title: Vitamin K antagonists' use and fracture risk: results from a systematic review and meta-analysis.
abstract: BACKGROUND
  Although vitamin K antagonists (VKAs) lower serum values of bone deposition markers, the link with osteoporosis and fractures remains controversial.
  
  
  OBJECTIVE
  To assess whether the use of VKAs is associated with an increased prevalence and/or incidence of osteoporosis, fractures, or lower bone mineral density (BMD) values.
  
  
  METHODS
  We conducted a systematic PubMed and EMBASE literature search until August 31, 2014, and a meta-analysis of cross-sectional and longitudinal studies investigating fractures and BMD, comparing patients treated with VKAs and healthy controls (HCs) or with patients with medical illness (medical controls, MCs). Standardized mean differences ± 95% and confidence intervals (CIs) were calculated for BMD, and risk ratios (RRs) were calculated for prevalent and incident fractures.
  
  
  RESULTS
  Of 4597 initial hits, 21 studies were eligible, including 79 663 individuals treated with VKAs vs. 597,348 controls. Compared with HCs, VKA-treated individuals showed significantly higher fracture risk in cross-sectional (three studies; RR = 1.24; 95% CI: 1.12-1.39, P < 0.0001) and longitudinal studies (seven studies; RR = 1.09; 95% CI: 1.01-1.18, P = 0.03) and more incident hip fractures (four studies; RR = 1.17; 95% CI: 1.05-1.31, P = 0.003). Analyzing studies that matched VKA participants with HCs (four studies), both these findings in longitudinal studies became non-significant. Notably, the VKA and MC group had similar BMD values at all investigated sites. Compared with HCs, a single study showed significantly lower spine T-scores in the VKA-treated group (standardized mean difference = - 0.45; 95% CI: - 0.75, - 0.14, P = 0.004).
  
  
  CONCLUSIONS
  VKAs neither increased prospectively-assessed fracture risk compared with MCs when matching eliminated confounding factors nor reduced BMD beyond effects of medical illness. Future studies, using careful matching and/or adequate MC groups, are needed to further clarify the short- and long-term effects of VKAs on bone health.
authors.affiliation: Department of Medicine, Geriatrics Section, University of Padova, Padova, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Veronese
authors.affiliation: Department of Medicine, Geriatrics Section, University of Padova, Padova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bano
authors.affiliation: Department of Medicine, Geriatrics Section, University of Padova, Padova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bertozzo
authors.affiliation: Department of Medicine, Geriatrics Section, University of Padova, Padova, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Granziera
authors.affiliation: Department of Neurosciences, University of Padova, Padova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Solmi
authors.affiliation: Department of Medicine, Geriatrics Section, University of Padova, Padova, Italy.|National Research Council, Aging Branch, Institute of Neuroscience, Padova, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Manzato
authors.affiliation: Department of Medicine, Geriatrics Section, University of Padova, Padova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Sergi
authors.affiliation: Department of Hematological Medicine, Guys and St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: A T
authors.initials: AT
authors.lastname: Cohen
authors.affiliation: Psychiatry Research, The Zucker Hillside Hospital, North Shore - Long Island Jewish Health System, Glen Oaks, NY, USA.|Hofstra North Shore LIJ School of Medicine, Hempstead, NY, USA.|The Feinstein Institute for Medical Research, Manhasset, NY, USA.|Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: C U
authors.initials: CU
authors.lastname: Correll
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects* / Q000494:pharmacology; D015519:Bone Density / Q000187:drug effects; D015986:Confounding Factors, Epidemiologic; D003430:Cross-Sectional Studies; D005260:Female; D005598:Fractures, Spontaneous / Q000453:epidemiology / Q000209:etiology*; D006620:Hip Fractures / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D064887:Observational Studies as Topic; D010024:Osteoporosis / Q000139:chemically induced* / Q000150:complications / Q000453:epidemiology; D012306:Risk; D012737:Sex Factors; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K
keywords: bone mineral density; coumadin; fractures, bone; hip fractures; osteoporosis