Disentangling the Relationship Between Urinary Metal Exposure and Osteoporosis Risk Across a Broad Population: A Comprehensive Supervised and Unsupervised Analysis

<b>Background</b>: Limited evidence links urinary metal exposure to osteoporosis in broad populations, prompting this study to cover this knowledge gap using supervised and unsupervised approaches. <b>Methods</b>: This study included 15,923 participants from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2020. Urinary concentrations of nine metals-barium (Ba), cadmium (Cd), cobalt (Co), cesium (Cs), molybdenum (Mo), lead (Pb), antimony (Sb), thallium (Tl), and tungsten (Tu)-were measured using inductively coupled plasma mass spectrometry (ICP-MS). Osteoporosis was assessed via dual-energy X-ray absorptiometry. A weighted quantile sum (WQS) regression analysis evaluated each metal's contribution to osteoporosis risk. Partitioning around medoids (PAM) clustering identified the high- and low-exposure groups, and their association with the risk and prognosis of osteoporosis was evaluated. <b>Results</b>: WQS regression identified Cd as a significant osteoporosis risk factor in the general population (odds ratio (OR) = 1.19, 95% confidence interval (CI): 1.08, 1.31, weight = 0.66). Pb notably affected those individuals aged 30-49 years and classified as Mexican American, while Sb impacted Black individuals. PAM clustering showed that the high-exposure group had a significantly higher risk of osteoporosis (OR = 1.74, 95% CI: 1.43, 2.12) and cumulative mortality risk. <b>Conclusions</b>: Urinary metals are associated with the risk and prognosis of osteoporosis.