Association of environmental cadmium exposure and bone remodeling in women over 50 years of age

Lv, Yingjian; Song, Jia; Xiong, Lili; Huang, Rui; Zhu, Ping; Wang, Ping; Liang, Xiaoyan; Tan, Jianbin; Wang, Jing; Wu, Shuqi; Wei, Qiujing; Yang, Xingfen

doi:10.1016/j.ecoenv.2021.111897

Cited by 14 publications

(9 citation statements)

References 25 publications

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“…showing an association between Cd levels and bone mineral density or osteoporosis, but there is heterogeneity in the results [30][31][32]. Interestingly, a study from China showed that among all women The OR for those with Cd intake >10.63 g was 2.34 (95% CI: 1.23~4.38).…”

Section: Discussionmentioning

confidence: 99%

Blood Cadmium and Lead Levels and Bone Mineral Density Are Negatively Correlated in Adult Women in U.S

et al. 2023

Preprint

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The aim of this study was to investigate the association between blood cadmium levels (BCL) and blood lead levels (BLL) and bone mineral density (BMD) in people aged 20 to 59 years. Using data from the 2011–2018 National Health and Nutrition Examination Survey (NHANES), the researchers used multiple logistic regression models to examine the associations between BCL, BLL, and lumbar BMD. Fitting smooth curves and generalized summation models were also used. In subgroup analyses stratified by sex, the negative correlation between BCL, BLL, and lumbar BMD remained negative in women but not significant in men. In a subgroup analysis stratified by race, an inverse association between blood cadmium and lumbar BMD was observed only in whites. The negative association between BLL and lumbar BMD remained negative among whites, blacks, and Mexican Americans, and showed a U-shaped curve among other races.

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Section: Discussionmentioning

confidence: 99%

Blood Cadmium and Lead Levels and Bone Mineral Density Are Negatively Correlated in Adult Women in U.S

et al. 2023

Preprint

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“…The role of cadmium exposure on bone health has not been well recognized in longitudinal studies. Based on China Cd study that was performed in 1998 ( 24 ), a follow-up survey was conducted in 2006 ( 10 ). We identified the associated factors for follow-up BMD/osteoporosis.…”

Section: Discussionmentioning

confidence: 99%

“…Urinary Cadmium is a biomarker of past and lifetime cadmium exposure ( 2 ). Many cross-sectional studies have shown the association between UCd levels and bone mineral density or risk of osteoporosis ( 10 , 27 , 28 ). Several researchers did not observe statistical differences among the quartiles of UCd concentrations and BMD or osteoporosis ( 9 , 10 , 29 ).…”

Section: Discussionmentioning

confidence: 99%

“…Many cross-sectional studies have shown the association between UCd levels and bone mineral density or risk of osteoporosis ( 10 , 27 , 28 ). Several researchers did not observe statistical differences among the quartiles of UCd concentrations and BMD or osteoporosis ( 9 , 10 , 29 ). Our previous study showed that UCd was associated with BMD changes ( 20 ) during the follow-up.…”

Section: Discussionmentioning

confidence: 99%

“…More importantly, a recent study indicated that that cadmium exposure may play a greater role in bone loss than previously thought ( 1 ). However, negative associations between cadmium levels and bone loss were also reported ( 9 , 10 ). The long-term effects of cadmium on bone had substantial uncertainty ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

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The Association Between Cadmium Exposure and Osteoporosis: A Longitudinal Study and Predictive Model in a Chinese Female Population

Wang

Liu

et al. 2021

Front. Public Health

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Objective: The association between cadmium exposure and osteoporosis has been rarely reported in longitudinal studies. In this study, we investigated the association between osteoporosis and cadmium exposure and developed predictive models in women in a longitudinal cohort.Materials and Methods: In total, 488 women living in southeastern China were included at baseline (1998). Cadmium in blood (BCd) and urine (UCd) and also renal dysfunction biomarkers and bone mineral density (BMD) were determined both at baseline and follow-up. A total of 307 subjects were finally included after excluding subjects that did not have exposure or effect biomarkers. Osteoporosis was defined based on T score ≤ −2.5. Multiple linear regression and multivariate logistic analysis were used to show the association between baseline data and follow-up osteoporosis. Based on the identified associated factors, nomograms were developed to graphically calculate the individual risk of osteoporosis.Results: The baseline BMD in subjects with osteoporosis was significantly lower than that in subjects without osteoporosis (0.59 vs. 0.71 g/cm2, p < 0.05). The prevalence of low bone mass at baseline was higher in subjects with osteoporosis than in those without osteoporosis (23.5 vs. 7.2%, p = 0.001). Logistic regression analysis demonstrated that age [odds ratio (OR) = 1.21, 95% confidence interval (CI): 1.16–1.27], UCd (OR = 1.03, 95% CI: 1.002–1.06) and the presence of low BMD (OR = 3.84, 95% CI: 1.49–9.89) were independent risk factors for osteoporosis. For those subjects with normal baseline BMD, age, UCd, and baseline BMD were also independent risk factors for osteoporosis. The OR value was 1.16 (95% CI: 1.10–1.22) for age, 2.27 (95% CI: 1.03–4.99) for UCd > 10 μg/g creatinine, and 0.39 (95% CI: 0.21–0.72) for BMDbaseline. We developed two nomograms to predict the risk of osteoporosis. The area under the curve was 0.88 (95% CI: 0.84–0.92) for total population and was 0.88 (95% CI: 0.84–0.92) for subjects with normal baseline BMD, respectively.Conclusion: Baseline age, UCd, and BMD were associated with follow-up osteoporosis in women. Nomograms showed good performance in predicting the risk of osteoporosis.

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Cadmium accelerates autophagy of osteocytes by inhibiting the PI3K/AKT/mTOR signaling pathway

Song

et al. 2023

Environmental Toxicology

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Cadmium (Cd) can damage bone cells and cause osteoporosis. Osteocytes are the most numerous bone cells and also important target cells for Cd-induced osteotoxic damage. Autophagy plays important role in the progression of osteoporosis. However, osteocyte autophagy in Cd-induced bone injury is not well characterized. Thus, we established a Cd-induced bone injury model in BALB/c mice and a cellular damage model in MLO-Y4 cells. Aqueous Cd exposure for 16 months showed an increase in plasma alkaline phosphatase (ALP) activity and increase in urine calcium (Ca) and phosphorus (P) concentrations in vivo. Moreover, expression level of autophagyrelated microtubule-associated protein 1A/1B-light chain 3 II (LC3II) and autophagyrelated 5 (ATG5) proteins were induced, and the expression of sequestosome-1 (p62) was reduced, along with Cd-induced trabecular bone damage. In addition, Cd inhibited the phosphorylation of mammalian target of rapamycin (mTOR), protein kinase B (AKT), and phosphatidylinositol 3-kinase (PI3K). In vitro, 80 μM Cd concentrations exposure upregulated LC3II protein expression, and downregulated of p62 protein expression. Similarly, we found that treatment with 80 μM Cd resulted in a reduction in the phosphorylation levels of mTOR, AKT, and PI3K. Further experiments revealed that addition of rapamycin, an autophagy inducer, enhanced autophagy and alleviated the Cd-induced damage to MLO-Y4 cells. The findings of our study reveal for the first time that Cd causes damage to both bone and osteocytes, as well as induces autophagy in osteocytes and inhibits PI3K/AKT/mTOR signaling, which could be a protective mechanism against Cd-induced bone injury.

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Association of environmental cadmium exposure and bone remodeling in women over 50 years of age

Cited by 14 publications

References 25 publications

Blood Cadmium and Lead Levels and Bone Mineral Density Are Negatively Correlated in Adult Women in U.S

Blood Cadmium and Lead Levels and Bone Mineral Density Are Negatively Correlated in Adult Women in U.S

The Association Between Cadmium Exposure and Osteoporosis: A Longitudinal Study and Predictive Model in a Chinese Female Population

Cadmium accelerates autophagy of osteocytes by inhibiting the PI3K/AKT/mTOR signaling pathway

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