Serum copper-zinc and copper-selenium ratios in relation to bone health among U.S. adolescents

Adolescence is a critical window for bone development, during which trace elements like copper, zinc, and selenium play essential roles. While previous studies have focused on individual elements, trace element ratios such as the copper-zinc and copper-selenium ratios may better capture biological interactions relevant to bone health.

We used data from the NHANES to examine the association between serum copper-zinc and copper-selenium ratios and whole-body bone mineral density (BMD) among U.S. adolescents. Multivariable linear regression was used to assess associations. Smooth curve fitting visualized dose-response trends. We also compared the strength of associations for ratios and individual elements, and performed mediation and subgroup analyses.

Higher copper-zinc and copper-selenium ratios were significantly associated with lower BMD. Specifically, each one-unit increase in the copper-zinc ratio was associated with a 0.016 g/cm² decrease in BMD (β=-0.016, 95 % CI: -0.026 to -0.006, P = 0.002), while each one-unit increase in the copper-selenium ratio corresponded to a 0.019 g/cm² decrease (β=-0.019, 95 % CI: -0.028 to -0.010, P < 0.001). These associations were stronger than those observed for trace elements alone, especially the copper-selenium ratio. Serum albumin partially mediated the association between these ratios and BMD (mediated proportions: 26.89 % and 14.20 %). Notably, sex-stratified analyses showed significant inverse associations in males, but not in females.

As the first ratio-based NHANES study on adolescent bone health, our analysis shows that serum trace element ratios are inversely associated with BMD, with stronger effects in males. These findings highlight the importance of micronutrient balance in maintaining bone health.