The relationship between Cd toxicity and osteoma- lacia or rickets was first described in Japan in the1950s, when people living in the Jinzu river basin area began developing multiple bone fractures, severe bone pain, and malformations of their long bones (typical features of rickets); a syndrome that became known as Itai-Itai disease (1955) (Nogawa et al. 1975a). Cd intoxication was eventually found to be due to industrial waste discharged into the river from an upstream zinc mine (Inaba et al. 2005). Although the bone complications seen with chronic Cd poisoning were thought to be largely secondary to Cd-induced renal toxicity, and a consequence of renal Fanconi syndrome (see above), hypercalciuria and impaired vitamin D metabolism, more recent studies have found evidence for a direct effect of Cd on bone, resulting from its deposition and storage
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