Relationship Between the Ratio of Nonhigh‐Density Lipoprotein Cholesterol to High‐Density Lipoprotein Cholesterol and Osteoporosis: The Mediating Role of 25(OH)D and the Moderating Effect of BMI

ABSTRACT Objective To analyse the relationship between the ratio of non‐high‐density lipoprotein cholesterol to high‐density lipoprotein cholesterol (NHHR) and osteoporosis, and explore the mediating role of 25‐hydroxyvitamin D (25(OH)D) and the moderating effect of body mass index (BMI). Methods Four hundred forty‐eight residents selected from ‘REACTION’ cohort study. BMD was measured by dual‐energy X‐ray absorptiometry. Logistic/linear regression and Process models were used to analyse the relationship of NHHR with osteoporosis, 25(OH)D's mediating effect and BMI's moderating effect. Results Logistic regression showed a 42.3% increased osteoporosis risk per 1 unit increase in NHHR (OR = 1.423, p < 0.001) and a 7.6% risk reduction per 1 unit increase in 25(OH)D (OR = 0.924, p < 0.001). Linear regression showed that BMD negatively correlated with NHHR ( β = −0.043, p < 0.001) and positively with 25(OH)D ( β = 0.014, p < 0.001). In addition, 25(OH)D significantly decreased with elevated NHHR ( β = −1.145, p = 0.004). Stratified analysis showed NHHR negatively associated with BMD in all individuals ( p < 0.05), but negatively associated with 25(OH)D only in the overweight and obese. Mediating effect analysis indicated direct (−0.028) and indirect effect (−0.031) effects of NHHR on BMD via 25(OH)D ( p < 0.05). Moderating effect analysis showed a significant negative moderating effect of BMI on the indirect effect of mediation ( p < 0.01). Conclusion NHHR can be used as an early predictor of osteoporosis in middle‐aged and elderly populations. In addition, with increasing BMI, the effect of NHHR on BMD via 25(OH)D diminishes. Therefore, early prevention of osteoporosis should focus not only on lipids but also on vitamin D levels and be stratified according to different BMI levels.