Osteoporosis cadmium effect

Itai-itai disease is considered the most advanced stage of chronic Cd intoxication. Cadmium-induced bone effects are also suggested to occur in the more advanced stage. Originally, attention was focused on osteomalacia in the diagnosis of this disease. Recent studies, however, showed that osteopenia, a main characteristic of osteoporosis, can be detected in the early stage of chronic Cd intoxication. 

A striking and unexpected outcome of the Cadmibel study was the clear-cut interference of fhe low-level Cd exposure with calcium metabolism. For example, when urinary Cd excretion increased twofold, serum alkaline phosphatase activity and urinary calcium excretion rose by 3-4% and 0.25 mmol/24h respectively [142]. The dose (CdU)-response rate of increased calciuria (>9.8 mmol/24h) suggested a 10% prevalence of hy-percalciuria when CdU exceeded 1.9 pg Cd/24h [38]. Hypercalciuria should be considered an early adverse tubulotoxic effect, because it may exacerbate the development of osteoporosis, especially in the elderly. A prospective study from 1992-1995 (median follow-up of 6.6 years) in the above-mentioned Cadmibel subcohort from the rural area showed for a two-fold increase in urinary Cd a significant (p<0.02) decrease of 0.01 g/ cm in forearm bone density in post-menopausal women. In addition, the relative risks associated with doubled urinary Cd were 1.73 (95% Cl 1.16-2.57 p=0.007) for fractures in women and 1.60 (0.94-2.72 p=0.08) for height loss in men. Cadmium excretion in the four... 

Chronic effects of exposure to elevated cadmium concentrations lead to lung emphysema, renal damage and softening of bones. The atomic diameter of cadmium is very similar to that of calcium which leads to the substitution of calcium by cadmium and its building into the bones which results in osteomyelitis and osteoporosis. Experiments carried out on animals showed cancerous effects of cadmium and its influence on zinc metabolism (Lehman and Poisner, 1984). 

Osteomalacia and osteoporosis are reported primarily in patients (95% females) with itai-itai disease, and osteomalacia has been observed in cadmium industry workers, the majority of whom are male (Goyer 1991). While the mechanisms for these effects are not well known, cadmium disruption of calcium metabolism may be important. One of the manifestations of renal injury in cadmium-exposed populations is calcuria and negative calcium balance. It is not clear whether these effects on calcium metabolism occur secondary to renal injury, or whether there is a direct effect on calcium pathways (see discussion of calmodulin-calcium-cadmium interactions in Sect. B.I). 

An increased risk of osteoporosis correlates with the cadmium burden in different populations, especially for post-menopausal women. Cadmium exposure decreases bone mineral density and thus increases the risk for fractures. These effects on the bones are related to kidney malfunction and poor calcium reabsorption in the nephron, as witnessed by (hyper)calciuria. The consequences of cadmium exposure on the human skeleton were particularly obvious for Japanese living along the Jinzu river basin in the 20th century. Water and rice contaminated by cadmium as a result of zinc-mining activities upstream afflicted the local people with the Itai-Itai disease, a particularly acute and painful form of osteomalacia [44]. 

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