Comparative risk of osteoporotic fractures with direct oral anticoagulants versus vitamin K antagonists in atrial fibrillation patients: a systematic review

Atrial fibrillation (AF) is increasingly prevalent in the elderly population and is associated with an elevated risk of osteoporotic fractures. This systematic review aimed to compare the risk of osteoporotic fractures between direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs), particularly warfarin, in patients with AF and to conduct head-to-head comparisons among different DOACs. We systematically searched literature published between January 2020 and October 2024 across multiple scientific databases. The included studies focused on adult patients with AF taking anticoagulants with fracture outcomes. We extracted and synthesized data on the fracture risk across different anticoagulant types. Our analysis revealed that DOACs, particularly rivaroxaban and apixaban, were associated with a lower fracture risk in AF patients than VKAs. Among the DOACs, apixaban appeared to have the most favorable profile for reducing hip fracture risk. Multiple studies have confirmed that DOACs are associated with decreased vertebral fracture risk compared to warfarin, with risk reductions ranging from 18-32% depending on the specific DOAC. DOACs appear to offer a safer alternative to VKAs in terms of fracture risk in patients with atrial fibrillation. This protective effect may be attributed to their lack of interference with vitamin K-dependent bone metabolism. Although evidence suggests that apixaban and rivaroxaban may have superior bone-protective profiles among DOACs, further research is needed to establish definitive comparisons between individual DOACs and elucidate their protective mechanisms.