Effect of ketorolac administration on the rate of nonunion of operatively treated humeral shaft fractures: A matched cohort analysis

BACKGROUND: Humeral shaft fractures treated surgically have a 5-10 % risk of nonunion. NSAIDs, including ketorolac, are frequently prescribed postoperatively for pain management, but concerns persist regarding their effects on bone healing. Although prior studies suggest a potential association between ketorolac and nonunion, findings remain inconclusive. This study aims to assess the impact of ketorolac on nonunion risk in adults undergoing surgical treatment for humeral shaft fractures. METHODS: The TriNetX Research Database was queried using ICD and CPT codes to identify patients who underwent operative fixation of humeral shaft fractures with a minimum of 2 years of follow-up. Exclusion criteria included prior humeral shaft nonunion, pathologic fractures, and age under 18. Patients were divided into two cohorts based on whether they received ketorolac within 1 month postoperatively. Outcomes included nonunion diagnosis, nonunion surgery, opioid utilization, wound complications, superficial infection, deep infection, and hardware infection. Outcomes were analyzed at 30 days, 90 days, 1 year, 2 years, and final follow-up. RESULTS: There was no significant difference in opioid utilization within 30 days postoperatively (HR 1.051, 95 % CI 0.987-1.118, p = 0.073; prescriptions 3.2 ± 4.9 vs. 3.2 ± 5.0, p = 0.721). However, at 1-year, 2-year, and overall follow-up, patients receiving ketorolac demonstrated a significantly increased risk of nonunion surgery. At final follow-up (2.9 ± 2.8 years vs. 3.4 ± 3.5 years), nonunion incidence was not significantly different (4.7 % vs. 4.2 %, p = 0.317), but ketorolac use was associated with a 45.1 % increased risk of nonunion surgery (95 % CI 1.050-2.006, p = 0.023). CONCLUSION: Ketorolac use was associated with approximately 40 % increased risk of nonunion surgery without reducing postoperative opioid use. Further research is warranted to evaluate the perioperative administration of ketorolac and other NSAIDs in humeral shaft fractures. LEVEL OF EVIDENCE: Level III Retrospective Cohort Comparison Using Large Database Prognosis Study.