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No Association Between Hip Geometry and Four Common Polymorphisms Associated with Fracture: The Danish Osteoporosis Prevention Study

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Abstract

Both osteoporosis and hip geometry are independently associated with fracture risk. There is a significant genetic contribution to the risk of osteoporosis, and evidence provided by twin studies has suggested that hip geometry may also in part be genetically programmed. Polymorphisms in a number of genes, including those coding for methylene-tetrahydrofolate reductase (MTHFR c.677C > T), the purinergic P2X7 receptor (Glu496Ala and Ile568Asn), and the low-density lipoprotein receptor–related protein 5 (LRP5 exon 9 [c.266A > G]), have been associated with an increased fracture incidence and/or reduced bone mineral density (BMD). The aim of the present study was to test whether these polymorphisms influence hip structural geometry in perimenopausal women. The four polymorphisms were genotyped in 800 healthy recently perimenopausal women never using hormone replacement therapy. BMD of the femoral neck was measured using a Hologic® QDR-2000 densitometer and femoral neck axis length, neck width, neck shaft angle, and femoral head diameter were measured from the screen images. Genotype frequencies were compatible with Hardy–Weinberg equilibrium. No significant differences between homozygotes for the minor allele and carriers of the common allele regarding parameters of hip geometry were demonstrated. According to the anthropometric characteristics of the subjects, only body height in the MTHFR TT genotype group was significantly different from the combined CT/CC genotype group (P < 0.05). The geometric dimensions of the proximal femur in perimenopausal women are not associated with the MTHFR c.677C > T, P2X7 (Glu496Ala), P2X7 (Ile568Asn), and LRP5 exon 9 (c.266A > G) polymorphisms.

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Acknowledgments

Kirsten Westermann, Donna Arbuckle-Lund, Anette Riis Madsen, Liselotte Stenkjaer, Mette Carstens, Gunhild Andreasen, Solveig Petersen, and Stine Ohlendorff are thanked for excellent technical assistance. Financial support from the Karen Elise Jensen Foundation and Novo Nordisk Farmaka (Lyngby, Denmark) is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Endocrinology, Odense University Hospital, University of Southern Denmark, Odense, 5000, Odense C, Denmark

    N. Nissen & K. Brixen

  2. Department of Biochemistry, Pharmacology, and Genetics, Odense University Hospital, University of Southern Denmark, Odense, 5000, Odense C, Denmark

    J. S. Madsen

  3. Unit for Thrombosis Research, Institute of Public Health, University of Southern Denmark, 6700, Esbjerg, Denmark

    E. M. Bladbjerg

  4. Department of Clinical Biochemistry, Hospital of Southwest Denmark, 6700, Esbjerg, Denmark

    E. M. Bladbjerg

  5. Osteoporosis Research Clinic, Hvidovre University Hospital, 2650, Hvidovre, Denmark

    J. E. Beck Jensen & N. R. Jørgensen

  6. Department of Endocrinology, Aarhus Amtssygehus, Aarhus University Hospital, 8000, Aarhus C, Denmark

    B. Langdahl

  7. Department of Internal Medicine F, Gentofte Hospital, 2900, Hellerup, Denmark

    B. Abrahamsen

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  1. N. Nissen
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Nissen, N., Madsen, J.S., Bladbjerg, E.M. et al. No Association Between Hip Geometry and Four Common Polymorphisms Associated with Fracture: The Danish Osteoporosis Prevention Study. Calcif Tissue Int 84, 276–285 (2009). https://doi.org/10.1007/s00223-009-9219-9

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