Journal of General Internal Medicine

, Volume 34, Issue 2, pp 304–311 | Cite as

A Systematic Review and Meta-analysis of the Association Between Vitamin K Antagonist Use and Fracture

  • Wendy FiordellisiEmail author
  • Katherine White
  • Marin Schweizer
Review Paper



Vitamin K antagonist (VKA) anticoagulant use is suspected to increase the risk of bone fracture through inhibition of vitamin K–dependent cofactors of bone formation, an effect not seen with non-vitamin K antagonist oral anticoagulants (NOACs). The purpose of our systematic review and meta-analysis is to investigate the association between VKA use and fracture.


We searched PubMed, EMBASE, and Cochrane Library for studies analyzing fracture in adults using VKAs versus controls. Two authors independently reviewed articles. We assessed for risk of bias using the Newcastle-Ottawa Quality Assessment Scale and the Cochrane Risk of Bias Tool and calculated pooled effects using random effects models.


We included 23 articles (22 observational studies and 1 randomized controlled trial), studying 1,121,582 subjects. There was no increased odds of fracture in VKA users versus controls (pooled OR 1.01, 95% CI 0.89, 1.14) or in VKA users versus NOAC users (pooled OR 0.95, 95% CI 0.78, 1.15). Subjects using a VKA for 1 year or longer did not have increased odds of fracture (pooled OR 1.07, 95% CI 0.90, 1.27). Compared to controls, there was increased odds of fracture in women (pooled OR 1.11, 95% CI 1.02, 1.21) and older VKA users (≥ 65) (pooled OR 1.07, 95% CI 1.01, 1.14).


We found no increase in odds of fracture in VKA users versus controls or NOAC users. There was a small increase in odds of fracture among female and elderly VKA users, which may not be clinically important when accounting for other considerations in choosing an anticoagulant. Our findings suggest that, when anticoagulation is necessary, fracture risk should not be a major consideration in choice of an agent. Future studies directly comparing VKA to NOAC users and studies with longer duration of VKA use may be needed.


meta-analysis osteoporosis systematic reviews 



We would like to thank Heather Healy for the assistance with the literature search and Robert Wallace and Rich Hoffman for the assistance with editing the manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they do not have a conflict of interest.

Supplementary material

11606_2018_4758_MOESM1_ESM.docx (31 kb)
ESM 1 (DOCX 31 kb)


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Copyright information

© Society of General Internal Medicine 2018

Authors and Affiliations

  • Wendy Fiordellisi
    • 1
    Email author
  • Katherine White
    • 1
  • Marin Schweizer
    • 1
    • 2
  1. 1.Division of General Internal MedicineUniversity of Iowa Hospitals and ClinicsIowa CityUSA
  2. 2.Department of EpidemiologyUniversity of Iowa College of Public HealthIowa CityUSA

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