Measurement of vitamin D3 metabolites in smelter workers exposed to lead and cadmium

Objectives-To investigate the effects of lead and cadmium on the metabolic pathway of vitamin D-3. Methods-Blood and urinary cadmium and urinary total proteins were measured in 59 smelter workers occupationally exposed to lead and cadmium. In 19 of these workers, the plasma vitamin D-3 metabolites, (25-hydroxycholecalciferol (25 OHD3), 24R, 25-dihydroxycholecalciferol (24R,25(OH)(2)D-3) and l alpha, 25-dihydroxycholecalciferol (1 alpha,25(OH)(2)D-3)) were measured together with blood lead. Vitamin D-3 metabolites were measured by radioimmunoassay, (RIA), lead and cadmium by atomic absorption spectrophotometry, and total proteins with a test kit. Results-Ranges for plasma 25(OH)D-3, 24R,25(OH)(2)D-3 and 1 alpha,25(OH)(2)D-3 were 1.0-51.9 ng/ml, 0.6-5.8 ng/ml, and 0.1-75.7 pg/ml, respectively. Ranges for blood lead were 1-3.7 I.mu mol/l, (21-76 mu g/dl), blood cadmium 6-145 nmol/l, and urinary cadmium 3-161 nmol/l. Total proteins in random urine samples were 2.1-32.6 mg/dl. Concentrations of lead and cadmium in blood showed no correlation (correlation coefficient -0.265) but there was a highly significant correlation between blood and urinary cadmium. Concentrations for 24R,25(OH)(2)D-3 were depressed below the normal range as blood and urinary cadmium increased, irrespective of lead concentrations. High cadmium concentrations were associated with decreased plasma l alpha,25(OH)(2)D-3 when lead concentrations were <1.9 mu mol/l and with above normal plasma 1 alpha,25(OH)(2)D-3 when lead concentrations were >1.9 mu mol/l, Kruskal-Wallis analysis of variance (K-W ANOVA) chi(2)=10.3, p=0.006. Plasma 25(OH)D, was negatively correlated with both urinary total proteins and urinary cadmium, but showed no correlation with plasma 24R,25(OH)(2)D-3, l alpha,25(OH)(2)D-3, blood lead, or blood cadmium. Conclusion-Continuous long term exposure to cadmium may result in a state of equilibrium between blood and urinary cadmium. Cadmium concentrations in blood could be predicted from the cadmium concentration of the urine, (regression coefficient +0.35 SE 0.077). Exposure to cadmium alone decreased the concentrations of 1 alpha,25(OH),D, and 24R,25(OH)(2)D-3, whereas exposure to both cadmium and lead increased the concentrations of 1 alpha,25(OH)(2)D-3. It has been suggested that cadmium and lead interact with renal mitochondrial hydroxylases of the vitamin D, endocrine complex. Perturbation of the vitamin D metabolic pathway by cadmium may result in health effects, such as osteoporosis or osteomalacia, risks which are possibly increased in the presence of lead.