Cadmium-Induced Effects on Bone in a Population-Based Study of Women

Abstract

High cadmium exposure is known to cause bone damage, but the association between low-level cadmium exposure and osteoporosis remains to be clarified. Using a population-based women’s health survey in southern Sweden [Women’s Health in the Lund Area (WHILA)] with no known historical cadmium contamination, we investigated cadmium-related effects on bone in 820 women (53–64 years of age). We measured cadmium in blood and urine and lead in blood, an array of markers of bone metabolism, and forearm bone mineral density (BMD). Associations were evaluated in multiple linear regression analysis including information on the possible confounders or effect modifiers: weight, menopausal status, use of hormone replacement therapy, age at menarche, alcohol consumption, smoking history, and physical activity. Median urinary cadmium was 0.52 μg/L adjusted to density (0.67 μg/g creatinine). After multivariate adjustment, BMD, parathyroid hormone, and urinary deoxypyridinoline (U-DPD) were adversely associated with concentrations of urinary cadmium (p < 0.05) in all subjects. These associations persisted in the group of never-smokers, which had the lowest cadmium exposure (mainly dietary). For U-DPD, there was a significant interaction between cadmium and menopause (p = 0.022). Our results suggest negative effects of low-level cadmium exposure on bone, possibly exerted via increased bone resorption, which seemed to be intensified after menopause. Based on the prevalence of osteoporosis and the low level of exposure, the observed effects, although slight, should be considered as early signals of potentially more adverse health effects.

Long-term cadmium exposure and the association with bone mineral density and fractures in a population-based study among women

“…(3)(4)(5)(6) It should be noted, however, that our results indicate an increased risk of osteoporosis at considerably lower Cd exposures. In addition, the results for BMD at the lumbar spine may indicate a greater public health concern than recognized previously.…”

“…Human data support Cdinduced increased bone resorption rather than an effect on bone formation. (6,29,30) Our results on fracture risk suggest, however, that Cd's effect is only partly mediated via lowered BMD. It can be speculated that Cd exposure also results in specific effects on cortical and trabecular bone or in alterations of biomechanical properties that are not detected by DXA; this is also supported by experimental studies.…”

“…(33) Furthermore, the positive association between U-Cd and urinary calcium observed previously (26,29,30) and in this study has been considered a result of Cd-induced tubular damage causing hypercalciuria but may well be a result of Cd-induced increased bone resorption. (29,30) U-Cd also has been shown to be associated with both increased bone resorption and decreased parathyroid hormone concentrations, (6,26) suggesting that the effect on bone was not mediated primarily by Cd-induced tubular damage.…”

“…This severe disease was characterized by renal and bone damage, with bone deformities and multiple fractures occurring as a consequence. (2) Recently, Cd has been associated with low bone mass of the forearm (3)(4)(5)(6) and the hip (7) at considerably lower exposure levels in some but far from all studies. (8)(9)(10)(11) Therefore, a possible role of Cd in the public health context of osteoporosis needs to be evaluated.…”

Cadmium exposure in the population: from health risks to strategies of prevention

“…Clinical features associated with osteoporosis include increased morbidity (pain, physical impairment, decreased quality of life), increased risk of new fractures and increased mortality (Van der Klift et al 2002). Studies among populations from Belgium (Staessen et al 1999;Schutte et al 2008b), Sweden (Järup et al 1998a;Alfvén et al 2000;Å kesson et al 2006), Japan and China Jin et al 2004;Wang et al 2003) showed associations between osteoporosis and low-level environmental Cd exposure. The generally accepted interpretation has been that Cd-induced renal tubular damage (Staessen et al 1994) decreases the calcium reabsorption in the nephron, resulting in hypercalciuria and decreased bone mineral density, and hence increased fracture risk (Järup et al 1998c;Staessen et al 1994) particularly in postmenopausal women (Schutte et al 2008b;Staessen et al 1999) or men in the older age group .…”