Elsevier

Chemosphere

Volume 282, November 2021, 131150
Chemosphere

Associations of multiple metals with bone mineral density: A population-based study in US adults

https://doi.org/10.1016/j.chemosphere.2021.131150Get rights and content

Highlights

  • Associations of multiple metals with BMD were examined in US adults aged ≥20 years.

  • WQS and BKMR models were applied to estimate the joint effects of multiple metals exposure.

  • Significant over-all effects of Cd, Pb, Hg, Mn, Cu, Se, and Zn were found in relation to BMD.

  • Mn, Pb, and Se are the main contributors to the combined effects on BMD.

  • Synergistic interaction exist between Mn and Pb on BMD.

Abstract

Epidemiologic studies focus on combined effects of multiple metals on bone mineral density (BMD) are scarce. Therefore, this study was conducted to examine associations of multiple metals exposure with BMD. Data of adults aged ≥20 years (n = 2545) from the US National Health and Nutrition Examination Survey (NHANES, 2011–2016) were collected and analyzed. Concentrations of metals were measured in blood (cadmium [Cd], lead [Pb], mercury [Hg], and manganese [Mn]) and serum (copper [Cu], selenium [Se], and zinc [Zn]) using inductively coupled plasma mass spectrometry and inductively coupled plasma dynamic reaction cell mass spectrometry, respectively. The weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were performed to determine the joint effects of multiple metals exposure on lumbar and total BMD. The linear regression analyses showed Pb was negatively associated with BMDs. The WQS regression analyses revealed that the WQS index was inversely related to lumbar (β = −0.022, 95% CI: −0.036, −0.008) and total BMD (β = −0.015, 95% CI: −0.024, −0.006), and Se, Mn, and Pb were the main contributors for the combined effects. Additionally, nonlinear dose–response relationships between Pb, Mn, and Se and BMD, as well as a synergistic interaction of Pb and Mn, were found in the BKMR analyses. Our findings suggested co-exposure to Cd, Pb, Hg, Mn, Cu, Se, and Zn (above their 50th percentiles) was associated with reduced BMD, and Pb, Mn, and Se were the main contributors driving the overall effects.

Introduction

Bone mineral density (BMD) is a commonly used parameter for bone health evaluation. It increases markedly during childhood and adolescence, and most people achieve the peak value at approximately 20 years (Xue et al., 2020). Total body and lumbar spine are two preferred sites suitable for BMD measurement from adolescents to old age (Medina-Gomez et al., 2018). Reduced BMD may result in osteoporosis (OP), which usually progresses silently without symptoms until fractures occur and seriously affects individuals’ health and life quality (Cauley, 2013; Kim et al., 2016). Almost half of women and one in five men suffer a fracture resulting from OP in their lifetime (Greenblatt et al., 2017). Numerous factors, including genetic, nutritional, and metabolic factors, have been identified to associate with BMD reductions (Compston et al., 2019; Ströhle and Hahn, 2016; Trajanoska and Rivadeneira, 2019).

Existing evidence also suggests that exposure to metals, such as cadmium (Cd), lead (Pb), mercury (Hg), manganese (Mn), copper (Cu), selenium (Se), and zinc (Zn), may affect bone health (Galvez-Fernandez et al., 2021; Kim et al., 2016; La-Up et al., 2021; Qu et al., 2018; Sadeghi et al., 2014; Tsai et al., 2016; Wu et al., 2021). Several population-based studies showed that elevated blood Pb, Cd, and Hg levels were positively associated with low BMD (Chen et al., 2014; Kim et al., 2016; H. S. Lim et al., 2016). However, significant correlations between the dietary intake of those heavy metals and bone parameters were not observed (Lavado-García et al., 2017). In addition, a study conducted among African Americans found that children with higher Pb exposure showed higher BMD than those with lower Pb exposure (Campbell et al., 2004). For Mn, one study from Iran showed a positive association between dietary Mn intake level and lumbar BMD in postmenopausal women; Li et al. reported that retired workers with long-term Mn exposure had higher OP risk than controls (Karamati et al., 2014; D. Li et al., 2020). Lower copper levels were associated with low BMD, whereas higher exposure concentrations were observed with increased fracture risk (Qu et al., 2018). Though beneficial effects of Se on BMD were widely reported, the adverse effect of higher Se exposures was also observed (Beukhof et al., 2016; Galvez-Fernandez et al., 2021; Wu et al., 2021). Animal studies indicated that zinc deficiency was associated with reduced BMD, while evidence from epidemiological studies is scarce (Ryz et al., 2009).

Most of existing studies focused on the associations of single-metal exposure with BMD. Minimal is known about the overall health effect of joint exposure to multiple metals, which is a limitation because simultaneous exposure to various metals is more common than exposure to single one. Though several epidemiological studies have investigated the associations of multiple-metal exposure and bone health by adjusting all metals in traditional regression models or introducing interaction analysis, they are still inadequate to deal with the potential correlations among different mixture components or nonlinear associations between exposure and health outcomes (Chen et al., 2014; Li et al., 2020). Multipollutant methods are needed to capture the nature health effects of multiple metals exposure on BMD. The weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models are two widely used multipollutant effect assessment methods that have been applied to estimate the health effects of multiple metals exposure on various health outcomes, such as glucose metabolism, obesity, diabetes mellitus, kidney health, and prostate cancer (Ge et al., 2021; Z. Li et al., 2019; J. T. Lim et al., 2019; Sanders et al., 2019; Y. Wang et al., 2019; Zhang et al., 2019).

Therefore, this study was performed to examine the individual and joint effects of seven heavy metals (measured in whole blood or serum), namely, Cd, Pb, Hg, Mn, Cu, Se, and Zn on BMD comprehensively based on data of US adults from the National Health and Nutrition Examination Survey (NHANES) using the WQS regression and BKMR models.

Section snippets

Study population

All data in this study were collected from the NHANES, a national survey, which was conducted to assess the health and nutritional status of adults and children in the US using complex, multistage probability sampling design. The survey data were released to the public in biennial cycles, and data from three cycles (2011–2012, 2013–2014, and 2015–2016) of NHANES were combined in the current study. Participants who had incomplete data of metal concentrations and/or other covariates were

Characteristics of participants

The participants selection process is presented in Figure S1. A total of 2545 participants (n = 764 in 2011–2012; n = 940 in 2013–2014; n = 841 in 2015–2016) with complete data were included in this study. The survey-weighted descriptive statistics are presented in Table 1. The weighted mean age of participants was 39.40 years, and 47.9% (n = 1220) were women. Significant differences were observed in education, smoking status, alcohol consumption, hypertension, osteoarthritis, thyroid problem,

Discussion

In the present study, the joint effect of seven metals (Cd, Pb, Hg, and Mn in whole blood, and Cu, Se, and Zn in serum) exposure on BMD was evaluated using multiple statistical methods. Pb was found significantly and negatively associated with lumbar BMD in either single- or multiple-metal linear regressions and had a marginal effect on total BMD after adjusting for the six other metals and potential confounders. The findings of WQS regression suggested evident associations between co-exposure

Conclusion

In summary, the WQS regression and BKMR models were applied to find the joint effects of multiple metals on lumbar and total BMDs among US adults. Co-exposure to the seven studied metals was associated with reduced BMDs, and Mn, Pb, and Se were the main contributors. Moreover, the synergistic action of Pb and Mn exposures on BMDs were discovered. Given the cross-sectional design of the current study, further prospective and experimental studies are worth conducting to verify our findings and

Author contributions

Mu-hong Wei: Investigation, Methodology, Writing - Original draft preparation, Writing - Review & Editing. Yuan Cui: Investigation, Methodology, Writing - Review & Editing. Hao-long Zhou: Investigation, Writing - Review & Editing. Wen-jing Song: Investigation, Writing - Review & Editing. Dong-sheng Di: Investigation, Writing - Review & Editing. Ru-yi Zhang: Investigation, Writing - Review & Editing. Qin Huang: Investigation, Writing - Review & Editing. Jun-an Liu: Conceptualization, Writing -

Funding

The work was funded by the National Natural Science Foundation of China [Grant no. 72061137006, 81573235], the Natural Science Foundation of Hubei Province [Grant no. 2019CFB647], and the Fundamental Research Funds for the Central Universities [Grant no. 2019kfyXKJC003].

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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