Testosterone replacement therapy increases the risk of nonunion after surgical fixation of lower extremity fractures

Testosterone replacement therapy (TRT) impacts bone mineral density and has been suggested to impact bone remodeling, yet its effects on fracture healing have not been completely characterized.

A large-scale, multicenter retrospective cohort analysis was conducted utilizing a national database. Adult male patients who underwent surgical fixation for lower extremity fractures between 2005 and 2025 with a minimum of 2 years of follow-up were included. Patients were stratified into TRT and control cohorts based on documented use of testosterone replacement therapy, with 9067 patients in the TRT cohort and 88,510 in the control group. Following multivariate propensity score matching, 9027 patients were collated to each cohort. Statistical analyses included risk ratios (RR), confidence intervals (CI), and p-values, calculated using Student's t-tests and chi-square tests.

At two years, TRT patients demonstrated significantly elevated risks for nonunion (RR 1.172, p = 0.017) and revision (RR 1.329, p = 0.003). No significant differences were observed in deep vein thrombosis, pulmonary embolism or wound complications between the cohorts.

Testosterone replacement therapy (TRT) increases bone healing complications following surgical fixation of lower extremity fractures which was also associated with greater revision surgeries for nonunion repair. However, thromboembolic events as well as wound complications were not associated with testosterone supplementation. These findings highlight the need for study into preoperative TRT as a risk factor for adverse outcomes in orthopedic trauma surgery.