In an attempt to establish a primate model of chronic
cadmium toxicosis, we ovariectomized cynomolgus monkeys and treated them with
CdCl2 by repeated
intravenous injections for 13 to 15 months. The animals showed normocytic-normochromic
anemia. The
cadmium treatment resulted in increases of urinary
enzyme activity indicative of renal tubular degeneration. Histopathology of the kidney revealed renal proximal tubular
atrophy accompanied by interstitial
fibrosis. Decreased bone mineral density was evident in the trabecular and cortical zones of the lumbar vertebra and femur, with osteoid accumulation around the trabeculae and Haversian canals.
Iron deposition at the mineralization front and osteoclasts
hyperplasia were indicative of impairment of bone mineralization and an increase of resorption. Blood inorganic
phosphorus and 1α,25(
OH)2
vitamin D3 levels decreased and urinary
deoxypyridinoline level increased in
cadmium-treated animals. The renal and bone lesions closely resemble those of
itai-itai disease patients, the most severe case of
cadmium toxicosis in terms of clinical chemistry and histopathology. Thus, ovariectomized monkeys chronically exposed to
cadmium can serve as a primate
itai-itai disease model, which is beneficial for developing novel therapeutic methods, investigating the mechanisms of the renal and bone lesions, and establishing more clearly defined criteria for diagnosing the disease.