TY - JOUR T1 - Vitamin K antagonist anticoagulant usage is associated with increased incidence and progression of osteoarthritis JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 598 LP - 604 DO - 10.1136/annrheumdis-2020-219483 VL - 80 IS - 5 AU - Cindy G Boer AU - Ingrid Szilagyi AU - N Long Nguyen AU - Tuhina Neogi AU - Ingrid Meulenbelt AU - M Arfan Ikram AU - André G Uitterlinden AU - Sita Bierma-Zeinstra AU - Bruno H Stricker AU - Joyce B van Meurs Y1 - 2021/05/01 UR - http://ard.bmj.com/content/80/5/598.abstract N2 - Objectives Vitamin K is hypothesised to play a role in osteoarthritis (OA) pathogenesis through effects on vitamin K-dependent bone and cartilage proteins, and therefore may represent a modifiable risk factor. A genetic variant in a vitamin K-dependent protein that is an essential inhibitor for cartilage calcification, matrix Gla protein (MGP), was associated with an increased risk for OA. Vitamin K antagonist anticoagulants (VKAs), such as warfarin and acenocoumarol, act as anticoagulants through inhibition of vitamin K-dependent blood coagulation proteins. VKAs likely also affect the functioning of other vitamin K-dependent proteins such as MGP.Methods We investigated the effect of acenocoumarol usage on progression and incidence of radiographic OA in 3494 participants of the Rotterdam Study cohort. We also examined the effect of MGP and VKORC1 single nucleotide variants on this association.Results Acenocoumarol usage was associated with an increased risk of OA incidence and progression (OR=2.50, 95% CI=1.94–3.20), both for knee (OR=2.34, 95% CI=1.67–3.22) and hip OA (OR=2.74, 95% CI=1.82–4.11). Among acenocoumarol users, carriers of the high VKORC1(BB) expression haplotype together with the MGP OA risk allele (rs1800801-T) had an increased risk of OA incidence and progression (OR=4.18, 95% CI=2.69–6.50), while this relationship was not present in non-users of that group (OR=1.01, 95% CI=0.78–1.33).Conclusions These findings support the importance of vitamin K and vitamin K-dependent proteins, as MGP, in the pathogenesis of OA. Additionally, these results may have direct implications for the clinical prevention of OA, supporting the consideration of direct oral anticoagulants in favour of VKAs.Data are available upon reasonable request. All relevant data supporting the key findings of this study are available within the article and its supplementary data. Due to ethical and legal restrictions, individual-level data of the Rotterdam Study (RS) cannot be made publicly available. Data are available upon request to the data manager of the Rotterdam Study Frank van Rooij (f.vanrooij@erasmusmc.nl) and subject to local rules and regulations. This includes submitting a proposal to the management team of RS, where upon approval, analysis needs to be done on a local server with protected access, complying with GDPR regulations. ER -