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The influence of an insulin-like growth factor I gene promoter polymorphism on hip bone geometry and the risk of nonvertebral fracture in the elderly: the Rotterdam Study.

Abstract

The absence of the wildtype allele of a promoter polymorphism of the IGF-I gene is associated with increased risk (1.5; 95% CI, 1.1-2.0) of fragility fracture in women (n = 4212) but not in men (n = 2799). An approximation of hip bone geometry (from DXA) suggested the polymorphism is associated with bone strength and stability in gender-specific ways.

INTRODUCTION

Previously, we found a CA-repeat promoter polymorphism in the insulin-like growth factor I (IGF-I) gene associated with IGF-I levels and BMD in postmenopausal women, but the relationship with fractures is unclear. In this large population-based study of elderly men and women, we examined the association between this IGF-I promoter polymorphism with parameters of bone geometry and the occurrence of fractures.

MATERIAL AND METHODS

Within the Rotterdam Study, a prospective population-based cohort, the IGF-I polymorphism was analyzed in relation to incident nonvertebral fractures in 2799 men and 4212 women followed on average for 8.6 years. Furthermore, we estimated structural parameters of hip bone geometry indirectly from DXA outputs of the femoral neck in 2372 men and 3114 women. We studied neck width, cortical thickness, and the cortical buckling ratio and the section modulus as indexes of bone stability and bending strength.

RESULTS

Women heterozygotes and noncarriers of the allele had, respectively, 1.2 (95% CI, 1.0-1.5) and 1.5 (95% CI, 1.1-2.0) increased risk of having a fragility fracture at older age compared with homozygotes for the 192-bp allele (p trend = 0.0007). In men, fracture risk was not influenced by the polymorphism. Compared with homozygotes for the 192-bp allele, noncarrier males had approximately 1% narrower femoral necks and 2.2% lower section moduli (p trend < 0.05). Noncarrier females had 1.7% thinner cortices and 1.6% higher buckling ratios (p trend < 0.05) but no significant differences in femoral neck widths and section moduli. In women with low body mass index, genotype differences in bone strength (section modulus) and fracture risk were accentuated (p interaction = 0.05). The genotype-dependent differences in hip bone geometry did not fully explain the genotype-dependent differences in fracture risk.

CONCLUSIONS

The CA-repeat promoter polymorphism in the IGF-I gene is associated with the risk for fragility fracture at old age in women and with bone structure in both genders.

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  • Authors+Show Affiliations

    ,

    Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands.

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    Source

    MeSH

    Aged
    Aged, 80 and over
    Body Mass Index
    Bone Density
    Female
    Femur Neck
    Fractures, Bone
    Gene Frequency
    Genotype
    Heterozygote
    Hip Fractures
    Homozygote
    Humans
    Insulin-Like Growth Factor I
    Male
    Middle Aged
    Netherlands
    Pelvic Bones
    Polymorphism, Genetic
    Promoter Regions, Genetic
    Proportional Hazards Models
    Prospective Studies
    Risk Factors
    Sex Factors
    Shoulder Fractures
    Wrist Injuries

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    15231015

    Citation

    Rivadeneira, Fernando, et al. "The Influence of an Insulin-like Growth Factor I Gene Promoter Polymorphism On Hip Bone Geometry and the Risk of Nonvertebral Fracture in the Elderly: the Rotterdam Study." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 19, no. 8, 2004, pp. 1280-90.
    Rivadeneira F, Houwing-Duistermaat JJ, Beck TJ, et al. The influence of an insulin-like growth factor I gene promoter polymorphism on hip bone geometry and the risk of nonvertebral fracture in the elderly: the Rotterdam Study. J Bone Miner Res. 2004;19(8):1280-90.
    Rivadeneira, F., Houwing-Duistermaat, J. J., Beck, T. J., Janssen, J. A., Hofman, A., Pols, H. A., ... Uitterlinden, A. G. (2004). The influence of an insulin-like growth factor I gene promoter polymorphism on hip bone geometry and the risk of nonvertebral fracture in the elderly: the Rotterdam Study. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 19(8), pp. 1280-90.
    Rivadeneira F, et al. The Influence of an Insulin-like Growth Factor I Gene Promoter Polymorphism On Hip Bone Geometry and the Risk of Nonvertebral Fracture in the Elderly: the Rotterdam Study. J Bone Miner Res. 2004;19(8):1280-90. PubMed PMID: 15231015.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The influence of an insulin-like growth factor I gene promoter polymorphism on hip bone geometry and the risk of nonvertebral fracture in the elderly: the Rotterdam Study. AU - Rivadeneira,Fernando, AU - Houwing-Duistermaat,Jeanine J, AU - Beck,Thomas J, AU - Janssen,Joop A M J L, AU - Hofman,Albert, AU - Pols,Huibert A P, AU - Van Duijn,Cornelia M, AU - Uitterlinden,Andre' G, Y1 - 2004/04/12/ PY - 2003/08/21/received PY - 2004/03/10/revised PY - 2004/04/08/accepted PY - 2004/7/3/pubmed PY - 2005/3/17/medline PY - 2004/7/3/entrez SP - 1280 EP - 90 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J. Bone Miner. Res. VL - 19 IS - 8 N2 - UNLABELLED: The absence of the wildtype allele of a promoter polymorphism of the IGF-I gene is associated with increased risk (1.5; 95% CI, 1.1-2.0) of fragility fracture in women (n = 4212) but not in men (n = 2799). An approximation of hip bone geometry (from DXA) suggested the polymorphism is associated with bone strength and stability in gender-specific ways. INTRODUCTION: Previously, we found a CA-repeat promoter polymorphism in the insulin-like growth factor I (IGF-I) gene associated with IGF-I levels and BMD in postmenopausal women, but the relationship with fractures is unclear. In this large population-based study of elderly men and women, we examined the association between this IGF-I promoter polymorphism with parameters of bone geometry and the occurrence of fractures. MATERIAL AND METHODS: Within the Rotterdam Study, a prospective population-based cohort, the IGF-I polymorphism was analyzed in relation to incident nonvertebral fractures in 2799 men and 4212 women followed on average for 8.6 years. Furthermore, we estimated structural parameters of hip bone geometry indirectly from DXA outputs of the femoral neck in 2372 men and 3114 women. We studied neck width, cortical thickness, and the cortical buckling ratio and the section modulus as indexes of bone stability and bending strength. RESULTS: Women heterozygotes and noncarriers of the allele had, respectively, 1.2 (95% CI, 1.0-1.5) and 1.5 (95% CI, 1.1-2.0) increased risk of having a fragility fracture at older age compared with homozygotes for the 192-bp allele (p trend = 0.0007). In men, fracture risk was not influenced by the polymorphism. Compared with homozygotes for the 192-bp allele, noncarrier males had approximately 1% narrower femoral necks and 2.2% lower section moduli (p trend < 0.05). Noncarrier females had 1.7% thinner cortices and 1.6% higher buckling ratios (p trend < 0.05) but no significant differences in femoral neck widths and section moduli. In women with low body mass index, genotype differences in bone strength (section modulus) and fracture risk were accentuated (p interaction = 0.05). The genotype-dependent differences in hip bone geometry did not fully explain the genotype-dependent differences in fracture risk. CONCLUSIONS: The CA-repeat promoter polymorphism in the IGF-I gene is associated with the risk for fragility fracture at old age in women and with bone structure in both genders. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/15231015/The_influence_of_an_insulin_like_growth_factor_I_gene_promoter_polymorphism_on_hip_bone_geometry_and_the_risk_of_nonvertebral_fracture_in_the_elderly:_the_Rotterdam_Study_ L2 - https://doi.org/10.1359/JBMR.040405 DB - PRIME DP - Unbound Medicine ER -