Abstract
Background: The hemoglobin-to-red-cell distribution width ratio has emerged as a novel prognostic marker in various clinical settings. However, its association with total bone mineral density in adolescents remains inadequately explored. Methods: This cross-sectional study was based on data from the 2011-2018 National Health and Nutrition Examination Survey, including adolescents aged 12-19 years with complete data on hemoglobin, red cell distribution width, and total bone mineral density. Weighted multivariable linear regression models and generalized additive models were used to evaluate the association between hemoglobin-to-red-cell distribution width and total bone mineral density. A two-piecewise linear regression model was applied to assess potential threshold effects, with log-likelihood ratio tests used to determine the significance of inflection points. Subgroup and interaction analyses were further conducted to examine whether age, sex, race, and milk product consumption modified this association. Results: A total of 3789 adolescents were included. Participants in the highest hemoglobin-to-red-blood-cell distribution width ratio quartile had significantly higher hemoglobin levels, lower red blood cell distribution width, greater total bone mineral density, higher total calcium and blood urea nitrogen levels, and lower body mass index, high-density lipoprotein cholesterol, and serum 25OHD levels compared to lower quartiles. The hemoglobin-to-red-blood-cell distribution width ratio was positively associated with total bone mineral density (fully adjusted β = 0.078, 95% CI: 0.053, 0.104, p < 0.0001). A two-piecewise linear regression model identified an inflection point at the hemoglobin-to-red-cell distribution width ratio = 1.055; the positive association became stronger above this threshold (β = 0.143 vs. β = 0.039 below the threshold, p = 0.003 for nonlinearity). Subgroup analysis revealed significant gender interactions (p < 0.0001). A higher HRR was significantly associated with greater total BMD in males (β = 0.130, 95% CI: 0.089-0.171, p < 0.0001), whereas no significant association was observed in females (β = -0.009, 95% CI: -0.043-0.025, p = 0.604). Positive associations were also observed among participants aged 12-15 years, non-Hispanic Whites, non-Hispanic Blacks, other Hispanics, Mexican Americans, and frequent milk consumers. Conclusions: Our results indicate that the hemoglobin-to-red-cell distribution width ratio shows a potential association with bone mineral density in male adolescents, which may offer supportive value for bone health assessment but requires further validation.