| Objective:Osteoporosis(OP)has become a major public health problem with the acceleration of the aging society.Metal exposure may have an impact on bone mineral density(BMD),but previous studies focused on the effects of single essential or non-essential metal on BMD.Few studies address the possible associations between metal mixtures and BMD.In addition,there are sex differences of OP risk.However,studies to explore the sex-specific associations of metal exposure with BMD and OP risk are still limited.This study is aimed to explore the sex-specific associations between single metal and metal mixtures with BMD and OP risk,and identified the dominant metals,and explored the combined effect of metal mixtures in the elderly population of 60 years and older.Methods:According to the inclusion and exclusion criteria,we finally included 3854 participants,including 2297 women and 1557 men.Blood cell levels of 22 metals were measured by an inductively coupled plasma mass spectrometer(ICP-MS)and T-scores were determined by quantitative ultrasound,and the values of Tscore were used to represent levels of BMD in our study.We analyzed the sexspecific associations between metal exposure and T-score in all participants,women and men,respectively.Because the number of men with OP was relatively low,we only explored the association between metal exposure and OP risk in women.Firstly,generalized linear regression was used to construct the singlemetal model,and restricted cubic spline regression was used to evaluate the relationships between statistically significant metals from single-metal model with BMD and OP risk.Then,LASSO regression was used to screen the metals that were important for BMD and OP risk,and the selected metals were included in the generalized linear regression to construct multiple-metal model.Finally,we used BKMR models to explore the overall effects of metal mixtures.Results:(1)The associations between single metal exposure with BMD and OP risk:In all participants,there were linear negative correlations between Ba and Mn with BMD levels,and linear positive correlations between Co and Rb with BMD levels.Pb and V were non-linearly correlated with BMD levels.In women,there were linear positive correlation between Rb with BMD levels,and linear negative correlation between Rb with OP risk.Pb and V were non-linearly correlated with BMD and OP risk.In men,there were linear negative correlations between Mn and Ti with BMD levels,while Rb was non-linearly correlated with BMD.(2)The associations between metal mixtures with BMD and OP risk:In all participants,the metal mixture Ba-Pb-Rb-Ti-V was positively correlated with BMD levels.In women,the metal mixture Pb-Rb-V was positively correlated with BMD levels and inversely associated with OP risk.In men,there was no statistically significant association between the metal mixture Cd-Cu-Mn-Rb-Sr-Ti-V with BMD levels.Conclusion:(1)Through series analyses of single-metal methods,we found that Ba,Co,Mn,Pb,Rb and V were related to BMD levels in all participants.And Pb,Rb and V were related to BMD levels in women.And Mn,Ti and Rb were related to BMD levels in men.There were sex-specific associations between the single metal and BMD levels.(2)Through series analyses of multiple-metal methods,we found that there were differences in the metal mixtures of all participants,women and men,and the combined exposure effects existed between metals.In all participants,the metal mixture Ba-Pb-Rb-Ti-V was positively correlated with BMD levels.In women,the metal mixture Pb-Rb-V was positively correlated with BMD levels and inversely associated with OP risk.In men,there was no statistically significant association between the metal mixture Cd-Cu-Mn-Rb-Sr-Ti-V with BMD levels. |