Experimental Reproduction of itai-itai disease in cynomolgus monkeys

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Itai-Itai means ouch-ouch in English, and human patients affected with the Itai-Itai disease (IID) complain of severe and continuous pain caused by spontaneous, multiple fractures of bones. IID occurs mainly in post-menopausal women and characteristic pathological findings of the disease are tubular nephropathy, osteomalacia and renal anemia. Many workers have tried to reproduce the bone lesion and renal anemia by Cd intoxication using various animals, but few of them succeeded in producing osteomalacia. Renal anemia has not been observed in Cd-treated animals. Because of the difficulties in the experimental reproduction of the lesions distinctive of IID by Cd treatment, some researchers insist that the real cause of IID is not Cd toxicosis, but malnutrition or vitamin D deficiency. Paucity of animal model of IID has also impeded the better understanding of the pathogenesis of tubular nephropathy, renal anemia and osteomalacia of IID, development of novel treatment for the disease, and establish more reasonable criteria for the diagnosis of the disease.In the present our experiment, ten, ovariectomized cynomolgus monkeys were given intravenous injections of 0, 1.0 or 2.5 mg/kg Cd, 2 or 3 days per week, for 13 to 15 months. Normocytic normochromic anemia, renal lesions characterized by tubular atrophy and interstitial fibrosis (Cd nephropathy) and bone lesions characterized by the increase of osteoid and osteopenia (Cd osteopathy) were induced in the monkeys treated with Cd.Our experiment demonstrated that the chronic cadmium toxicosis similar to IID of humans is reproducible in monkeys by repeated intravenous injection of Cd. Using these animal models, we are now developing novel therapy for IID.