Urinary cadmium in relation to bone damage: Cadmium exposure threshold dose and health-based guidance value estimation

Cadmium (Cd) is a widespread heavy metal with osteotoxicity, and bone mineral density (BMD) is often used as an early sensitive biomarker of bone damage. This study retrieved worldwide epidemiological studies to conduct a systematic meta-analysis to explore the association between Cd exposure and bone damage. A random effect model was used to establish the relationship between urinary Cd (U-Cd) and BMD and explore the influence of covariate factors. The benchmark dose method was used to calculate the safety threshold of U-Cd when the BMD decrease within an acceptable range. Toxicokinetic (TK) model was used to estimate the health-based guidance value (HBGV) of dietary Cd exposure based on the U-Cd threshold. The 95% lower confidence interval of benchmark dose of U-Cd derived in this study was 1.71 μg/g Cr, and the HBGV of dietary Cd exposure was determined to be 0.64 μg/kg bw/day. Gender had the greatest influence on BMD, followed by body mass index (BMI), age, and race. This study conducted a comprehensive systematic analysis of global research and was the first exploration to quantify the decreased BMD caused by Cd exposure in a large-scale population. The results provided reference for the risk assessment of Cd exposure and the formulation of dietary exposure standards.