Osteoporosis International

, Volume 21, Issue 3, pp 457–466

Association between vitamin D receptor gene polymorphisms, falls, balance and muscle power: results from two independent studies (APOSS and OPUS)

  • R. Barr
  • H. Macdonald
  • A. Stewart
  • F. McGuigan
  • A. Rogers
  • R. Eastell
  • D. Felsenberg
  • C. Glüer
  • C. Roux
  • D. M. Reid
Original Article



Fall prevention is a key strategy for reducing osteoporotic fractures. We investigated the association between vitamin D receptor (VDR) polymorphisms and reported falls in postmenopausal women. Bsm1 polymorphisms were associated with falls, balance and muscle power measurements. These results may explain some of the excess fracture risk associated with VDR in some studies.


Fall prevention is a key strategy for reducing osteoporotic fractures. It has been suggested that vitamin D supplementation may reduce the incidence of falls by reducing body sway and increasing muscle power. The vitamin D receptor gene is a well-studied candidate gene for osteoporosis. We investigated the association between VDR polymorphisms and reported falls in postmenopausal women.


Falls data were collected in two separate population cohorts. Five polymorphisms of the VDR gene were analysed (Cdx-2, Fok-1, BsmI, Taq1 and Apa1) in the Aberdeen Prospective Osteoporosis Screening Study (APOSS) cohort. Results found in APOSS were then validated in an independent cohort—the Osteoporosis and Ultrasound (OPUS) study (Bsm1 and Fok1 only), where muscle power and balance were also measured.


Carriers of the ‘B’ allele (Bsm1) showed an increased risk for falls. In APOSS, this was statistically significant for visit 3 multiple falls (p = 0.047) and for recurrent falls (p = 0.043). Similar results were found in OPUS for visit 1 falls (p = 0.025) and visit 1 multiple falls (p = 0.015). Bsm1 polymorphisms were also associated with balance and muscle power measurements.


In conclusion, these results demonstrate an association between the Bsm1 polymorphism and risk of falling that may explain some of the excess fracture risk associated with VDR in some studies.


Balance Falls Muscle power Vitamin D receptor gene 


  1. 1.
    Kanis JA (2002) Diagnosis of osteoporosis and assessment of fracture risk. Lancet 359:1929–1936CrossRefPubMedGoogle Scholar
  2. 2.
    Campbell AJ, Borrie MJ, Spears GF (1989) Risk factors for falls in a community-based prospective study of people 70 years and older. J Gerontol 44:M112–M117PubMedGoogle Scholar
  3. 3.
    Nevitt MC, Cummings SR, Kidd S, Black D (1989) Risk factors for recurrent nonsyncopal falls. A Prospective Study. JAMA 261:2663–2668Google Scholar
  4. 4.
    Robbins AS, Rubenstein LZ, Josephson KR, Schulman BL, Osterweil D, Fine G (1989) Predictors of falls among elderly people. Results of two population-based studies. Arch Int Med 149:1628–1633CrossRefGoogle Scholar
  5. 5.
    Lord SR, Sambrook PN, Gilbert C et al (1994) Postural stability, falls and fractures in the elderly: results from the Dubbo Osteoporosis Epidemiology Study. Med J Aust 160:684–685 688-91PubMedGoogle Scholar
  6. 6.
    Department of Health. How can we help older people not fall again? Implementing the Older People’s NSF Falls Standard: support for commissioning good services. National Service Framework 2003Google Scholar
  7. 7.
    Cummings SR, Nevitt MC (1989) A hypothesis: the causes of hip fractures. J Gerontol 44:M107–M111PubMedGoogle Scholar
  8. 8.
    Lord SR, Clark RD, Webster IW (1991) Visual acuity and contrast sensitivity in relation to falls in an elderly population. Age Ageing 20:175–181CrossRefPubMedGoogle Scholar
  9. 9.
    Fernie GR, Gryfe CI, Holliday PJ, Llewellyn A (1982) The relationship of postural sway in standing to the incidence of falls in geriatric subjects. Age Ageing 11:11–16CrossRefPubMedGoogle Scholar
  10. 10.
    Maki BE, Holliday PJ, Topper AK (1994) A prospective study of postural balance and risk of falling in an ambulatory and independent elderly population. J Gerontol 49:M72–M84PubMedGoogle Scholar
  11. 11.
    Jackson C, Gaugris S, Sen SS, Hosking D (2007) The effect of cholecalciferol (vitamin D3) on the risk of fall and fracture: a meta-analysis. QJM 100:185–192CrossRefPubMedGoogle Scholar
  12. 12.
    Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC et al (2004) Effect of vitamin D on falls: a meta-analysis. JAMA 291:1999–2006CrossRefPubMedGoogle Scholar
  13. 13.
    Pfeifer M, Begerow B, Minne HW, Abrams C, Nachtigall D, Hansen C (2000) Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Miner Res 15:1113–1118CrossRefPubMedGoogle Scholar
  14. 14.
    Janssen HC, Samson MM, Verhaar HJ (2002) Vitamin D deficiency, muscle function, and falls in elderly people. Am J Clin Nutr 75:611–615PubMedGoogle Scholar
  15. 15.
    Pajala S, Era P, Koskenvuo M, Kaprio J, Viljanen A, Rantanen T (2006) Genetic factors and susceptibility to falls in older women. J Am Geriatr Soc 54:613–618CrossRefPubMedGoogle Scholar
  16. 16.
    Onder G, Capoluongo E, Danese P et al (2008) Vitamin D receptor genotype is associated with falls among older adults living in the community: results from the ilSIRENTE study. J Bone Miner Res 23:1031–1036CrossRefPubMedGoogle Scholar
  17. 17.
    Salmen T, Heikkinen AM, Mahonen A et al (2002) Relation of estrogen receptor-alpha gene polymorphism and hormone replacement therapy to fall risk and muscle strength in early postmenopausal women. Ann Med 34:64–72CrossRefPubMedGoogle Scholar
  18. 18.
    Cauley JA, Zmuda JM, Yaffe K, Kuller LH, Ferrell RE, Wisniewski SR, Cummings SR (1997) Apolipoprotein E polymorphism: a new genetic marker of hip fracture risk—the study of osteoporotic fractures. J Bone Miner Res 14:1175–1181CrossRefGoogle Scholar
  19. 19.
    Geusens P, Vandevyver C, Vanhoof J, Cassiman JJ, Boonen S, Raus J (1997) Quadriceps and grip strength are related to vitamin D receptor genotype in elderly nonobese women. J Bone Miner Res 12:2082–2088CrossRefPubMedGoogle Scholar
  20. 20.
    Grundberg E, Brandstrom H, Ribom EL, Ljunggren O, Mallmin H, Kindmark A (2004) Genetic variation in the human vitamin D receptor is associated with muscle strength, fat mass and body weight in Swedish women. Eur J Endocrinol 150:323–328CrossRefPubMedGoogle Scholar
  21. 21.
    Windelinckx A, De Mars G, Beunen G et al (2007) (2007) Polymorphisms in the vitamin D receptor gene are associated with muscle strength in men and women. Osteoporos Int 18:1235–1242CrossRefPubMedGoogle Scholar
  22. 22.
    Vandevyver C, Vanhoof J, Declerck K et al (1999) Lack of association between estrogen receptor genotypes and bone mineral density, fracture history, or muscle strength in elderly women. J Bone Miner Res 14:1576–1582CrossRefPubMedGoogle Scholar
  23. 23.
    Macdonald HM, McGuigan FE, Stewart A et al (2006) (2006) Large-scale population-based study shows no evidence of association between common polymorphism of the VDR gene and BMD in British women. J Bone Miner Res 21:151–162CrossRefPubMedGoogle Scholar
  24. 24.
    Macdonald HM, Mavroeidi A, Barr RJ, Black AJ, Fraser WD, Reid DM (2008) Vitamin D status in postmenopausal women living at higher latitudes in the UK in relation to bone health, overweight, sunlight exposure and dietary vitamin D. Bone 42:996–1003CrossRefPubMedGoogle Scholar
  25. 25.
    Macdonald HM, New SA, Reid DM (2005) Longitudinal changes in dietary intake in Scottish women around the menopause: changes in dietary pattern result in minor changes in nutrient intake. Public Health Nutr 8:409–416CrossRefPubMedGoogle Scholar
  26. 26.
    Gluer CC, Eastell R, Reid DM et al (2004) Association of five quantitative ultrasound devices and bone densitometry with osteoporotic vertebral fractures in a population-based sample: the OPUS Study. J Bone Miner Res 19:782–793CrossRefPubMedGoogle Scholar
  27. 27.
    O’Neill TW, Varlow J, Reeve J et al (1995) Fall frequency and incidence of distal forearm fracture in the UK. J Epidemiol Comm Hlth 49:597–598CrossRefGoogle Scholar
  28. 28.
    Luz Rentero M, Carbonell C, Casillas M, Gonzalez Bejar M, Berenguer R (2008) Risk factors for osteoporosis and fractures in postmenopausal women between 50 and 65 years of age in a primary care setting in Spain: a questionnaire. Open Rheumatol J 2:58–63CrossRefPubMedGoogle Scholar
  29. 29.
    Morrison NA, Qi JC, Tokita A, Kelly PJ et al (1994) Prediction of bone density from vitamin D receptor alleles. Nature 367:284–287CrossRefPubMedGoogle Scholar
  30. 30.
    Kelly PJ, Sambrook PN, Morrison NA, Nguyen T, Eisman JA (1997) Genetics of osteoporosis. World Rev Nutr Diet 80:126–144CrossRefPubMedGoogle Scholar
  31. 31.
    Haussler MR, Whitfield GK, Haussler CA et al (1998) The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res 13:325–349CrossRefPubMedGoogle Scholar
  32. 32.
    Garnero P, Munoz F, Borel O, Sornay-Rendu E, Delmas PD (2005) Vitamin D receptor gene polymorphisms are associated with the risk of fractures in postmenopausal women, independently of bone mineral density. J Clin Endocrinol Metab 90:4829–4835CrossRefPubMedGoogle Scholar
  33. 33.
    Nguyen TV, Esteban LM, White CP et al (2005) Contribution of the collagen I alpha1 and vitamin D receptor genes to the risk of hip fracture in elderly women. J Clin Endocrinol Metab 90:6575–6579CrossRefPubMedGoogle Scholar
  34. 34.
    Styrkarsdottir U, Halldorsson BV, Gretarsdottir S et al (2008) Multiple genetic loci for bone mineral density and fractures. N Engl J Med 358:2355–2365CrossRefPubMedGoogle Scholar
  35. 35.
    Uitterlinden AG, Ralston SH, Brandi ML et al (2006) The association between common vitamin D receptor gene variations and osteoporosis: a participant-level meta-analysis. Ann Intern Med 145:255–264PubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2009

Authors and Affiliations

  • R. Barr
    • 1
  • H. Macdonald
    • 1
  • A. Stewart
    • 1
  • F. McGuigan
    • 1
    • 6
  • A. Rogers
    • 2
  • R. Eastell
    • 2
  • D. Felsenberg
    • 3
  • C. Glüer
    • 4
  • C. Roux
    • 5
  • D. M. Reid
    • 1
    • 7
  1. 1.Bone and Musculoskeletal Research ProgrammeUniversity of AberdeenAberdeenUK
  2. 2.Academic Unit of Bone Metabolism, School of Medicine and Biomedical SciencesUniversity of SheffieldSheffieldUK
  3. 3.Centre Muscle & Bone Research, Charité-Campus Benjamin FranklinFree University and Humboldt UniversityBerlinGermany
  4. 4.Medizinische Physik, Klinik für Diagnostische RadiologieUniversitätsklinikum Schleswig-Holstein, Campus KielKielGermany
  5. 5.Centre d’Evaluation des Maladies Osseuses, Service de Rhumatologie, Hôpital CochinUniversité René DescartesParisFrance
  6. 6.Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences MalmöLund UniversityMalmöSweden
  7. 7.Division of Applied MedicineUniversity of AberdeenAberdeenUK

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