Cadmium Exposure and Osteoporosis: A Population-Based Study and Benchmark Dose Estimation in Southern China

Abstract

This study aimed to assess the association between osteoporosis and long-term environmental Cd exposure through diet in southern China. A total of 1116 subjects from a Cd-polluted area and a non-Cd-polluted area were investigated. All subjects met the criteria of having been living in the investigated area for more than 15 years and lived on a subsistence diet of rice and vegetables grown in that area. Besides bone mineral density, the levels of urinary markers of early renal impairment, such as urinary N-acetyl-β-D-glucosaminidase (NAG), α -microglobulin, β -microglobulin, and urinary albumin, were also determined. Urinary Cd concentrations of all studied subjects ranged from 0.21 to 87.31 µg/g creatinine, with a median of 3.97 µg/g creatinine. Multivariate linear regression models indicated a significant negative association of urinary Cd concentrations with bone mineral density. In logistic regression models, both categorical and continuous urinary Cd concentrations were positively associated with osteoporosis. Subjects in the second, third, and fourth quartiles of urinary Cd concentration had greater odds of osteoporosis compared with subjects in the first quartile (odds ratio [OR] = 3.07, 95% confidence interval [CI], 1.77 to 5.33; OR = 4.63, 95% CI, 2.68 to 7.98; OR = 9.15, 95% CI, 5.26 to 15.94, respectively). Additional adjustment for levels of urinary markers did not attenuate the associations. No evidence existed of an interaction between urinary Cd concentration and renal function using levels of urinary markers, and estimated glomerular filtration rate (eGFR). In all subjects, the benchmark dose and benchmark dose lower bound were 1.14 (0.61) and 2.73 (1.83) µg/g creatinine, with benchmark response set at 5% and 10%, respectively. The benchmark dose of urinary Cd was lower in women than in men. This study demonstrated an inverse association between the body burden of Cd and osteoporosis. The toxic effect of Cd on bone may occur in parallel to nephrotoxicity. © 2017 American Society for Bone and Mineral Research.

Co‐exposure of cadmium and lead on bone health in a southwestern Chinese population aged 40‐75 years

“…In addition, UCd, BCd, UPb and BPb were significantly lower in the unpolluted area, which confirms the Cd and Pb contamination status in the selected study areas. UCd of the population in the unpolluted area in southwestern China in the present study (2.11 μg/g Cr) was a little higher than the UCd levels of the non-Cd-polluted population in southern China (1.70 μg/g Cr) at the same age range reported in Lv et al's study (Lv et al, 2017). However, both UPb and BPb in our study were lower than the levels of UPb and BPb for the control area in the Guizhou province of China (Chen et al, 2014).…”

“…Several epidemiological studies have provided evidence about the associations between reduced BMD, lower T ‐score, higher UCa and higher prevalence of osteoporosis and Cd exposure (Lv et al, ; Nawrot et al, ; Wu et al, ). In the present study, the results of BMD and UCa distribution by Cd quartiles suggested BMD was lower in the upper UCd quartiles, and the excretion of UCa increased with the elevation of UCd quartiles, which were consistent with previous studies.…”

“…During the past decades, a string of observational studies in Belgium, Sweden, Japan, the USA, Korea and China have been conducted and indicated that Cd exposure was related to decreased bone mineral density (BMD) and increased prevalence of osteoporosis (Engström et al, ; Honda et al, ; Kim et al, ; Lv et al, ; Nawrot, Geusens, Nulens, & Nemery, ; Wu, Magnus, & Hentz, ). Furthermore, some studies suggested decreased BMD and increased prevalence of osteoporosis were independent of nephrotoxicity (Callan, Devine, Qi, Ng, & Hinwood, ; Lv et al, ). However, risk assessments and health‐based guidance values for Cd proposed by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) (WHO, ) and the European Food Safety Authority (EFSA) (EFSA, ) were both based on renal toxicity.…”

An assessment of sensitivity biomarkers for urinary cadmium burden

“…The well-known case of the Itai-Itai disease in Japan was the most severe stage of long-term Cd exposure [1]. Many organs are damaged by excess Cd burden, resulting in defective bone formation, including osteoporosis [3,4], and breast cancer [5]. The kidney is an important organ that suffers damage from Cd exposure, as reported by previous studies [6,7].…”

Dietary Intake of Cadmium, Lead and Mercury and Its Association with Bone Health in Healthy Premenopausal Women

“…Cadmium ranks seventh in the Agency for Toxic Substances and Disease Registry (ATSDR) list of elements posing the most significant potential threat to human health in the environment [ 12 ], and both human and in vivo studies have demonstrated cadmium to have toxic effects on bones, resulting in low bone mass, higher risk of osteoporosis and bone fractures [ 13 , 14 , 15 , 16 , 17 , 18 ]. Several population-based studies from Belgium, Sweden, Japan, and China have demonstrated an association between decreased bone mineral density and low-level cadmium exposure [ 15 , 19 , 20 , 21 , 22 ]. Cadmium also interferes with parathyroid hormone stimulation of vitamin D activation in kidney cells to increase urinary excretion of calcium, thereby reducing its absorption from the intestines and interfering with calcium incorporation into bone cells [ 23 ].…”