Pathogenesis of Osteomalacia in Itai-itai Disease

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  • Umemura Takashi
    Laboratory of Comparative Pathology, Hokkaido University Graduate School of Veterinary Medicine
  • Wako Yumi
    Kashima Laboratory of Mitsubishi Chemical Safety Institute Ltd.

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Itai-itai disease (IID) is the most severe form of chronic cadmium (Cd) intoxication of human. The patients of IID suffer from renal anemia, tubular nephropathy and osteopenic osteomalacia, and 90% of the patients are post-menopausal women. Many efforts have been paid for reproducing the bone lesions using various animal species, but the pathogenesis of them is still controversial and conflicting among the reports. Two hypotheses have been proposed for the pathogenesis of the bone lesion: direct and indirect effects of Cd on bone. The former includes toxic effects of Cd on osteoblasts and impediment of calcification at the ossification front by Cd or Fe. The latter indicates nephrogenic osteopenia via hypocalcemia, hypophosphatemia and hyperparathyroidism. Each hypothesis secures solid scientific basis and may not be alternative. Our animal experiments using rats and monkeys demonstrated that hypoestrogenism induced by ovariectomy enhanced Cd toxicity, and osteopenic osteomalacia and tubular nephropathy distinctive to IID could be reproduced by Cd treatment without involvement of malnutrition such as hypovitaminosis D. Vitamin D has been prescribed to IID patients for bone lesions. However, the efficacy of the treatment is unpredictable depending on patients. Our experiments suggest concurrent administration of estradiol helps the vitamin D therapy for IID patients and the removal of Fe at the mineralization front of bone is important for the recovery to normal bone remodeling. <br>

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