Exposure to cadmium has been associated with osteoporosis and fracture risk in women and the elderly, but studies in middle-aged men are lacking. In 83 male (ex)workers (mean age 45 years; range 24 to 64 years) in a radiator factory using cadmium-containing solder, we investigated the association between urinary cadmium excretion (as an index of lifetime body burden); bone mineral density (BMD) in the distal forearm, hip, and lumbar spine (by dual-energy X-ray absorptiometry); and urinary calcium excretion. Geometric mean urinary cadmium concentration was 1.02 mg/g of creatinine (5th to 95th percentile 0.17 to 5.51 mg/g). BMD was negatively correlated with urinary exposure to cadmium. The partial correlation coefficients (r) adjusted for age, body-mass index, and current smoking were À0.30 ( p ¼ .008) for BMD in the forearm, À0.27 ( p ¼ .017) in the hip, and À0.17 ( p ¼ .15) in the spine. Urinary calcium correlated positively (r ¼ 0.23, p ¼ .044) with the urinary cadmium excretion. Adjusted for the same covariates, the risk of osteoporosis (defined as a T-score below À2.5 in at least one measured bone site) increased dose dependently. Compared with the lowest tertile of urinary cadmium, the risks were 4.8-and 9.9-fold higher in the middle and highest tertiles, respectively. Only four (5%) men had evidence of renal tubular dysfunction (b 2 -microglobulin > 300 mg/g of creatinine). Even in the absence of renal tubular dysfunction, occupational exposure to cadmium is associated in men with lower BMD values, a higher risk of having osteoporosis, and a higher urinary calcium excretion, suggesting a direct osteotoxic effect of cadmium. ß
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