Objective: This study aimed to histologically evaluate the effects of different direct oral anticoagulants (apixaban, rivaroxaban, edoxaban, dabigatran) on healing of standardized bone defects in rat tibias.

Materials and Methods: Forty eight adult Sprague-Dawley rats were randomly assigned to six groups: healthy control, sham control, apixaban, rivaroxaban, edoxaban, and dabigatran (n=8 each group). In all experimental groups, a standardized defect measuring 4 mm in diameter and 4 mm in depth was created in the metaphyseal region of the right tibia. No pharmacological agents were given to the control group, while experimental groups received oral gavage of the respective agents for four weeks at predetermined doses (apixaban 5 mg/kg, rivaroxaban 3 mg/kg, edoxaban 3 mg/kg, dabigatran 10 mg/kg). After four weeks, all rats were euthanized, tibias decalcified and stained with hematoxylin–eosin, and defect areas measured longitudinally and vertically.

Results: A significant difference was found among groups for longitudinal defect area (p=0.019). The rivaroxaban group had a significantly smaller mean longitudinal defect area than the control group (p=0.011). Reductions in other experimental groups were not statistically significant. No significant difference occurred among groups for vertical defect area (p=0.06); however, both dabigatran (p=0.019) and rivaroxaban (p=0.005) groups showed significant reductions compared to control. Rivaroxaban markedly enhanced bone healing in both longitudinal and vertical dimensions, while dabigatran significantly improved vertical healing.

Conclussion: These results suggest certain direct oral anticoagulants may exert beneficial effects on bone regeneration.