Vitamin K antagonist anticoagulant usage is associated with increased incidence and progression of osteoarthritis
Cindy G. Boer, I Szilágyi, Nhu Nguyen, Tuhina Neogi, Ingrid Meulenbelt, M. Arfan Ikram, André G. Uitterlinden, Sita Bierma‐Zeinstra, Bruno H. Stricker, Joyce B. J. van Meurs
Abstract
<h3>Objectives</h3> 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. <h3>Methods</h3> 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 <i>MGP</i> and <i>VKORC1</i> single nucleotide variants on this association. <h3>Results</h3> 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 <i>VKORC1(BB</i>) expression haplotype together with the <i>MGP</i> 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). <h3>Conclusions</h3> 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.