Associations of APOE gene polymorphisms with bone mineral density and fracture risk: A meta-analysis

Summary: To determine the association of the Apolipoprotein E (APOE) E4 gene polymorphism with bone mineral density (BMD) and fractures we conducted a meta-analysis of 17 reports. Despite lower trochanteric and lumbar BMD in APOE4 carriers, there is insufficient evidence to support a consistent association of APOE with bone health. Introduction: APOE has been studied for its potential role in osteoporosis risk. It is hypothesized that genetic variation at APOE locus, known as E2, E3, and E4, may modulate BMD through its effects on lipoproteins and vitamin K transport. The purpose of this study was to determine the association of the APOE-E4 gene polymorphism with bone-related phenotypes. Methods: We conducted a meta-analysis that combined newly analyzed individual data from two community-based cohorts, the Framingham Offspring Study (N=1,495) and the vitamin K clinical trial (N=377), with 15 other eligible published reports. Bone phenotypes included BMD measurements of the hip (total hip and trochanteric and femoral neck sites) and lumbar spine (from the L2 to L4 vertebrae) and prevalence or incidence of vertebral, hip, and other fractures. Results: In sex-pooled analyses, APOE4 carriers had a 0.018 g/cm ² lower weighted mean trochanteric BMD than non carriers (p=0.0002) with no evidence for between-study heterogeneity. A significant association was also detected with lumbar spine BMD (p=0.006); however, inter-study heterogeneity was observed. Associations with lumbar spine and trochanteric BMD were observed predominantly in women and became less significant in meta-regression (p=0.055 and 0.01, respectively). There were no consistent associations of APOE4 genotype with BMD at other skeletal sites or with fracture risk. Conclusions: Based on these findings, there is insufficient evidence to support a strong and consistent association of the APOE genotype with BMD and fracture incidence.