Evaluation of fracture risk among type 2 diabetes patients with non-valvular atrial fibrillation receiving different oral anticoagulants

Objective: Patients with type 2 diabetes are at higher fracture risk owing to the attenuated bone turnover and impaired bone microarchitecture. The comparative effect of warfarin over non-vitamin K antagonist oral anticoagulants (NOACs) on incident fractures among patients with type 2 diabetes comorbid with atrial fibrillation (AF) remains to be elucidated. Research Design and Methods: This was a retrospective propensity-score weighted population-based cohort study of adults with type 2 diabetes and AF who were started on warfarin or NOAC between 2005 and 2019, identified from the electronic database of the Hong Kong Hospital Authority. The primary outcome was a composite of major osteoporotic fractures (hip, clinical vertebral, proximal humerus and wrist). Hazard ratios (HR) were calculated using Cox proportional hazard regression models. Results: 15,770 type 2 diabetes patients comorbid with AF were included (9,288 on NOAC and 6,482 on warfarin). During a median follow-up of 20 months, 551 patients (3.5%) sustained major osteoporotic fractures (201 in NOAC group [2.2%]; 350 in warfarin group [5.4%]). The adjusted cumulative incidence was lower among NOAC users than warfarin users (HR 0.80, 95% CI 0.64-0.99, p=0.044). Subgroup analyses showed consistent protective effects against major osteoporotic fractures among NOAC users across sex, age, HbA1c, duration of diabetes and history of severe hypoglycemia, compared with warfarin users. Conclusions: NOAC use was associated with a lower risk of major osteoporotic fractures than warfarin use, among type 2 diabetes patients comorbid with AF. NOAC may be the preferred anticoagulant from the perspective of bone health.