To explore the association between mixed exposure to low concentrations of heavy metals (cadmium, lead, mercury) and bone density, as well as the mediating effects of alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BAP), parathyroid hormone (PT), calcium (Ca), and phosphorus (P).

A cross-sectional study was conducted based on NHANES survey data, including a total of 1 465 participants. Polynomial logistic regression was used to analyze related risk factors, and Bayesian Kernel Machine Regression (BKMR) was employed to assess the impact of mixed exposure to cadmium, lead, and mercury on bone density. The mediation effects of ALP, BAP, PT, Ca, and P in the relationship between exposure to cadmium (Cd), lead (Pb), mercury (Hg), and bone density were analyzed using the Mediation package in R software (Bootstrap method).

The results of polynomial logistic regression indicated that the risk of bone loss increased at the third quartile (T3) of Cd concentration (OR=1.56, 95%CI: 1.08-2.26); the risk also increased at the second quartile (T2) of Pb concentration (OR=1.49, 95%CI: 1.06-2.08). Conversely, the risk of osteoporosis decreased at T3 of Hg concentration (OR=0.38, 95%CI:0.15-0.94). BKMR model analysis revealed that increased concentrations of cadmium, lead, and mercury were associated with a decrease in bone density scores (T-score), with posterior inclusion probabilities for Cd, Pb, and Hg being 1, 1, and 0.47, respectively. Mediation analysis showed that Cd influenced bone density through the mediating effects of ALP and Ca, with mediation proportions of -32.3% and -64.9%, respectively. Hg affected bone density through the mediating effects of ALP and BAP, with mediation proportions of 7.3% and 61.8%. Pb influenced bone density through the mediating effects of ALP, BAP, and PT, with mediation proportions of 38.9%, 97.6%, and 1.5%, respectively.

There is a negative correlation between low concentrations of mixed exposure of cadmium, lead, and mercury and T-score, and the mediating effects of ALP, BAP, PT, and Ca are statistically significant.