Study: Possible Link Between Long-Term Warfarin Use and Ankle Fracture Nonunion

A recent retrospective study conducted by researchers from Kaiser Permanente Northern California (KPNC) points to a potential association that may influence clinical decisions when managing patients with traumatic ankle fractures who are also on chronic anticoagulation therapy.

Warfarin, a widely prescribed Vitamin K antagonist, interferes with the activation of two Vitamin K-dependent proteins that are essential for bone mineralization and the activation of bone morphogenetic proteins—factors critical for bone healing. This study evaluated plausibility of impaired fracture healing linked to warfarin in the context of ankle fractures.

The study, presented at the American College of Foot and Ankle Surgeons 2025 Scientific Conference, reviewed cases from 2017 to 2021, analyzing data from 610 adult KPNC members with ankle fractures. Among these, 122 patients experienced nonunion, and they were compared to 488 matched union controls in a 1:4 ratio based on race, body mass index, and age. Exclusion criteria included open fractures and infections to control for potential confounding factors. Additional covariates analyzed included sex, diabetes mellitus, osteoporosis, vitamin D deficiency, alcohol use, tobacco use, vitamin D supplementation, and steroid use. Statistical analyses were performed using Wilcoxon and Fisher’s Exact tests to determine differences between groups.

The proportion of nonunion was higher among warfarin users (29.4%) compared with non-users (19.7%), but this difference did not reach statistical significance (P = .354). Four out of the five nonunion cases in the Warfarin group were on the anticoagulant for more than 6 months, suggesting a potential link between duration of therapy and fracture healing outcomes.

While the study stops short of confirming a definitive association, the observed trend suggests that long-term warfarin use could adversely affect fracture healing, warranting further investigation.

“Future studies can help direct care for patients with ankle fracture and long-term warfarin use,” the study authors concluded.

Reference:
Hoque T, Fink D, Bowlby M. Impact of Vitamin K antagonist Warfarin on ankle fracture healing. Presented at: American College of Foot and Ankle Surgeons 2025 Scientific Conference; March 27-30, 2025; Phoenix, AZ. Accessed March 6, 2025. https://imis.acfas.org/ACFAS2025/ACFAS2025/Abstracts.aspx