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UNLABELLED: To study the association between the ApoE gene polymorphism and osteoporosis, we performed an association study in 5,857 subjects from the Rotterdam Study. We did not observe an association between the ApoE polymorphism and osteoporosis in this study, which is thus far the largest study on ApoE and osteoporosis. INTRODUCTION: The E*4 allele of the E*2, E*3, E*4 protein isoform polymorphism in the gene encoding apolipoprotein E (ApoE) has previously been associated with an increased fracture risk. We investigated the association between the ApoE polymorphism and BMD, bone loss, and incident fractures as part of the Rotterdam Study a prospective population-based cohort study of diseases in the elderly. MATERIALS AND METHODS: The study population consisted of 5,857 subjects (2,560 men; 3,297 women) for whom data on ApoE genotypes, confounding variables, and follow-up of nonvertebral fractures were available. Data on femoral neck and lumbar spine BMD were available for 4,814 participants. Genotype analyses for bone loss (defined as annualized percent change in BMD at the hip and lumbar spine) and BMD were performed using ANOVA. Fractures were analyzed using a Cox proportional-hazards model and logistic regression. All relative risks were adjusted for age and body mass index. RESULTS AND CONCLUSIONS: The genotype distribution of the study population was in Hardy-Weinberg equilibrium (p = 0.98) and did not differ by gender. At baseline, mean BMD of the lumbar spine and femoral neck did not differ between the ApoE genotypes of men and women. Bone loss (mean follow-up, 2.0 years) did not differ by ApoE genotype for women and men. During a mean follow-up of 6.6 years, 708 nonvertebral fractures (198 hip fractures and 179 wrist fractures) and 149 incident vertebral fractures occurred. No consistent differences in the distribution of alleles could be observed between subjects with or without these fractures. Our data do not support the hypothesis that the ApoE*4 risk allele is associated with BMD, increased bone loss, or an increased risk of osteoporotic fractures.

Original publication




Journal article


J Bone Miner Res

Publication Date





1490 - 1496


Aged, Alleles, Apolipoproteins E, Body Mass Index, Bone Density, Cohort Studies, Female, Femur Neck, Fractures, Bone, Gene Frequency, Genotype, Humans, Lumbar Vertebrae, Male, Osteoporosis, Polymorphism, Genetic, Prospective Studies, Risk