The Association of Lipids and Lipoproteins with Hip Fracture Risk: The Cardiovascular Health Study

Abstract

Background: It is uncertain if lipids or lipoproteins are associated with osteoporotic fractures. In this study, incident hip fracture risk according to conventional lipid levels and lipoprotein levels and sizes was examined.

Methods: We followed 5832 participants aged ≥65 years from the Cardiovascular Health Study for hip fracture for a mean of 13.5 (SD 5.7) years. Standard enzymatic methods were used to determine lipid levels (ie, high-density lipoprotein-cholesterol [HDL-c], low-density lipoprotein-cholesterol [LDL-c], and triglycerides). Nuclear magnetic resonance spectroscopy was used to measure lipoprotein fractions (ie, very-low-density lipoprotein-particle [VLDL-P], low-density lipoprotein-particle [LDL-P], high-density lipoprotein-particle [HDL-P]) in a subset of 1849 participants.

Results: We documented 755 incident hip fractures among women (1.19 fractures per 100 participant years [95% confidence interval, 1.04, 1.35]) and 197 among men (0.67 fractures per 100 participant years [95% CI, 0.41, 1.10]) over an average follow-up. HDL-c and LDL-c levels had statistically significant nonlinear U-shaped relationships with hip fracture risk (HDL-c, P = .009; LDL-c, P = .02). Triglyceride levels were not significantly associated with hip fracture risk. In fully adjusted conjoint models, higher VLDL-P concentration (hazard ratio [HR] per 1 standard deviation [SD] increment 1.47 [1.13, 1.91] and size [HR per 1 SD increment 1.24 [1.05, 1.46]) and higher high-density lipoprotein particle size (HR per 1 SD increment 1.81 [1.25, 2.62]) were all associated with higher hip fracture risk.

Conclusions: Lipids and lipoproteins are associated with hip fracture risk in older adults. The associations are complex. Mechanistic studies are needed to understand these findings.

Keywords: Hip fracture; Lipid; Lipoprotein particle.

Figure 1:

Generalized additive models with splines for winsorized lipid levels in M2 in a single model. W = winsorized.

Figure 2:

Generalized additive models with splines for winsorized lipoprotein particle levels and sizes in M2 in a single model. VLDLP – VLDL particle concentration. VZ – VLDL particle size. LDLP – LDL particle concentration. LZ - LDL particle size. HDLP – HDL particle concentration. HZ – HDL particle size. W- winsorized.