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

Abstract

Objectives - To investigate the effects of lead and cadmium on the metabolic pathway of vitamin D3. 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 D3 metabolites, (25-hydroxycholecalciferol (25 OHD3), 24R, 25- dihydroxycholecalciferol (24R,25(OH)2D3) and 1α, 25- dihydroxycholecalciferol (1α,25(OH)2D3)) were measured together with blood lead. Vitamin D3 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)D3, 24R,25(OH)2D3 and 1α,25(OH)2D3 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 μmol/l, (21-76 μg/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)2D3 were depressed below the normal range as blood and urinary cadmium increased, irrespective of lead concentrations. High cadmium concentrations were associated with decreased plasma 1α,25(OH)2D3 when lead concentrations were <1.9 μmol/l and with above normal plasma 1α,25(OH)2D3 when lead concentrations were >1.9 μmol/1, Kruskal-Wallis analysis of variance (K-W ANOVA) χ2=10.3, p=0.006. Plasma 25(OH)D3 was negatively correlated with both urinary total proteins and urinary cadmium, but showed no correlation with plasma 24R,25(OH)2D3, 1α,25(OH)2D3, 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 1α,25(OH)2D3 and 24R,25(OH)2D3, whereas exposure to both cadmium and lead increased the concentrations of 1α,25(OH)2D3. It has been suggested that cadmium and lead interact with renal mitochondrial hydroxylases of the vitamin D3 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.