Abstract
BACKGROUND: Heavy metal exposure is an important cause of reduced bone mineral density (BMD). Epidemiological studies focusing on the effects of mixed heavy metal exposure on BMD in middle-aged and older people are scarce. In single-metal studies, men and women have shown distinct responses of BMD to environmental metal exposure. This study therefore aimed to elucidate the association between mixed heavy metal exposure and BMD and to investigate whether it is sex-specific. METHODS: Data from the 2017-2020 National Health and Nutrition Examination Survey were selected for this cross-sectional study. The study used three statistical methods, i.e., linear regression, Bayesian kernel machine regression (BKMR) modeling, and weighted quartiles (WQS) regression, to explore the association between the urinary concentrations of 11 metals (barium, cadmium, cobalt, cesium, manganese, molybdenum, lead, antimony, tin, thallium, and Tungsten), either individually or as a mixture, and total femoral BMD. RESULTS: A total of 1,031 participants were included in this study. Femoral BMD was found to be higher in men than women. A significant negative correlation between the urinary concentrations of the 10 metals and femoral BMD was found in the overall cohort. Further gender sub-stratified analyses showed that in men, urinary metal concentrations were negatively correlated with femoral BMD, with cobalt and barium playing a significant and non-linear role in this effect. In women, although urinary metal concentrations negatively modulated femoral BMD, none of the correlations was statistically significant. Antimony showed sex-specific differences in its effect. CONCLUSION: The urinary concentrations of 10 mixed heavy metals were negatively correlated with femoral BMD in middle-aged and older participants, and this effect showed gender differences. These findings emphasize the differing role of mixed metal exposure in the process of BMD reduction between the sexes but require further validation by prospective studies.