Wendy Fiordellisi1, Katherine White2, Marin Schweizer2,3. 1. Division of General Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA. wendy-fiordellisi@uiowa.edu. 2. Division of General Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA. 3. Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA, USA.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). DISCUSSION: 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.
BACKGROUND: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. METHODS: 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. RESULTS: 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). DISCUSSION: 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.
Authors: Gordon H Guyatt; Andrew D Oxman; Regina Kunz; Yngve Falck-Ytter; Gunn E Vist; Alessandro Liberati; Holger J Schünemann Journal: BMJ Date: 2008-05-10
Authors: N Veronese; G Bano; G Bertozzo; S Granziera; M Solmi; E Manzato; G Sergi; A T Cohen; C U Correll Journal: J Thromb Haemost Date: 2015-08-10 Impact factor: 5.824
Authors: Purificacion Rey-Sanchez; Jesus Maria Lavado-Garcia; Maria Luz Canal-Macias; Maria Trinidad Rodriguez-Dominguez; Jose Luis Bote-Mohedano; Juan Diego Pedrera-Zamorano Journal: J Bone Miner Metab Date: 2011-01-14 Impact factor: 2.626
Authors: Wallis C Y Lau; Esther W Chan; Ching-Lung Cheung; Chor Wing Sing; Kenneth K C Man; Gregory Y H Lip; Chung-Wah Siu; Joanne K Y Lam; Alan C H Lee; Ian C K Wong Journal: JAMA Date: 2017-03-21 Impact factor: 56.272
Authors: Pamela L Lutsey; Faye L Norby; Kristine E Ensrud; Richard F MacLehose; Susan J Diem; Lin Y Chen; Alvaro Alonso Journal: JAMA Intern Med Date: 2020-02-01 Impact factor: 21.873