Bone Resorption and Environmental Exposure to Cadmium in Women: A Population Study

BACKGROUND Environmental exposure to cadmium decreases bone density indirectly through hypercalciuria resulting from renal tubular dysfunction. OBJECTIVE We sought evidence for a direct osteotoxic effect of cadmium in women. METHODS We randomly recruited 294 women (mean age, 49.2 years) from a Flemish population with environmental cadmium exposure. We measured 24-hr urinary cadmium and blood cadmium as indexes of lifetime and recent exposure, respectively. We assessed the multivariate-adjusted association of exposure with specific markers of bone resorption, urinary hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), as well as with calcium excretion, various calciotropic hormones, and forearm bone density. RESULTS In all women, the effect sizes associated with a doubling of lifetime exposure were 8.4% (p=0.009) for HP, 6.9% (p=0.10) for LP, 0.77 mmol/day (p=0.003) for urinary calcium, -0.009 g/cm(2) (p=0.055) for proximal forearm bone density, and -16.8% (p=0.065) for serum parathyroid hormone. In 144 postmenopausal women, the corresponding effect sizes were -0.01223 g/cm(2) (p=0.008) for distal forearm bone density, 4.7% (p=0.064) for serum calcitonin, and 10.2% for bone-specific alkaline phosphatase. In all women, the effect sizes associated with a doubling of recent exposure were 7.2% (p=0.001) for urinary HP, 7.2% (p=0.021) for urinary LP, -9.0% (p=0.097) for serum parathyroid hormone, and 5.5% (p=0.008) for serum calcitonin. Only one woman had renal tubular dysfunction (urinary retinol-binding protein >338 microg/day). CONCLUSIONS In the absence of renal tubular dysfunction, environmental exposure to cadmium increases bone resorption in women, suggesting a direct osteotoxic effect with increased calciuria and reactive changes in calciotropic hormones.