Frontiers in Public Health · 6 authors, 3 centres
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This study analyzed NHANES data from 1,777 middle-aged and older US adults and found that higher blood cadmium levels were strongly associated with increased osteoporosis prevalence, while higher blood selenium levels appeared protective. The findings suggest that environmental heavy metal exposure may be a modifiable risk factor for osteoporosis in aging populations.
**Background:** Osteoporosis is a systemic metabolic disease affecting over 10 million US adults aged 50+ as of 2010, with projections reaching 13.5 million by 2030. Characterized by bone mineral density (BMD) loss and increased fracture risk, osteoporosis imposes substantial economic and medical burdens. While traditional risk factors include older age and female gender, emerging evidence suggests heavy metal exposure may contribute to bone deterioration through mechanisms including increased bone resorption, altered hormone metabolism, and oxidative stress. Previous studies on heavy metals and osteoporosis have been limited by small sample sizes or reliance on urinary rather than blood measurements.
**Methods:** This secondary analysis used data from NHANES 2013–2014 and 2017–2018. From an initial 19,429 participants, exclusions were made for incomplete heavy metal data (N=7,330), missing BMD data (N=8,347), age below 40 years, and missing basic information, yielding 1,777 participants (115 with osteoporosis, 1,662 without). BMD was measured at four femoral regions (total femur, femur neck, trochanter, intertrochanter) using DXA with Hologic QDR-4500A densitometers. Osteoporosis was defined per WHO criteria as BMD ≥2.5 SD below young adult mean. Blood heavy metals (Pb, Cd, Hg, Se, Mn) were measured by inductively coupled plasma mass spectrometry. Covariates included demographics, BMI, smoking, alcohol, physical activity, comorbidities (diabetes, hypertension, arthritis, thyroid problems, hypercholesterolemia), GFR, and household income. Logistic regression with survey weights was used across three models: Model 1 adjusted for age, gender, race; Model 2 additionally adjusted for education, BMI, arthritis, thyroid problems, GFR, income; Model 3 further adjusted for smoking, diabetes, hypertension, physical activity, alcohol, secondhand smoke, sedentary behavior, hypercholesterolemia. Weighted quantile sum (WQS) regression assessed mixture effects.
**Key Results:** The weighted average age was 58.9±0.4 years, with 50.4% men. Osteoporosis participants were older (66.9 vs. 58.4 years), more likely female (74.8% vs. 48.0%), had lower BMI, higher arthritis prevalence (53.1% vs. 38.5%), more thyroid problems (24.7% vs. 15.9%), lower GFR, and lower income. Blood cadmium showed a strong, dose-dependent positive association with osteoporosis across all models. In Model 1: Q2 OR=7.62 (95% CI 2.01–29.03, p=0.003); Q3 OR=12.38 (95% CI 3.88–39.60, p<0.001); Q4 OR=15.64 (95% CI 3.22–76.08, p=0.001). Results remained significant in fully adjusted Model 3 (Q4 OR=17.98, 95% CI 2.54–127.07, p=0.004). Blood selenium showed a protective effect: Model 1 Q4 OR=0.34 (95% CI 0.14–0.39, p<0.001); Model 3 Q4 OR=0.26 (95% CI 0.15–0.45, p<0.001). Lead, mercury, and manganese showed no consistent significant associations. WQS analysis confirmed cadmium as the primary positive contributor and selenium as the primary negative contributor to osteoporosis risk. Subgroup analysis revealed the cadmium-osteoporosis association was significant in women (Model 3: Q2 OR=14.11, Q3 OR=30.55, Q4 OR=27.00) but not in men. Selenium's protective effect was observed in both sexes and in both smoking and non-smoking subgroups. The cadmium association persisted in non-smokers but was not significant in smokers.
**Clinical Implications:** This large, population-based study provides evidence that blood cadmium is independently and strongly associated with higher osteoporosis prevalence in a dose-dependent manner, particularly among women, while selenium may exert a protective effect. These findings suggest that environmental cadmium exposure could be a modifiable risk factor for osteoporosis in aging populations. Clinicians should consider heavy metal exposure history, especially in postmenopausal women with osteoporosis. The protective role of selenium warrants further investigation as a potential nutritional intervention. However, the cross-sectional design precludes causal inference, and residual confounding cannot be excluded. Prospective studies are needed to confirm these relationships and elucidate underlying mechanisms, including cadmium's effects on bone marrow mesenchymal stem cells via NF-κB and P2X7-PI3K-AKT pathways, and selenium's role in osteoblastic differentiation through oxidative stress regulation.