In patients with osteoarthritis, a new study found that the vitamin K antagonist warfarin medication was associated with a significantly increased risk of joint replacement compared with treatment with direct oral anticoagulants.

“Today we have no disease-modifying treatment available, with joint replacement reserved for end-stage disease,” Dr Priyanka Ballal (Boston University Medical Center, USA) stated with regard to osteoarthritis (OA) [1]. She pointed out that vitamin K not only plays a role in coagulation, but that several proteins in bone and cartilage depend on it as well. “Inadequate levels of vitamin K have been shown to cause abnormal joint tissue mineralisation and contribute to the incidence of OA,” she continued to explain. The current study aimed to find out if antagonising vitamin K by warfarin will increase OA progression.

Using data from The Health Improvement Network, a nested case-control study was performed that included 913 patients with knee and hip replacement. These patients were matched by age and gender to 3,652 controls. This UK database contains medical records from general practitioners and is representative of the general population. The sample existed of adults 40-80 years of age between 2009 and 2018 that were treated with warfarin or direct oral anticoagulants (DOAC) for atrial fibrillation. Among the exclusion criteria were severe comorbidities restricting surgery, knee replacement, or hip replacement before 2014 and warfarin or DOAC use within 1 year before the study. By performing a conditional logistic regression, results were controlled for confounders.

Mean age of the study subjects was 75.1 years, 48% were female. Warfarin was given to 64.8% of the cases, while 35.1% received DOAC medication. Among the controls, the rate of warfarin users was 56.3% and 43.6% under DOAC. The results showed that the confounder adjusted risk for knee replacement or hip replacement was 57% higher in the warfarin-treated patients (adjusted odds ratio 1.57, 95% CI 1.30-1.89). Compared to DOAC intake, drug exposure to warfarin augmented the risk over time. A higher risk was still significant in further adjusted analyses that accounted for other reasons for hip replacement than OA. “We then assessed for duration of warfarin use to DOAC use and found an incremental risk of hip replacement and knee replacement with the duration of warfarin use,” Dr Ballal further pointed out. In those with warfarin use over 4 years, the risk of requiring hip replacement or knee replacement was 2-fold.

“Our study implies that given the prevalence and impact of OA, our data along with the existing literature support the need for a well-powered randomised controlled trial for evaluating vitamin K supplementation in OA and our study also raises the consideration of using DOACs over warfarin when indicated in people with or at risk of OA,” Dr Ballal concluded.


  1. Ballal P, et al. Warfarin Use and Risk of Knee and Hip Replacements. S0934, ACR Convergence 2020 Virtual Annual Meeting, 5-9 November 2020.