Role of beta-blockers in fracture healing and nonunion risk in tibial and femoral fractures: A retrospective cohort study using real-world data

Objective Fracture nonunion remains a significant clinical challenge. The inhibitory effects of beta-blockers on ADRB2 signaling may interfere with this process and impair fracture repair. However, their overall impact on bone healing remains unclear. We aimed to investigate the association between beta-blocker use and nonunion risk in patients with tibial and femoral fractures. Methods This retrospective cohort study utilized real-world data from the TriNetX database. Patients aged 40 or older with tibial and femoral fractures treated with intramedullary nailing between 1992 and 2022 were included. Four cohorts were categorized based on beta-blocker use, and propensity score matching (PSM) was applied to construct balanced matched cohorts. The primary analysis used multivariable Cox proportional hazards models, while multivariable logistic regression was performed as a sensitivity analysis. Results In the matched cohort, multivariable Cox regression demonstrated an association between beta-blocker use and increased nonunion risk in tibial fractures (HR = 1.505, 95% CI: 1.177-1.924). Logistic regression sensitivity analysis showed consistent findings (odds ratio [OR] = 1.438, 95% CI: 1.023-2.023). No significant association was observed between beta-blocker use and nonunion risk in femoral fractures. In femoral fractures, nicotine dependence and obesity emerged as stronger risk factors, potentially masking the effects of beta-blockers on fracture healing. Conclusions Beta-blocker use was associated with a moderate likelihood of nonunion in tibial fractures, a finding that may relate to its inhibitory effects on angiogenesis. The association was less pronounced in femoral fractures, likely due to the masking effects of nicotine dependence and obesity. Level of evidence Level III, Prognostic.