Risk of new-onset osteoporosis in single-center veteran population receiving direct oral anticoagulants versus warfarin

Oral anticoagulants (OAC) have shown to affect bone mineral density and cause osteoporosis. Limited studies have investigated the relationship between its use and risk of osteoporosis. We aim to compare the risk of osteoporosis in patients on warfarin versus direct oral anticoagulants (DOACs).A retrospective single-center cohort study was conducted in veterans age 18 years of age in whom warfarin or DOACs were newly initiated between January 1st, 2012 to April 1st, 2020 at Salem VA Medical Center. Patients on OAC for at least 90 days qualified for inclusion and excluded if they were pregnant or had history of mechanical valve and mitral stenosis, on edoxaban or had previous history of osteoporosis or use of antiosteoporosis medication. Primary outcome was comparing incidence of new-onset osteoporosis between warfarin and DOACs. Secondary outcomes included comparing incidence of all clinical fractures, hip fractures, major bleeding and intracranial bleed between the treatments. Cox proportional hazard ratios (HRs) and 95% confidence intervals (CI) comparing the two treatment groups were calculated.A total of 1526 patients on DOAC and 1121 in warfarin group were included in the study. After propensity-score (PS) matching, 943 patients were included in each arm. Baseline characteristics were similar after PS-matching. DOAC treatment was associated with lower incidence of new-onset osteoporosis as compared to warfarin in matched cohort (aHR: 0.19, 95% CI: 0.10-0.36; p 0.0001). The risk of all clinical fracture and hip fracture was similar in patients receiving DOACs as versus warfarin (aHR: 1.18, 95% CI: 0.82-1.69; p = 0.3671). DOAC use was associated with lower risk of major bleed (aHR: 0.07, 95% CI: 0.03-0.15; p 0.0001) and intracranial bleed (aHR: 0.14, 95% CI: 0.03-0.64; p = 0.0111).Overall, as compared to warfarin, prolonged use of DOACs is associated with lower risk of new-onset osteoporosis. We hope that our study findings will enlighten current clinical practices assuring safe use of OAC in veteran patients.