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. 2025 Aug 5;15(1):28583.
doi: 10.1038/s41598-025-12806-w.

L-shaped association of the non-high-density lipoprotein to high-density lipoprotein ratio with low bone mass disorders

Xiaoteng Chen #  1   2 , Wenyi Du #  3 , Hang Li  1   2 , Jian Wang  1   2 , Yinkang Wang  2 , Jijun Zhao  4   5
Affiliations

L-shaped association of the non-high-density lipoprotein to high-density lipoprotein ratio with low bone mass disorders

Xiaoteng Chen et al. Sci Rep. .

Abstract

Osteoporosis and osteopenia, collectively referred to as Low Bone Mass Disorders (LBMD), are characterized by decreased bone density and increased fracture risk. Studies have identified a potential link between cardiovascular disease and LBMD, and the role of lipid metabolism in this has attracted widespread attention. We analyzed participant information collected from multiple NHANES cycles using weighted multivariable logistic regression, subgroup analysis, restricted cubic splines (RCS) curve analysis, and causal mediation analysis. Non-high-density lipoprotein to high-density lipoprotein ratio (NHHR) was significantly negatively associated with low bone mass disorders in a fully adjusted model. We found that NHHR exhibited an L-shaped relationship with the prevalence of LBMD, with a negative association when NHHR < 3.38 and no significant association when NHHR > 3.38. So we could manage both disorders through NHHR. Causal mediation analysis demonstrated that NHHR was a partial mediator of the effect of body mass index (BMI) on low bone mass disorders (LBMD), accounting for 2.3% of the total effect. This suggests that part of the effect in weight affecting low bone mass disorders is mediated by the NHHR. This inspires us to utilize NHHR to guide weight management.

Keywords: BMI; Low bone mass disorders; NHANES; NHHR.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: Data for this study were obtained from the NHANES data builder and ethical approval was obtained from the Ethics Review Board of the Center for Health Statistics.

Figures

Fig. 1
Fig. 1
Flowchart for inclusion and exclusion of NHANES 2005–2010, 2013–2014, and 2017–2020 participants.
Fig. 2
Fig. 2
Weighted Subgroup analysis of the association between NHHR and Low bone mass disorders.
Fig. 3
Fig. 3
Weighted Restricted Cubic Splines (RCS) Curve Fitting. Notes: Subfigure A: Association between NHHR and LBMD without adjusting for confounding factors; Subfigure B: Association between NHHR and LBMD after full adjustment for confounding factors.
Fig. 4
Fig. 4
Mediated analysis model path diagram.Notes: Body mass index was defined as the independent variable; Low bone mass disorders as the dependent variable; and NHHR as the mediating variable. Path a represents the regression coefficient of the association between BMI and NHHR. Path b represents the regression coefficient of the association between NHHR and Low bone mass disorders. Path c represents the simple total effect of NHHR on Low bone mass disorders. Path c’ represents the direct effect of BMI on Low bone mass disorders when controlling for NHHR.
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