APOE 4 and hip fracture risk in a community-based study of older adults

OBJECTIVES: To investigate whether the APOE 4 allele was associated with increased risk of hip fracture in an older community-based sample and whether such an increased risk was independent of dementia and history of falling. DESIGN: Case-central study nested within a prospective community study. SETTING: The Monongahela Valley Independent Elders Survey (MoVIES), an ongoing prospective community study of older adults in southwestern Pennsylvania. PARTICIPANTS: A total of 899 MoVIES participants (63.9% women; mean age, 76.2 years, SD = 4.9 years), who provided both information on hip fractures and blood samples for genotyping. MEASUREMENTS: Interview questions regarding hip fractures and falls, polymerase chain reaction to determine APOE genotype, and clinical assessment using a standardized protocol to determine the presence or absence of dementia. RESULTS: Twenty-live subjects reported having hip fractures in the year preceding screening interviews. Subjects with one or two APOE 4 alleles were twice as likely as subjects without an APOE 4 allele to report hip fractures (age-adjusted OR = 2.1, 95% CI: 0.9-4.7). Based on multivariate analysis, subjects with a history of falling were more likely to report hip fractures (OR = 4.7, 95% CI: 2.1-10.8). After adjusting for history of falls and diagnosis of dementia, subjects with an APOE 4 allele were still twice as likely to report hip fractures (adjusted OR = 2.1, 95% CI: 0.9-4.7). CONCLUSIONS: The APOE 4 allele appears to be a risk factor for hip fracture, independent of the effect of dementia and falling. Theoretically, this may be mediated by alterations in vitamin K metabolism. Caution should be used in interpreting these results, because the 95% confidence intervals for the odds ratios include 1.