Osteoporosis International

, Volume 27, Issue 4, pp 1645–1652 | Cite as

A combination of low serum concentrations of vitamins K1 and D is associated with increased risk of hip fractures in elderly Norwegians: a NOREPOS study

  • T. E. Finnes
  • C. M. Lofthus
  • H. E. Meyer
  • A. J. Søgaard
  • G. S. Tell
  • E. M. Apalset
  • C. Gjesdal
  • G. Grimnes
  • B. Schei
  • R. Blomhoff
  • S. O. Samuelsen
  • K. Holvik
Original Article



The present study investigated the risk of incident hip fractures according to serum concentrations of vitamin K1 and 25-hydroxyvitamin D in elderly Norwegians during long-term follow-up. The results showed that the combination of low concentrations of both vitamin D and K1 provides a significant risk factor for hip fractures.


This case-cohort study aims to investigate the associations between serum vitamin K1 and hip fracture and the possible effect of 25-hydroxyvitamin D (25(OH)D) on this association.


The source cohort was 21,774 men and women aged 65 to 79 years who attended Norwegian community-based health studies during 1994–2001. Hip fractures were identified through hospital registers during median follow-up of 8.2 years. Vitamins were determined in serum obtained at baseline in all hip fracture cases (n = 1090) and in a randomly selected subcohort (n = 1318). Cox proportional hazards regression with quartiles of serum vitamin K1 as explanatory variable was performed. Analyses were further performed with the following four groups as explanatory variable: I: vitamin K1 ≥ 0.76 and 25(OH)D ≥ 50 nmol/l, II: vitamin K1 ≥ 0.76 and 25(OH)D < 50 nmol/l, III: vitamin K1 < 0.76 and 25(OH)D ≥ 50 nmol/l, and IV: vitamin K1 < 0.76 and 25(OH)D < 50 nmol/l.


Age- and sex-adjusted analyses revealed an inverse association between quartiles of vitamin K1 and the risk of hip fracture. Further, a 50 % higher risk of hip fracture was observed in subjects with both low vitamin K1 and 25(OH)D compared with subjects with high vitamin K1 and 25(OH)D (HR 1.50, 95 % CI 1.18–1.90). The association remained statistically significant after adjusting for body mass index, smoking, triglycerides, and serum α-tocopherol. No increased risk was observed in the groups low in one vitamin only.


Combination of low concentrations of vitamin K1 and 25(OH)D is associated with increased risk of hip fractures.


Case cohort Elderly Hip fracture Osteoporosis Vitamin D Vitamin K1 


Compliance with ethical standards

Conflicts of interest

Trine Elisabeth Finnes, Cathrine Marie Lofthus, Haakon Eduard Meyer, Anne Johanne Søgaard, Grethe S. Tell, Ellen Margrethe Apalset, Clara Gjesdal, Guri Grimnes, Berit Schei, Sven Ove Samuelsen, and Kristin Holvik declare that they have no conflict of interest. Rune Blomhoff has an interest (ownership) in the chemical analysis company Vitas AS (established by the Oslo Innovation Centre)


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2015

Authors and Affiliations

  • T. E. Finnes
    • 1
    • 2
  • C. M. Lofthus
    • 3
  • H. E. Meyer
    • 2
    • 4
  • A. J. Søgaard
    • 4
  • G. S. Tell
    • 5
  • E. M. Apalset
    • 5
    • 6
  • C. Gjesdal
    • 6
    • 7
  • G. Grimnes
    • 8
    • 9
  • B. Schei
    • 10
  • R. Blomhoff
    • 11
    • 12
  • S. O. Samuelsen
    • 4
    • 13
  • K. Holvik
    • 4
  1. 1.Department of Internal MedicineInnlandet Hospital TrustHamarNorway
  2. 2.Institute of Health and Society, Faculty of MedicineUniversity of OsloOsloNorway
  3. 3.Department of EndocrinologyOslo University HospitalOsloNorway
  4. 4.Division of EpidemiologyNorwegian Institute of Public HealthOsloNorway
  5. 5.Department of Global Public Health and Primary CareUniversity of BergenBergenNorway
  6. 6.Department of RheumatologyHaukeland University HospitalBergenNorway
  7. 7.Department of Clinical ScienceUniversity of BergenBergenNorway
  8. 8.Department of Clinical MedicineArctic University of NorwayTromsøNorway
  9. 9.Division of Internal MedicineUniversity Hospital of North NorwayTromsøNorway
  10. 10.Department of Public Health and General Practice NorwegianUniversity of Science and TechnologyTrondheimNorway
  11. 11.Department of Nutrition, Faculty of MedicineUniversity of OsloOsloNorway
  12. 12.Division of Cancer Medicine, Surgery and TransplantationOslo University HospitalOsloNorway
  13. 13.Department of MathematicsUniversity of OsloOsloNorway

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