The association between environmental cadmium exposure and parathyroid hormone levels

The association between environmental cadmium exposure and parathyroid hormone levels | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report The association between environmental cadmium exposure and parathyroid hormone levels Hongye Tang, Jiangchuan Wang, Rongzhou Wang, Nandong Hu, Zicheng Wei, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2718953/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 May, 2023 Read the published version in Biological Trace Element Research → Version 1 posted 4 You are reading this latest preprint version Abstract Cadmium exposure is associated with renal dysfunction and bone damage. Chronic kidney disease and bone loss are also related to parathyroid hormone (PTH). However, whether cadmium exposure affect PTH level is not completely understood. In this study, we observed the association between environmental cadmium exposure and parathyroid hormone levels in a Chinese population. A ChinaCd study was performed in China in 1990s which included 790 subjects living in heavily, moderately and low cadmium polluted area. 354 of them (121men and 233 women) also had the data of serum PTH. The cadmium levels in blood (BCd) and urine (UCd) were determined by flame atomic absorption spectrometry. Serum PTH was detected by immunoradiometric assay. Renal function was assessed based on urinary N-acetyl-βd-glucosaminidase (UNAG) and urinary albumin (UALB). The median BCd and UCd levels were 4.69 µg/L and 5.50 µg/g creatinine. The BCd, UCd, UNAG and UALB levels in subjects with low PTH (< 5.0 ng/L) were significantly higher than those with PTH ≥ 5.0 ng/L (p < 0.05 or p < 0.01). Spearman correlation analysis also showed that UCd level was negatively correlated to PTH levels (r = -0.17, p = 0.008). A weak correlation was also observed between BCd and PTH level (r = -0.11, p = 0.09). Univariable and mutivariable logistic regression analysis demonstrated that high BCd (> 10 µg/L) (odds ratio (OR) = 2.26, 95% confidence interval (CI):1.10–4.63; OR = 2.36, 95%CI: 1.11–5.05) and UCd level (> 20 µg/g cr) (OR = 2.84, 95%CI:1.32–6.10; OR = 2.97, 95%CI: 1.25–7.05) were associated with high risk of low PTH. Our data showed that environmental cadmium exposure was associated with low PTH level. cadmium renal dysfunction parathyroid hormone Figures Figure 1 Introduction Cadmium is a type of heavy metal that widely distributes in the environment. Cadmium is also widely used in industrial field which may cause environmental pollution through the waste gas, water or residue. Then cadmium can accumulate in mainly cereals or vegetables and enter the human body via the food chain [ 1 ]. Smoking is also an important source of cadmium exposure in general population [ 2 ]. Cadmium in the human body has a half-life of 10–30 years [ 3 , 4 ]. Cadmium exposure have been linked to many adverse effects, including kidney dysfunction, liver damage, cardiovascular diseases and bone damage [ 5 ]. Bone is one of the critical organs for cadmium exposure. Epidemiological study, animal model and in vitro study all showed that cadmium exposure is associated with osteoporosis or bone fracture [ 6 ]. Cadmium exposure may directly affect the activity of osteoblast or osteocalst. In addition, cadmium exposure can cause renal dysfunction [ 7 ], and cadmium-related bone loss maybe secondary to renal damage. However, the exact mechanisms has not been complete understood. Parathyroid gland is an important organ that regulates the calcium and phosphate metabolism by secreting parathyroid hormone (PTH). Secondary hyperparathyroidism is usually occurred in response to declining kidney function or deficiency in bioactivate vitamin D [ 8 ]. Interestingly, cadmium exposure is related to renal tubular damage and reduced synthesis of calcitriol. Dose cadmium exposure affect the secretion of PTH? Few studies have focused on such association. Ibrahim et al. [ 9 ] showed that plasma PTH levels in subjects with occupational cadmium exposure was significantly lower than those in control. However, the sample size of that study is small (n = 94) and that study is based on occupational cadmium exposure. Such association was also reported in several female population [ 1 , 10 , 11 ]. The association between environmental cadmium exposure and PTH level in total population is still unknown. In this study we observed the association between cadmium exposure and PTH level in a Chinese population with environmental cadmium exposure. Methods Study population The subjects living in three cadmium polluted areas were included in this study. The detailed information about participants had been described in our previous studies [ 12 , 13 ]. Briefly, a cadmium smelting plant that put into operation in 1961 located in Jiaoweibao area which caused heavy cadmium pollution to the environment, in particular to water system. The polluted water was used to irrigate the paddy by the residents. The cadmium concentration in rice was significantly higher than the national standard (2.4 mg/kg vs 0.1 mg/kg). Two areas, 12 km (Nanbaixiang) and 40 km (Yantou) away from the smelter, were also selected in this study. The cadmium concentration in rice were 0.48 mg/kg (moderately polluted area) and 0.05 mg/kg (control area), respectively. The participants living in the three areas had similar diet style, lifestyles and socioeconomic status. A total of 790 persons were surveyed. All participants completed a questionnaire to collect the demographic information, information on cadmium exposure, drink and smoking habits, medical history and menopausal status (women). This study was approved by the Institutional Review Board of Fudan university. Inform consent was obtained from each subjects. Declare of Helsinki was followed during the study. Cadmium Determination The detailed information on cadmium measurement had been described in our previous study [ 14 ]. Briefly, 1.0 ml of venous blood was collected in tube containing EDTA anticoagulant which was used for the determination of blood cadmium (BCd). 10 ml morning urine was collected for determination of urinary cadmium (UCd) and renal function biomarkers. UCd and BCd were measure by graphite furnace atomic absorption spectrophotometry. The detection limit was 0.05 µg/L. Renal Function Biomarker And Pth Determination Urinary N-acetyl-βd-glucosaminidase (UNAG) and urinary albumin (UALB) were selected as renal function biomarkers. The determination methods had been reported in our previous studies [ 13 , 14 ]. Briefly, UNAG was determined using a method as described by Tucker et al.(1975). UALB was determined using enzyme-linked immunosorbent assay (ELISA). UCd, UANG and UALB were adjusted with creatinine (cr) and showed as µg/g cr, U/g cr and mg/g cr, respectively. Serum c-terminal parathyroid hormone (PTH) was assessed by immunoradiometric assay (Beckman, USA). 125I-PTH-M and PTH-M in the serum could competitive bind with antibody. The separation reagent was added. Then the radioactivity count of precipitant was measured (XH-6080, radioimmunoassay counter, China). The radioactivity count was negatively related to the serum PTH levels. The coefficient of variation (CV%) for intra and inter assay is lower than 8%. Urinary phosphates, calcium and creatinine were determined by automatic biochemical analyzer. Low PTH was defined if serum PTH < 5 ng/L based on the first quartile of PTH in total population. Serum PTH was determined in 371 subjects (160 in heavy polluted area, 99 in moderate polluted area and 95 in control). Statistical analysis The data management and analysis was performed by SPSS20.0 (SPSS Inc, Chicago, IL, USA). The continuous data were shown as mean ± SD and was compared by Independent-sample T test, or was shown as median (IQR) and was compared by Mann-Whitney U-test. Multivariate logistic regression was adopted to show the association between cadmium levels and PTH. P < 0.05 was statistically significant. Results Characteristics of study population After excluding those subjects with data missing, a total of 354 subjects were included in this study. The characteristics of study subjects is shown in Table 1 . The UCd, BCd, UNAG and UALB levels in subjects with low PTH were significant higher than those with PTH > 5.0 ng/L (p < 0.05 or p < 0.01). No statistical differences were observed in age, urinary calcium and phosphate level between subjects with low PTH and those with PTH ≥ 5.0 ng/L. Table 1 Characteristics of study population Total (n = 354) PTH < 5.0 ng/L (n = 85) PTH ≥ 5.0 ng/L (n = 269) p Age 51.71 ± 15.35 51.3 ± 10.7 50.4 ± 11.0 0.49 Height (cm) 158.1 ± 7.8 158.3 ± 8.9 158.3 ± 7.5 0.97 Weight (kg) 60.3 ± 10.7 59.5 ± 12.1 60.6 ± 10.4 0.35 BCd (µg/L) 4.69 (2.10–9.81) 6.88 (3.01–11.63) 4.22 (1.88–9.04) 0.007 UCd (µg/g cr) 5.50 (2.69–12.26) 7.68 (3.41–14.64) 5.03 (2.55–11.75) 0.024 UNAG (U/g cr) 5.17 (2.16–11.19) 6.65 (3.20-11.56) 4.75 (1.81–10.97) 0.04 UALB (mg/g cr) 4.50 (2.08–10.20) 6.20 (2.50–13.30) 4.30 (1.90–9.30) 0.02 PTH (ng/L) 7.34 (5.08–15.46) 3.71 (2.61–4.41) 8.67 (6.62–20.40) < 0.001 UP (g/L) 0.31 (0.19–0.47) 0.32 (0.22–0.52) 0.33 (0.20–0.48) 0.38 UCa (mmol/dL) 0.35 (0.22–0.53) 0.37 (0.25–0.59) 0.38 (0.22–0.54) 0.65 The Association Between Pth And Cadmium Level UCd level was negatively correlated to PTH levels (r=-0.17, p = 0.008) (Fig. 1 ). A weak correlation was also observed between BCd and PTH level (r= -0.11, p = 0.09). Subsequently, we showed the association between cadmium level and PTH by logistic regression analysis. BCd and UCd levels were associated with risk of low PTH (odds ratio(OR) = 1.04, 95% confidence interval (CI):1.001–1.07; OR = 1.03, 95%CI:1.001–1.05) (Table 2 ). Table 2 The association between UCd /BCd (continuous data) and low level of PTH Model 1 Model 2 BCd (µg/L) 1.03 (1.01–1.06) 1.04 (1.001–1.07) Age (year) 0.99 (0.97–1.02) 0.99 (0.97–1.01) Sex (female vs male) 1.15 (0.70–1.90) 1.26 (0.74–2.14) UANG (U/g cr) 1.003 (0.99–1.02) 0.99 (0.97–1.01) UALB (mg/g cr) 1.01(0.99–1.03) 1.01 (0.99–1.03) UCd (µg/g cr) 1.02(1.001–1.05) 1.03 (1.001–1.05) Age (year) 0.99 (0.97–1.02) 0.99 (0.97–1.02) Sex (female vs male) 1.15 (0.70–1.90) 1.29 (0.76–2.17) UANG (U/g cr) 1.003 (0.99–1.02) 0.99 (0.97–1.02) UALB (mg/g cr) 1.01(0.99–1.03) 1.01 (0.99–1.04) Model 1 Univariable logistic regression analysis Model 2 multivariable logistic regression analysis; model 2 was additionally adjusted with urinary Ca and P levels. Then we divided the BCd and UCd into categorical data. Univariable and mutivariable logistic regression analysis showed that high BCd (> 10 µg/L) (OR = 2.26, 95%CI:1.10–4.63; OR = 2.36, 95%CI: 1.11–5.05) and UCd level (> 20 µg/g cr) (OR = 2.84, 95%CI:1.32–6.10; OR = 2.97, 95%CI: 1.25–7.05) were associated with high risk of low PTH (Table 3 ). Table 3 The association between UCd /BCd (categorical data )and low level of PTH Model1 Model 2 Model3 UCd 20 2.84(1.32–6.10) 2.91 (1.27–8.66) 2.97 (1.25–7.05) BCd 10 2.26(1.10–4.63) 2.31(1.09–4.90) 2.36(1.11–5.05) Model 2 was adjusted with age and renal function Model 3 was additionally adjusted with urinary Ca and P levels. Discussion Cadmium exposure can cause kidney and bone damage. Severe kidney damage is also a reason for secondary hyperparathyroidism which produce high level of PTH. Hyperparathyroidism could induce excessive bone resroption and result in osteoporosis or bone fracture. We speculated that there may be a link between cadmium exposure and PTH. However, few studies have focused on such association [ 9 , 15 ]. Based on ChinaCd study, our data showed that cadmium levels were correlated with serum PTH levels. High BCd or UCd both associated with low PTH levels. The association between cadmium exposure and PTH levels have been reported in several animal or epidemiological studies. However, the results are not consistent. Youness et al. [ 16 ] and Ando et al. [ 17 ] investigated the impact of cadmium on osteoporosis in rats, and they found that the PTH level in cadmium-treated rats was significantly higher than that in control. A population study in Japan also reported that the PTH level was higher in cadmium-exposed subjects than that in non-exposed individuals [ 18 ]. The sample size in that study is relatively small, only 41 cadmium-exposed subjects and 17 controls. Moreover, the exposure levels may be high because subjects with itai-itai disease were included in this study. Several studies in Europe also showed the association between PTH levels and BCd/UCd in populations with environmental exposure [ 1 , 10 , 11 ]. Those studies all showed that UCd or BCd level were negatively associated with PTH level. However, those studies were focused on female population. Our study showed that the risk of low PTH increased with the increasing of BCd or UCd. Then we also found that high level of cadmium exposure was associated with low PTH level in total population. Our those findings were consistent with previous European studies. A recent study based on US National Health and Nutrition Examination Survey also showed that BCd was significantly associated with PTH (OR = 0.97, 95% CI: 0.95–0.99 for continuous data; OR = 0.94, 95% CI: 0.91–0.97 for quartile variable). How cadmium affect PTH is not completely clarified. Cadmium exposure may result in elevation of serum calcium by inducing excessive bone absroption. The increased bone resorption and high serum calcium would cause a compensatory decrease in PTH [ 1 ]. In addition, cadmium may direct affect the ultrastructure of the parathyroid gland [ 19 ]. High levels of cadmium exposure may affect parathyroid gland and inhibit PTH synthesis and secretion. Further studies are needed. There are several limitations in our study. First, the threshold for low PTH was based on the first quartile of PTH in total population, not based on clinical cut-off value. Second, we did not show the possible mechanism of cadmium effects on PTH. Third, our study was cross-sectional design. Longitudinal studies may be better to show such association. Finally, serum calcium and phosphate were not determined in this study. But no significant differences were observed in the urinary calcium and phosphate between subjects with low PTH and PTH ≥ 5.0 ng/L. In conclusion, based on data of ChinaCd study, we showed that BCd and UCd levels were correlated to PTH. Risk of low PTH increased with the increasing of cadmium levels. High level of cadmium exposure caused decrease of serum PTH level. Declarations Conflict of interest The authors declare that there are no conflicts of interest. Ethical approval This study was approved by Ethic Committee of Fudan University. Consent to participate Inform consent was obtained from each subjects. Credit author statement Jiangchuan Wang: Methodology, Formal Analysis, Writing-Original Draft; Hongye Tang: Methodology, Formal Analysis, Writing-Original Draft; Rongzhou Wang: Methodology, Formal Analysis, Writing-Original Draft; Nandong Hu: Formal Analysis, Writing-Original Draft; Zicheng Wei: Formal Analysis, Writing-Original Draft; Guoying Zhu: Methodology, Formal Analysis, Writing-Review & Editing; Xiao Chen: Conceptualization, Methodology, Formal Analysis, Writing-Original Draft, Writing-Review & Editing; Taiyi Jin: Conceptualization, Methodology, Writing-Review & Editing. Acknowledgments This study was funded by National Natural Science foundation of China (No. 81773460) and the European Union (Sixth Framework Programme; PHIME; FOOD-CT-2006-016253). The article reflects only the authors’ views and the European Union is not liable for any use that may be made of the information. References Akesson A, Bjellerup P, Lundh T, Lidfeldt J, Nerbrand C, Samsioe G, Skerfving S, Vahter M (2006) Cadmium-induced effects on bone in a population-based study of women. Environ. Health. Perspect. 114(6): 830–834. Filippini T, Michalke B, Malagoli C, Grill P, Bottecchi I, Malavolti M, Vescovi L, Sieri S, Krogh V, Cherubini A, Maffeis G, Modenesi M, Castiglia P, Vinceti M (2016) Determinants of serum cadmium levels in a Northern Italy community: A cross-sectional study. Environ. Res. 150: 219–226. Lunyera J, Smith SR (2017) Heavy metal nephropathy: considerations for exposure analysis. Kidney. Int. 92: 548–550 Nordberg G (1996) Current issues in low-dose cadmium toxicology: Nephrotoxicity and carcinogenicity. Environmental Science 4: 133–147. World Health Organization. Exposure to cadmium: A major public health concern. 2010. Reyes-Hinojosa D, Lozada-Pérez CA, Zamudio Cuevas Y, López-Reyes A, Martínez-Nava G, Fernández-Torres J, Olivos-Meza A, Landa-Solis C, Gutiérrez-Ruiz MC, Rojas Del Castillo E, Martínez-Flores K (2019) Toxicity of cadmium in musculoskeletal diseases. Environ. Toxicol. Pharmacol. 72:103219. Satarug S (2018) Dietary Cadmium Intake and Its Effects on Kidneys. Toxics. 6(1): 15. Cunningham J, Locatelli F, Rodriguez M (2011) Secondary hyperparathyroidism: pathogenesis, disease progression, and therapeutic options. Clin. J. Am. Soc. Nephrol. 6(4): 913–921. Ibrahim KS, Beshir S, Shahy EM, Shaheen W (2016) Effect of Occupational Cadmium Exposure on Parathyroid Gland. Open. Access. Maced. J. Med. Sci.4(2): 302–306. 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Chen X, Chen X, Wang Y, Wang X, Wang M, Liang Y, Zhu G, Jin T (2020) A nomogram for predicting the renal dysfunction in a Chinese population with reduction in cadmium exposure based on an 8 years follow up study. Ecotoxicol. Environ. Saf. 191:110251 Jin T, Nordberg M, Frech W, Dumont X, Bernard A, Ye TT, Kong Q, Wang Z, Li P, Lundström NG, Li Y, Nordberg GF (2002) Cadmium biomonitoring and renal dysfunction among a population environmentally exposed to cadmium from smelting in China (ChinaCad). Biometals. 15(4):397–410. Sang Z, Zhang H, Ma W, Dong Y, Shi B (2023) Parathyroid hormones in relation to serum cadmium and lead: the NHANES 2003–2006. Environ. Sci. Pollut. Res. Int. 30(7): 18491–18498. Youness ER, Mohammed NA, Morsy FA (2012) Cadmium impact and osteoporosis: mechanism of action. Toxicol. Mech. Methods. 22(7): 560–567. Ando M, Shimizu M, Matsui S, Sayato Y, Takeda M (1987) Influence of cadmium on the metabolism of vitamin D3 in rats. Toxicol. Appl. Pharmacol. 89(2): 158–164. Nogawa K, Tsuritani I, Kido T, Honda R, Yamada Y, Ishizaki M (1987) Mechanism for bone disease found in inhabitants environmentally exposed to cadmium: decreased serum 1 alpha, 25-dihydroxyvitamin D level. Int. Arch. Occup. Environ. Health. 59(1): 21–30. Isono H, Shoumura S, Ishizaki N, Hayashi K, Yamahira T, Yamada S (1979) Effects of cadmium on the ultrastructure of the mouse parathyroid gland. Acta. Anat. (Basel). 105(1): 50–55. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 04 May, 2023 Read the published version in Biological Trace Element Research → Version 1 posted Editorial decision: Major revision 22 Mar, 2023 Editor assigned by journal 22 Mar, 2023 Submission checks completed at journal 21 Mar, 2023 First submitted to journal 21 Mar, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2718953","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":185453372,"identity":"ea487f91-7ac0-4cd5-80b7-d7257ea3e301","order_by":0,"name":"Hongye Tang","email":"","orcid":"","institution":"Affiliated Hospital of Nanjing University of Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hongye","middleName":"","lastName":"Tang","suffix":""},{"id":185453373,"identity":"d29e0fa6-0fa5-4f78-acc1-6a6a35abcce5","order_by":1,"name":"Jiangchuan Wang","email":"","orcid":"","institution":"Affiliated Hospital of Nanjing University of Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jiangchuan","middleName":"","lastName":"Wang","suffix":""},{"id":185453374,"identity":"5c286a8d-70b5-43ed-a5ab-ea561fa58400","order_by":2,"name":"Rongzhou Wang","email":"","orcid":"","institution":"Affiliated Hospital of Nanjing University of Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Rongzhou","middleName":"","lastName":"Wang","suffix":""},{"id":185453375,"identity":"ff5a0323-e6b8-4753-a74c-9cebc189fd4b","order_by":3,"name":"Nandong Hu","email":"","orcid":"","institution":"Affiliated Hospital of Nanjing University of Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Nandong","middleName":"","lastName":"Hu","suffix":""},{"id":185453376,"identity":"e43b32fd-ef39-4085-ae2e-f87b65c7151f","order_by":4,"name":"Zicheng Wei","email":"","orcid":"","institution":"Affiliated Hospital of Nanjing University of Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zicheng","middleName":"","lastName":"Wei","suffix":""},{"id":185453377,"identity":"1fd7d293-adc2-4c02-ac89-7dd7daea8aeb","order_by":5,"name":"Guoying Zhu","email":"","orcid":"","institution":"Fudan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Guoying","middleName":"","lastName":"Zhu","suffix":""},{"id":185453378,"identity":"5bffb13e-2b4c-4fb4-a778-10d188e5e9ae","order_by":6,"name":"Taiyi Jin","email":"","orcid":"","institution":"Fudan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Taiyi","middleName":"","lastName":"Jin","suffix":""},{"id":185453379,"identity":"b6ee6597-1caa-4428-b94f-49fadb57c145","order_by":7,"name":"Xiao Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAp0lEQVRIiWNgGAWjYDACCSBOYLDh4edvIE1LmozkjAOkaGFgOGxj0JBApA7+2T1mEg93nOcxYDjA+OFjDjGW3DmWJpF45jaPOXMDs+TMbURoMZBIPnYjse02j2XDATZmXuK0JLYBtZzjMTiQQLQWsC0HSNAicSMt/UdiWzKP5IyDzcT5hX9GjrHhzzY7e37+5oMfPhKjBQkwNpCmfhSMglEwCkYBbgAA8kM1RW83MIIAAAAASUVORK5CYII=","orcid":"","institution":"Affiliated Hospital of Nanjing University of Chinese Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Xiao","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2023-03-21 14:16:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2718953/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2718953/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s12011-023-03689-x","type":"published","date":"2023-05-04T20:40:48+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":34735901,"identity":"3668053c-b1c2-4297-a9c0-6b3161f8793a","added_by":"auto","created_at":"2023-03-23 19:42:39","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":155391,"visible":true,"origin":"","legend":"\u003cp\u003eThe correlation between Cd exposure level (UCd and BCd) and PTH levels in women. PTH levels were decreased with the increasing of UCd (r = - 0.17, p = 0.008) and BCd (r = -0.11, p = 0.09).\u003c/p\u003e","description":"","filename":"Onlinefigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-2718953/v1/98054079adc36b2e0b825ad8.png"},{"id":44729248,"identity":"b9b19cd3-960d-4c4e-8fad-acfb99406ec5","added_by":"auto","created_at":"2023-10-16 21:14:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":348581,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2718953/v1/35828a42-2b6c-4c8a-b7fd-e85cc7d3dda6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The association between environmental cadmium exposure and parathyroid hormone levels","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCadmium is a type of heavy metal that widely distributes in the environment. Cadmium is also widely used in industrial field which may cause environmental pollution through the waste gas, water or residue. Then cadmium can accumulate in mainly cereals or vegetables and enter the human body via the food chain [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Smoking is also an important source of cadmium exposure in general population [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Cadmium in the human body has a half-life of 10\u0026ndash;30 years [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Cadmium exposure have been linked to many adverse effects, including kidney dysfunction, liver damage, cardiovascular diseases and bone damage [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBone is one of the critical organs for cadmium exposure. Epidemiological study, animal model and in vitro study all showed that cadmium exposure is associated with osteoporosis or bone fracture [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Cadmium exposure may directly affect the activity of osteoblast or osteocalst. In addition, cadmium exposure can cause renal dysfunction [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], and cadmium-related bone loss maybe secondary to renal damage. However, the exact mechanisms has not been complete understood.\u003c/p\u003e \u003cp\u003eParathyroid gland is an important organ that regulates the calcium and phosphate metabolism by secreting parathyroid hormone (PTH). Secondary hyperparathyroidism is usually occurred in response to declining kidney function or deficiency in bioactivate vitamin D [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Interestingly, cadmium exposure is related to renal tubular damage and reduced synthesis of calcitriol. Dose cadmium exposure affect the secretion of PTH? Few studies have focused on such association. Ibrahim et al. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] showed that plasma PTH levels in subjects with occupational cadmium exposure was significantly lower than those in control. However, the sample size of that study is small (n\u0026thinsp;=\u0026thinsp;94) and that study is based on occupational cadmium exposure. Such association was also reported in several female population [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The association between environmental cadmium exposure and PTH level in total population is still unknown. In this study we observed the association between cadmium exposure and PTH level in a Chinese population with environmental cadmium exposure.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eThe subjects living in three cadmium polluted areas were included in this study. The detailed information about participants had been described in our previous studies [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Briefly, a cadmium smelting plant that put into operation in 1961 located in Jiaoweibao area which caused heavy cadmium pollution to the environment, in particular to water system. The polluted water was used to irrigate the paddy by the residents. The cadmium concentration in rice was significantly higher than the national standard (2.4 mg/kg vs 0.1 mg/kg). Two areas, 12 km (Nanbaixiang) and 40 km (Yantou) away from the smelter, were also selected in this study. The cadmium concentration in rice were 0.48 mg/kg (moderately polluted area) and 0.05 mg/kg (control area), respectively. The participants living in the three areas had similar diet style, lifestyles and socioeconomic status. A total of 790 persons were surveyed. All participants completed a questionnaire to collect the demographic information, information on cadmium exposure, drink and smoking habits, medical history and menopausal status (women). This study was approved by the Institutional Review Board of Fudan university. Inform consent was obtained from each subjects. Declare of Helsinki was followed during the study.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCadmium Determination\u003c/h3\u003e\n\u003cp\u003eThe detailed information on cadmium measurement had been described in our previous study [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Briefly, 1.0 ml of venous blood was collected in tube containing EDTA anticoagulant which was used for the determination of blood cadmium (BCd). 10 ml morning urine was collected for determination of urinary cadmium (UCd) and renal function biomarkers. UCd and BCd were measure by graphite furnace atomic absorption spectrophotometry. The detection limit was 0.05 \u0026micro;g/L.\u003c/p\u003e\n\u003ch3\u003eRenal Function Biomarker And Pth Determination\u003c/h3\u003e\n\u003cp\u003eUrinary N-acetyl-βd-glucosaminidase (UNAG) and urinary albumin (UALB) were selected as renal function biomarkers. The determination methods had been reported in our previous studies [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Briefly, UNAG was determined using a method as described by Tucker et al.(1975). UALB was determined using enzyme-linked immunosorbent assay (ELISA). UCd, UANG and UALB were adjusted with creatinine (cr) and showed as \u0026micro;g/g cr, U/g cr and mg/g cr, respectively.\u003c/p\u003e \u003cp\u003eSerum c-terminal parathyroid hormone (PTH) was assessed by immunoradiometric assay (Beckman, USA). 125I-PTH-M and PTH-M in the serum could competitive bind with antibody. The separation reagent was added. Then the radioactivity count of precipitant was measured (XH-6080, radioimmunoassay counter, China). The radioactivity count was negatively related to the serum PTH levels. The coefficient of variation (CV%) for intra and inter assay is lower than 8%. Urinary phosphates, calcium and creatinine were determined by automatic biochemical analyzer. Low PTH was defined if serum PTH\u0026thinsp;\u0026lt;\u0026thinsp;5 ng/L based on the first quartile of PTH in total population. Serum PTH was determined in 371 subjects (160 in heavy polluted area, 99 in moderate polluted area and 95 in control).\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe data management and analysis was performed by SPSS20.0 (SPSS Inc, Chicago, IL, USA). The continuous data were shown as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD and was compared by Independent-sample T test, or was shown as median (IQR) and was compared by Mann-Whitney U-test. Multivariate logistic regression was adopted to show the association between cadmium levels and PTH. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eCharacteristics of study population\u003c/h2\u003e \u003cp\u003eAfter excluding those subjects with data missing, a total of 354 subjects were included in this study. The characteristics of study subjects is shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The UCd, BCd, UNAG and UALB levels in subjects with low PTH were significant higher than those with PTH\u0026thinsp;\u0026gt;\u0026thinsp;5.0 ng/L (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 or p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). No statistical differences were observed in age, urinary calcium and phosphate level between subjects with low PTH and those with PTH\u0026thinsp;\u0026ge;\u0026thinsp;5.0 ng/L.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of study population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;354)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePTH\u0026thinsp;\u0026lt;\u0026thinsp;5.0 ng/L (n\u0026thinsp;=\u0026thinsp;85)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePTH\u0026thinsp;\u0026ge;\u0026thinsp;5.0 ng/L (n\u0026thinsp;=\u0026thinsp;269)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51.71\u0026thinsp;\u0026plusmn;\u0026thinsp;15.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.3\u0026thinsp;\u0026plusmn;\u0026thinsp;10.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50.4\u0026thinsp;\u0026plusmn;\u0026thinsp;11.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e158.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e158.3\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e158.3\u0026thinsp;\u0026plusmn;\u0026thinsp;7.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60.3\u0026thinsp;\u0026plusmn;\u0026thinsp;10.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCd (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.69 (2.10\u0026ndash;9.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.88 (3.01\u0026ndash;11.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.22 (1.88\u0026ndash;9.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUCd (\u0026micro;g/g cr)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.50 (2.69\u0026ndash;12.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.68 (3.41\u0026ndash;14.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.03 (2.55\u0026ndash;11.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUNAG (U/g cr)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.17 (2.16\u0026ndash;11.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.65 (3.20-11.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.75 (1.81\u0026ndash;10.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUALB (mg/g cr)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.50 (2.08\u0026ndash;10.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.20 (2.50\u0026ndash;13.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.30 (1.90\u0026ndash;9.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTH (ng/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.34 (5.08\u0026ndash;15.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.71 (2.61\u0026ndash;4.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.67 (6.62\u0026ndash;20.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUP (g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.31 (0.19\u0026ndash;0.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.32 (0.22\u0026ndash;0.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.33 (0.20\u0026ndash;0.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUCa (mmol/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.35 (0.22\u0026ndash;0.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.37 (0.25\u0026ndash;0.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.38 (0.22\u0026ndash;0.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eThe Association Between Pth And Cadmium Level\u003c/h3\u003e\n\u003cp\u003eUCd level was negatively correlated to PTH levels (r=-0.17, p\u0026thinsp;=\u0026thinsp;0.008) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). A weak correlation was also observed between BCd and PTH level (r= -0.11, p\u0026thinsp;=\u0026thinsp;0.09).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSubsequently, we showed the association between cadmium level and PTH by logistic regression analysis. BCd and UCd levels were associated with risk of low PTH (odds ratio(OR)\u0026thinsp;=\u0026thinsp;1.04, 95% confidence interval (CI):1.001\u0026ndash;1.07; OR\u0026thinsp;=\u0026thinsp;1.03, 95%CI:1.001\u0026ndash;1.05) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe association between UCd /BCd (continuous data) and low level of PTH\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eModel 2\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCd (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.03 (1.01\u0026ndash;1.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.04 (1.001\u0026ndash;1.07)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.99 (0.97\u0026ndash;1.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.99 (0.97\u0026ndash;1.01)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (female vs male)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.15 (0.70\u0026ndash;1.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.26 (0.74\u0026ndash;2.14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUANG (U/g cr)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.003 (0.99\u0026ndash;1.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.99 (0.97\u0026ndash;1.01)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUALB (mg/g cr)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.01(0.99\u0026ndash;1.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.01 (0.99\u0026ndash;1.03)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUCd (\u0026micro;g/g cr)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.02(1.001\u0026ndash;1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.03 (1.001\u0026ndash;1.05)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.99 (0.97\u0026ndash;1.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.99 (0.97\u0026ndash;1.02)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (female vs male)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.15 (0.70\u0026ndash;1.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.29 (0.76\u0026ndash;2.17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUANG (U/g cr)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.003 (0.99\u0026ndash;1.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.99 (0.97\u0026ndash;1.02)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUALB (mg/g cr)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.01(0.99\u0026ndash;1.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.01 (0.99\u0026ndash;1.04)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eModel 1 Univariable logistic regression analysis\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eModel 2 multivariable logistic regression analysis; model 2 was additionally adjusted with urinary Ca and P levels.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThen we divided the BCd and UCd into categorical data. Univariable and mutivariable logistic regression analysis showed that high BCd (\u0026gt;\u0026thinsp;10 \u0026micro;g/L) (OR\u0026thinsp;=\u0026thinsp;2.26, 95%CI:1.10\u0026ndash;4.63; OR\u0026thinsp;=\u0026thinsp;2.36, 95%CI: 1.11\u0026ndash;5.05) and UCd level (\u0026gt;\u0026thinsp;20 \u0026micro;g/g cr) (OR\u0026thinsp;=\u0026thinsp;2.84, 95%CI:1.32\u0026ndash;6.10; OR\u0026thinsp;=\u0026thinsp;2.97, 95%CI: 1.25\u0026ndash;7.05) were associated with high risk of low PTH (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe association between UCd /BCd (categorical data )and low level of PTH\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eModel1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eModel 2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eModel3\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUCd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.69 (0.91\u0026ndash;3.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.68 (0.90\u0026ndash;3.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.65 (0.88\u0026ndash;3.10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u0026ndash;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.28 (0.65\u0026ndash;2.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.32 (0.67\u0026ndash;2.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.34 (0.67\u0026ndash;2.67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.84(1.32\u0026ndash;6.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.91 (1.27\u0026ndash;8.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.97 (1.25\u0026ndash;7.05)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt; 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u0026ndash;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.29 (0.63\u0026ndash;2.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.27 (0.60\u0026ndash;2.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.21 (0.57\u0026ndash;2.57)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.10 (1.04\u0026ndash;4.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.11(0.99\u0026ndash;4.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.91 (0.88\u0026ndash;4.12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.26(1.10\u0026ndash;4.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.31(1.09\u0026ndash;4.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.36(1.11\u0026ndash;5.05)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eModel 2 was adjusted with age and renal function\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eModel 3 was additionally adjusted with urinary Ca and P levels.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCadmium exposure can cause kidney and bone damage. Severe kidney damage is also a reason for secondary hyperparathyroidism which produce high level of PTH. Hyperparathyroidism could induce excessive bone resroption and result in osteoporosis or bone fracture. We speculated that there may be a link between cadmium exposure and PTH. However, few studies have focused on such association [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Based on ChinaCd study, our data showed that cadmium levels were correlated with serum PTH levels. High BCd or UCd both associated with low PTH levels.\u003c/p\u003e \u003cp\u003eThe association between cadmium exposure and PTH levels have been reported in several animal or epidemiological studies. However, the results are not consistent. Youness et al. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] and Ando et al. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] investigated the impact of cadmium on osteoporosis in rats, and they found that the PTH level in cadmium-treated rats was significantly higher than that in control. A population study in Japan also reported that the PTH level was higher in cadmium-exposed subjects than that in non-exposed individuals [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The sample size in that study is relatively small, only 41 cadmium-exposed subjects and 17 controls. Moreover, the exposure levels may be high because subjects with itai-itai disease were included in this study. Several studies in Europe also showed the association between PTH levels and BCd/UCd in populations with environmental exposure [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Those studies all showed that UCd or BCd level were negatively associated with PTH level. However, those studies were focused on female population. Our study showed that the risk of low PTH increased with the increasing of BCd or UCd. Then we also found that high level of cadmium exposure was associated with low PTH level in total population. Our those findings were consistent with previous European studies. A recent study based on US National Health and Nutrition Examination Survey also showed that BCd was significantly associated with PTH (OR\u0026thinsp;=\u0026thinsp;0.97, 95% CI: 0.95\u0026ndash;0.99 for continuous data; OR\u0026thinsp;=\u0026thinsp;0.94, 95% CI: 0.91\u0026ndash;0.97 for quartile variable).\u003c/p\u003e \u003cp\u003eHow cadmium affect PTH is not completely clarified. Cadmium exposure may result in elevation of serum calcium by inducing excessive bone absroption. The increased bone resorption and high serum calcium would cause a compensatory decrease in PTH [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In addition, cadmium may direct affect the ultrastructure of the parathyroid\u0026ensp;gland [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. High levels of cadmium exposure may affect parathyroid\u0026ensp;gland and inhibit PTH synthesis and secretion. Further studies are needed.\u003c/p\u003e \u003cp\u003eThere are several limitations in our study. First, the threshold for low PTH was based on the first quartile of PTH in total population, not based on clinical cut-off value. Second, we did not show the possible mechanism of cadmium effects on PTH. Third, our study was cross-sectional design. Longitudinal studies may be better to show such association. Finally, serum calcium and phosphate were not determined in this study. But no significant differences were observed in the urinary calcium and phosphate between subjects with low PTH and PTH\u0026thinsp;\u0026ge;\u0026thinsp;5.0 ng/L.\u003c/p\u003e \u003cp\u003eIn conclusion, based on data of ChinaCd study, we showed that BCd and UCd levels were correlated to PTH. Risk of low PTH increased with the increasing of cadmium levels. High level of cadmium exposure caused decrease of serum PTH level.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors declare that there are no conflicts of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by\u0026nbsp;Ethic Committee of\u0026nbsp;Fudan University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInform consent was obtained from each subjects.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCredit author statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJiangchuan Wang: Methodology, Formal Analysis, Writing-Original Draft; Hongye Tang: Methodology, Formal Analysis, Writing-Original Draft; Rongzhou Wang: Methodology, Formal Analysis, Writing-Original Draft; Nandong Hu: Formal Analysis, Writing-Original Draft; Zicheng Wei: Formal Analysis, Writing-Original Draft; Guoying Zhu: Methodology, Formal Analysis, Writing-Review \u0026amp; Editing; Xiao Chen: Conceptualization, Methodology, Formal Analysis, Writing-Original Draft, Writing-Review \u0026amp; Editing; Taiyi Jin: Conceptualization, Methodology, Writing-Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by National Natural Science foundation of China (No. 81773460) and the European Union (Sixth Framework Programme; PHIME; FOOD-CT-2006-016253). The article reflects only the authors\u0026rsquo; views and the European Union is not liable for any use that may be made of the information.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAkesson A, Bjellerup P, Lundh T, Lidfeldt J, Nerbrand C, Samsioe G, Skerfving S, Vahter M (2006) Cadmium-induced effects on bone in a population-based study of women. Environ. Health. Perspect. 114(6): 830\u0026ndash;834.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFilippini T, Michalke B, Malagoli C, Grill P, Bottecchi I, Malavolti M, Vescovi L, Sieri S, Krogh V, Cherubini A, Maffeis G, Modenesi M, Castiglia P, Vinceti M (2016) Determinants of serum\u0026ensp;cadmium\u0026ensp;levels in a Northern Italy community: A cross-sectional study. Environ. Res. 150: 219\u0026ndash;226.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLunyera J, Smith SR (2017) Heavy metal nephropathy: considerations for exposure analysis. Kidney. 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Toxics. 6(1): 15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCunningham J, Locatelli F, Rodriguez M (2011) Secondary hyperparathyroidism: pathogenesis, disease progression, and therapeutic options. Clin. J. Am. Soc. Nephrol. 6(4): 913\u0026ndash;921.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIbrahim KS, Beshir S, Shahy EM, Shaheen W (2016) Effect of Occupational\u0026ensp;Cadmium\u0026ensp;Exposure on\u0026ensp;Parathyroid\u0026ensp;Gland. Open. Access. Maced. J. Med. Sci.4(2): 302\u0026ndash;306.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRignell-Hydbom A, Skerfving S, Lundh T, Lindh CH, Elmst\u0026aring;hl S, Bjellerup P, J\u0026uuml;nsson BA, Str\u0026uuml;mberg U, Akesson A (2009) Exposure to\u0026ensp;cadmium\u0026ensp;and persistent organochlorine pollutants and its association with bone mineral density and markers of bone metabolism on postmenopausal women. Environ. 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Methods. 22(7): 560\u0026ndash;567.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAndo M, Shimizu M, Matsui S, Sayato Y, Takeda M (1987) Influence of\u0026ensp;cadmium\u0026ensp;on the metabolism of vitamin D3 in rats. Toxicol. Appl. Pharmacol. 89(2): 158\u0026ndash;164.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNogawa K, Tsuritani I, Kido T, Honda R, Yamada Y, Ishizaki M (1987) Mechanism for bone disease found in inhabitants environmentally exposed to\u0026ensp;cadmium: decreased serum 1 alpha, 25-dihydroxyvitamin D level. Int. Arch. Occup. Environ. Health. 59(1): 21\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIsono H, Shoumura S, Ishizaki N, Hayashi K, Yamahira T, Yamada S (1979) Effects of\u0026ensp;cadmium\u0026ensp;on the ultrastructure of the mouse\u0026ensp;parathyroid\u0026ensp;gland. Acta. Anat. (Basel). 105(1): 50\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"biological-trace-element-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bter","sideBox":"Learn more about [Biological Trace Element Research](https://www.springer.com/journal/12011)","snPcode":"12011","submissionUrl":"https://submission.nature.com/new-submission/12011/3","title":"Biological Trace Element Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"cadmium, renal dysfunction, parathyroid hormone","lastPublishedDoi":"10.21203/rs.3.rs-2718953/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2718953/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCadmium exposure is associated with renal dysfunction and bone damage. Chronic kidney disease and bone loss are also related to parathyroid hormone (PTH). However, whether cadmium exposure affect PTH level is not completely understood. In this study, we observed the association between environmental cadmium exposure and parathyroid hormone levels in a Chinese population. A ChinaCd study was performed in China in 1990s which included 790 subjects living in heavily, moderately and low cadmium polluted area. 354 of them (121men and 233 women) also had the data of serum PTH. The cadmium levels in blood (BCd) and urine (UCd) were determined by flame atomic absorption spectrometry. Serum PTH was detected by immunoradiometric assay. Renal function was assessed based on urinary N-acetyl-βd-glucosaminidase (UNAG) and urinary albumin (UALB). The median BCd and UCd levels were 4.69 \u0026micro;g/L and 5.50 \u0026micro;g/g creatinine. The BCd, UCd, UNAG and UALB levels in subjects with low PTH (\u0026lt;\u0026thinsp;5.0 ng/L) were significantly higher than those with PTH\u0026thinsp;\u0026ge;\u0026thinsp;5.0 ng/L (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 or p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Spearman correlation analysis also showed that UCd level was negatively correlated to PTH levels (r = -0.17, p\u0026thinsp;=\u0026thinsp;0.008). A weak correlation was also observed between BCd and PTH level (r = -0.11, p\u0026thinsp;=\u0026thinsp;0.09). Univariable and mutivariable logistic regression analysis demonstrated that high BCd (\u0026gt;\u0026thinsp;10 \u0026micro;g/L) (odds ratio (OR)\u0026thinsp;=\u0026thinsp;2.26, 95% confidence interval (CI):1.10\u0026ndash;4.63; OR\u0026thinsp;=\u0026thinsp;2.36, 95%CI: 1.11\u0026ndash;5.05) and UCd level (\u0026gt;\u0026thinsp;20 \u0026micro;g/g cr) (OR\u0026thinsp;=\u0026thinsp;2.84, 95%CI:1.32\u0026ndash;6.10; OR\u0026thinsp;=\u0026thinsp;2.97, 95%CI: 1.25\u0026ndash;7.05) were associated with high risk of low PTH. Our data showed that environmental cadmium exposure was associated with low PTH level.\u003c/p\u003e","manuscriptTitle":"The association between environmental cadmium exposure and parathyroid hormone levels","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-03-23 19:42:34","doi":"10.21203/rs.3.rs-2718953/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2023-03-22T12:29:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-03-22T12:21:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-03-22T00:57:30+00:00","index":"","fulltext":""},{"type":"submitted","content":"Biological Trace Element Research","date":"2023-03-21T14:16:15+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"biological-trace-element-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bter","sideBox":"Learn more about [Biological Trace Element Research](https://www.springer.com/journal/12011)","snPcode":"12011","submissionUrl":"https://submission.nature.com/new-submission/12011/3","title":"Biological Trace Element Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"cf10ebde-5c9f-44c0-8371-edf790e51dd4","owner":[],"postedDate":"March 23rd, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-16T21:01:12+00:00","versionOfRecord":{"articleIdentity":"rs-2718953","link":"https://doi.org/10.1007/s12011-023-03689-x","journal":{"identity":"biological-trace-element-research","isVorOnly":false,"title":"Biological Trace Element Research"},"publishedOn":"2023-05-04 20:40:48","publishedOnDateReadable":"May 4th, 2023"},"versionCreatedAt":"2023-03-23 19:42:34","video":"","vorDoi":"10.1007/s12011-023-03689-x","vorDoiUrl":"https://doi.org/10.1007/s12011-023-03689-x","workflowStages":[]},"version":"v1","identity":"rs-2718953","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2718953","identity":"rs-2718953","version":["v1"]},"buildId":"ApUGefWb6u5IBVtyqm6d5","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}