Gabapentinoid–Opioid Co-Prescription After Long Bone Fracture Fixation Is Associated with Increased Persistent Opioid Use, Nonunion, and Unplanned Reoperation

Purpose Gabapentinoids are increasingly incorporated into multimodal analgesia after orthopaedic surgery, yet their impact on outcomes following fracture fixation remains unclear. This study evaluated the association between early postoperative gabapentinoid–opioid co-prescription and clinical outcomes after operative fixation of closed long bone fractures. Methods Using the TriNetX Research Network, we identified opioid-naïve and gabapentinoid-naïve adults undergoing intramedullary or plate-and-screw fixation of isolated closed diaphyseal tibia, humerus, or femur fractures. Patients prescribed both gabapentin or pregabalin and opioids within three days after surgery were compared with patients receiving opioids alone. Propensity score matching (1:1) was used to control for demographics, medical comorbidities, fracture location, fixation method, mental health disorders, and substance use disorders. Primary outcomes were prolonged (30–90 days) and chronic (90–180 days) postoperative opioid use. Secondary outcomes included 30-day emergency department (ED) visits and readmissions, and 1-year nonunion and reoperation. Results After matching, each cohort consisted of approximately 2,000 patients (range, 1,946-2,012). Gabapentinoid–opioid therapy was associated with higher rates of prolonged (21.0% vs 16.1%; RR 1.31; p<0.001) and chronic (9.8% vs 7.4%; RR 1.33; p=0.007) postoperative opioid use. Patients receiving gabapentinoid–opioid therapy had fewer 30-day ED visits (25.1% vs 42.5%; RR 0.59; p<0.001), while 30-day readmission rates were similar between groups (p=0.174). One-year rates of nonunion (4.3% vs 1.9%; RR 2.21; p<0.001) and reoperation (7.1% vs 4.2%; RR 1.68; p<0.001) were significantly higher among patients receiving gabapentinoid–opioid therapy. Conclusion Early postoperative gabapentinoid–opioid therapy after long bone fracture fixation was associated with fewer ED visits but substantially higher risks of prolonged and chronic opioid use, nonunion, and the need for reoperation. These findings suggest that potential short-term analgesic benefits may be offset by adverse long-term outcomes, warranting caution and future study in the use of gabapentinoid prescribing to manage acute perioperative fracture pain.