| Summary: | Background: Both copper deficiency and overexposure have been associated with adverse health effects. Evidence linking copper to bone mineral density (BMD) and total fracture, however, is limited. Methods: This nationally representative cross-sectional study enrolled participants from the National Health and Nutrition Examination Survey (2011–2014) in the United States. Using unadjusted and multivariate adjusted logistic regression analyses and a two-piecewise linear regression model with a smoothing function, we evaluated the associations between serum copper levels, bone mineral density and total fracture in 722 participants. Results: The study sample (n = 722, mean age: 56.47 ± 11.55 y) represented a population of which 47.2% were men; 43.91% were non-Hispanic white, 18.84% non-Hispanic black and 13.71% Mexican American; 25.9% had total fracture. In the multivariate logistic regression analysis, individuals in the lowest category (<98.5 μg/dL) of serum copper concentration had 0.049 g/cm2 lower total femur BMD and 0.045 g/cm2 lower femoral neck BMD than those in the second concentration category (98.5–114 μg/dL). Individuals in the highest category (≥134 μg/dL) of serum copper concentration had an approximately 4-fold increase in the risk of total fracture than those in the second concentration category. There were no significant associations between per 10 μg/dL increases in serum copper levels and total fracture in multivariate logistic regression analysis after multivariate adjustment (all p > 0.05). However, a differential association between serum copper levels and total fractures between men and women was observed (odds ratio = 1.81, 95% confidence interval 1.08–3.03, p = 0.026 for men and odds ratio = 1.07, 95% confidence interval 0.86–1.32, p = 0.552 for women). Conclusion: Moderate serum copper levels are critically important for bone health. Lower serum copper levels are significantly associated with decreased BMD in the total femur and femoral neck. Higher serum copper levels are significantly associated with increased total fracture, especially in men. The Translational Potential of this Article: The impact of serum copper concentrations on bone mineral density and total fracture can provide insights into clinical application of copper-containing supplements and biomaterials. Keywords: Bone mineral density, Fracture, Odds ratio, Serum copper levels
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