Cadmium accelerates bone loss in ovariectomized mice and fetal rat limb bones in culture.

Abstract

Loss of bone mineral after ovariectomy was studied in mice exposed to dietary cadmium at 0.25, 5, or 50 ppm. Results show that dietary cadmium at 50 ppm increased bone mineral loss to a significantly greater extent in ovariectomized mice than in sham-operated controls. These results were obtained from two studies, one in which skeletal calcium content was determined 6 months after ovariectomy and a second in which 45Ca release from 'Ca-prelabeled bones was measured immediately after the start of dietary cadmium exposure. Furthermore, experiments with 4sCa-prelabeled fetal rat limb bones in culture demonstrated that Cd at 10 nM in the medium, a concentration estimated to be in the plasma of mice exposed to 50 ppm dietary Cd, strikingly increased bone resorption, from 27 ± 2% (mean ± SEM) "Ca release in cultures with no added cadmium to 68 ± 6% release in cultures containing cadmium (n -4). These in vitro results indicate that cadmium may enhance bone mineral loss by a direct action on bone. Results of the in vivo studies are consistent with a significant role of cadmium in the etiology of Itai-Itai disease among postmenopausal women in Japan and may in part explain the increased risk of postmenopausal osteoporosis among women who smoke.Osteoporosis affects [15][16][17][18][19][20] million people in the United States and is a major cause ofbone fractures in older persons, particularly postmenopausal women (1). One striking form of postmenopausal bone disease has occurred among women in Toyama prefecture, Japan, in the form of Itai-Itai (OuchOuch) disease, which is characterized by severe osteoporosis/osteomalacia and renal tubular dysfunction (2-5). Elevated levels of cadmium were present in both the diet and drinking water of women with Itai-Itai disease. The Japanese Ministry of Health in May 1968 declared cadmium to be one of the causative factors in the etiology of this bone disease on the basis of epidemiologic data relating disease incidence to cadmium exposure and the finding of high cadmium levels in tissues taken at autopsy from women with the disease (4, 6).The studies reported here were designed on the basis of the unusual finding that 95% of the cases of Itai-Itai disease occurred in postmenopausal women, not in younger women, men, or children (4). Although many studies of cadmiuminduced bone loss had been conducted in male animals or in females with intact ovaries, none had addressed the question of whether the combination of cadmium exposure and ovariectomy (to simulate conditions of postmenopausal hormone depletion) might accelerate the loss of bone calcium that normally occurs after removal of the ovaries. Such results might explain why Itai-Itai disease did not appear until after menopause.Results of our studies show that loss of bone mineral after ovariectomy in female mice was strikingly increased by dietary cadmium exposure. In addition, when cadmium was added at low concentrations (10 nM) to bone cultures, bone resorption was stimulated to an extent similar to that observed after treat...

Mechanisms of Cadmium Mobility and Accumulation in Indian Mustard

“…There is evidence that low-leve1 exposure to Cd, derived from the diet, is associated with renal dysfunction (Buchet et al, 1990). Cd exposure has also been linked with pulmonary emphysema (Ryan et al, 1982) and possibly bone demineralization (Bhattacharyya et al, 1988). Pollution of the biosphere with this toxic metal has accelerated dramatically since the beginning of the industrial revolution (Nriago, 19791, and Cd accumulation in soil and water now poses a major environmental and human health problem, which is in need of an effective and affordable solution.…”

Histopathological analysis for osteomalacia and tubulopathy in itai-itai disease

“…In other words, osteomalacia is caused by the urinary leak of essential metabolites like phosphate and calcium, which is related to tubulopathy that causes defects in renal tubular reabsorption. On the other hand, the direct pathway supposes that Cd directly impairs bone metabolism and osteocytes and alters osteoblast gene expression (Bhattacharyya et al, 1988;Brama et al, 2012;Arbon et al, 2012). Although our results do not rule out the direct pathway, it is believed to be evidence supporting and reconfirming the theory that renal osteomalacia occurs in IID patients.…”

Association between blood cadmium level and bone mineral density reduction modified by renal function in young and middle-aged men

“…Cd has a very long half-life of 10-30 years and hence is accumulated in the body, damages renal tubes [10,31], obstructs calcium absorption in the digestive tract [32] and negatively affects the metabolism of bones [33][34][35]. UCd or BCd are indices of accumulation of cadmium in the renal tubes [36], and BCd correlated closely with UCd [24,37].…”