Abstract
Emerging evidence suggests that lipid metabolism plays a critical role in bone homeostasis. The ratio of remnant cholesterol/high-density lipoprotein cholesterol (RC/HDL-C) has recently been proposed as a novel indicator of metabolic risk; however, its relationship with bone mineral density (BMD) remains unclear. This study aimed to explore the association between RC/HDL-C and total BMD in a nationally representative population. Data were derived from the 2011-2018 National Health and Nutrition Examination Survey, including 3688 US adults aged 20 to 59 years. The RC/HDL-C ratio was calculated as (total cholesterol - HDL-C - low-density lipoprotein cholesterol)/HDL-C. Total BMD was measured using dual-energy x-ray absorptiometry. Multivariable linear regression models were used to examine the association between RC/HDL-C and BMD, adjusting for demographic, lifestyle, and clinical covariates. Nonlinear associations were explored via smooth curve fitting and threshold effect analyses. Subgroup and interaction analyses were also conducted. A significant inverse association was observed between RC/HDL-C and total BMD. After full adjustment, each 1-unit increase in RC/HDL-C was associated with a 0.019 g/cm² decrease in BMD (β = -0.019; 95% confidence intervals (CI): -0.027 to -0.010; P < .0001). Quartile analysis revealed a dose-response relationship, with the highest quartile showing the strongest negative association (β = -0.029; 95% CI: -0.039 to -0.020; P < .0001). A nonlinear relationship was identified, with an inflection point at 0.677; below this value, the negative association was more pronounced (β = -0.049; 95% CI: -0.068 to -0.030; P < .0001). Subgroup analyses confirmed consistent associations across most groups, and a significant interaction was found with smoking status (P for interaction .05). RC/HDL-C was inversely associated with BMD, with stronger associations observed in smoking status. These findings highlight the RC/HDL-C ratio as a potential predictor for bone health risk stratification and warrant further investigation in longitudinal and mechanistic studies.