Cadmium, osteoporosis and calcium metabolism

Abstract

Occupational exposure to cadmium has for long been associated with renal tubular cell dysfunction, osteomalacia with osteoporosis, hypercalciuria and renal stone formation. High environmental exposure in Japan resulting from a stable diet of cadmium contaminated rice caused itai-itai disease, fractures occurring mainly in elderly multiparous women, with a form of osteomalacia, osteoporosis and renal dysfunction. More recently a population based study in Europe, in the vicinity of zinc smelters has shown that low to moderate exposure to cadmium, with a mean urinary excretion of cadmium of the order of 1 microg/g creatinine has been associated with a decrease in bone density, an increased risk of bone fractures in women and of height loss in men. In a population-based study of residents near a cadmium smelter in China, forearm bone density was shown to decrease linearly with age and urinary cadmium in both sexes, suggesting a dose effect relationship between cadmium dose and bone mineral density. A marked increase in the prevalence of fractures was shown in the cadmium-polluted area in both sexes. Concentrations of cadmium in blood and urine were taken as exposure biomarkers, and beta2-microglobulin, retinol binding protein and albumin as biomarkers of effect. A marked dose response relationship between these indicators of exposure and effect was shown. Hypercalciuria, which may progress to osteoporosis, has been taken as a sensitive renal-tubular biomarker of a low level of cadmium exposure. Cadmium may also act directly on bone. Animal studies have shown cadmium to stimulate the formation and activity of osteoclasts, breaking down the collagen matrix in bone. Osteoporosis is the main cause of fracures in post-menopausal women, a common occurrence worldwide, giving rise to disability and a high cost to health services. The identification of cadmium, an environmental pollutant, as one causal factor is highly significant in helping to control the incidence of this complex condition.

The Effects of a Vitamin D–deficient Diet on Chronic Cadmium Exposure in Rats

“…The mechanisms of Cd-induced osteoporosis with osteomalacia, which is the main pathological finding of IID, are not fully understood. The inactive form of vitamin D is activated at the proximal tubules of the kidneys, and dysfunction of the tubules occurs in the early phase of chronic Cd toxicosis (Kazantzis 2004;Kjellström 1992) and IID (Shigematsu, 1984;Takebayashi et al 2000). Thus, the disorder of vitamin D hydroxylation in the kidneys is regarded as one of the important mechanisms of bone pathology in IID patients (Aoshima and Kasuya 1991;Kido 1995;Tsuritani et al 1992).…”

Element Content of Surface and Underground Water Sources around a Cement Factory Site in Calabar, Nigeria

“…Evidence of bioaccumulation was shown by report of higher serum levels of Cd in occupationally exposed individuals; cement factory workers and residents near cement factory compared to unexposed controls [10]. Occupational exposures to Cd have been associated with renal tubular dysfunction with hypercalciuria, renal stone formation, osteomalacia, and osteoporosis [2,18]. Cadmium has also been implicated in respiratory and immune dysfunctions [19,20].…”

Harmful Interactions of Non-Essential Heavy Metals with Cells of the Innate Immune System

“…Cadmium toxicity may also result in osteoporosis by inducing renal tubular dysfunction with consequent increased urinary losses of calcium and phosphate as well as a direct effect on bone osteoblast and osteoclast activity [13][14]. Heavy metal toxicity in the setting of iron-deficiency anaemia may significantly increase the risk of infection as both iron-deficiency [15] and Cd-toxicity impair host responses to infection.…”

“…Other mechanisms of Cd -mediated pro-oxidative activity include: i) inhibition of superoxide dismutase [27]; ii) bonding to sulfhydryl groups, depleting glutathione and protein sulfhydryls, thereby compromising intracellular anti-oxidative defences [28]; iii) activation of 5-lipoxygenase activity, leading to production of the neutrophil/ monocyte chemoattractant, leukotriene B 4 (LTB 4 ), which also sensitizes these cells for increased activity of NADPH oxidase [29]; and iv) oxidative activation of redox-sensitive transcription factors such as nuclear factor kappa B (NFκB) and activator protein 1 (AP-1), which, in turn, activate the expression of genes encoding pro-inflammatory proteins, including iNOS [14,[30][31][32].…”