeks and were not influenced by EPO. The osteoid tissue increase by Cd was observed in Villanueva bone stain of femur at 50 weeks, and increased in severity at 70 weeks. This osteoid formation induced by Cd was not influenced by EPO at 50 or 70 weeks. Cd-induced iron deposition at the mineralization front was observed in Berlin blue stain of femur at 50 weeks, and this change increased in severity at 70 weeks. Iron deposition was suppressed by EPO; no iron deposition was observed in EPO group at 50 or 70 weeks. These results indicate that iron deposition of the femur was suppressed by EPO because of high iron consumption due to increased hematopoiesis, and that the osteoid tissue increased regardless of iron deposition.