Osteoporosis International

, Volume 25, Issue 11, pp 2545–2554 | Cite as

Low serum concentrations of alpha-tocopherol are associated with increased risk of hip fracture. A NOREPOS study

  • K. Holvik
  • C. G. Gjesdal
  • G. S. Tell
  • G. Grimnes
  • B. Schei
  • E. M. Apalset
  • S. O. Samuelsen
  • R. Blomhoff
  • K. Michaëlsson
  • H. E. Meyer
Original Article



We investigated the risk of hip fracture according to circulating alpha-tocopherol, a plant-derived substance with antioxidant properties, in community-dwelling older Norwegians. We found a linear increasing risk of hip fracture with lower serum alpha-tocopherol concentrations, with a 51 % higher risk in the lowest compared to the highest quartile.


Oxidative stress is a suggested contributing cause of osteoporosis and fractures. Vitamin E (α-tocopherol) has potent antioxidant properties in humans. The relationship between circulating α-tocopherol and fracture risk is not established. The aim of this study was to investigate the association between serum α-tocopherol concentrations and risk of hip fracture during up to 11 years of follow-up.


We performed a case-cohort analysis among 21,774 men and women aged 65–79 years who participated in four community-based health studies in Norway 1994–2001. Serum α-tocopherol concentrations at baseline were determined in 1,168 men and women who subsequently suffered hip fractures (median follow-up 8.2 years) and in a random sample (n = 1,434) from the same cohort. Cox proportional hazard regression adapted for gender-stratified case-cohort data was performed.


Median (25, 75 percentile) serum α-tocopherol was 30.0 (22.6, 38.3) μmol/L, and it showed a linear inverse association with hip fracture: hazard ratio (HR) 1.11 (95 % confidence interval (CI) 1.04–1.20) per 10-μmol/L decrease in serum α-tocopherol, adjusted for gender and study center. The lowest compared to the highest quartile conferred an HR of 1.51 (95 % CI 1.17–1.95), adjusted for gender and study center. Adjustment for smoking, month of blood sample, BMI, education, physical inactivity, self-rated health, and serum 25-hydroxyvitamin D (25(OH)D) yielded similar results. Taking serum total cholesterol concentration into account attenuated the association somewhat: HR of hip fracture was 1.37 (95 % CI 1.05–1.77) in first versus fourth quartile of serum α-tocopherol/total cholesterol ratio.


Low serum concentrations of α-tocopherol were associated with increased risk of hip fracture in older Norwegians.


Alpha-tocopherol Case-cohort Hip fracture Norway Vitamin E 



This NOREPOS study was funded by a grant from the Research Council of Norway. The serum sample analyses in HUNT 2 were partly funded by a grant from Central Norway Regional Health Authority. KH’s salary while writing the manuscript was funded by the Norwegian Institute of Public Health. We would like to acknowledge the people involved in carrying out the data collection in Tromsø IV, HUNT 2, HUSK, and HUBRO, those involved in establishing and maintaining the four respective hip fracture follow-up registers, those involved in data management, those involved in biobanks and blood sample handling, and the laboratory AS Vitas, Oslo, Norway, for performing the serum sample analyses. Finally, we would like to thank the participants in the health studies in Norway.

Conflicts of interest

KH, CGG, GST, GG, BS, EMA, SOS, KM, and HEM have nothing to declare. RB has interests in Vitas AS, a company established by Oslo Innovation Center.


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2014

Authors and Affiliations

  • K. Holvik
    • 1
    • 2
  • C. G. Gjesdal
    • 3
    • 4
  • G. S. Tell
    • 2
  • G. Grimnes
    • 5
  • B. Schei
    • 6
  • E. M. Apalset
    • 2
    • 3
  • S. O. Samuelsen
    • 1
    • 7
  • R. Blomhoff
    • 8
    • 9
  • K. Michaëlsson
    • 10
    • 11
  • H. E. Meyer
    • 1
    • 12
  1. 1.Division of EpidemiologyNorwegian Institute of Public HealthOsloNorway
  2. 2.Department of Global Public Health and Primary CareUniversity of BergenBergenNorway
  3. 3.Department of RheumatologyHaukeland University HospitalBergenNorway
  4. 4.Department of Clinical ScienceUniversity of BergenBergenNorway
  5. 5.Tromsø Endocrine Research Group, Department of Clinical MedicineUniversity of TromsøTromsøNorway
  6. 6.Department of Public Health and General PracticeNorwegian University of Science and TechnologyTrondheimNorway
  7. 7.Department of MathematicsUniversity of OsloOsloNorway
  8. 8.Department of Nutrition, Institute of Basic Medical SciencesUniversity of OsloOsloNorway
  9. 9.Division of Cancer, Surgery and TransplantationOslo University HospitalOsloNorway
  10. 10.Department of Surgical Sciences, Section of OrthopedicsUppsala UniversityUppsalaSweden
  11. 11.Uppsala Clinical Research CenterUppsala UniversityUppsalaSweden
  12. 12.Institute of Health and Society, Medical FacultyUniversity of OsloOsloNorway

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