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Do Nonsteroidal Anti-Inflammatory or COX-2 Inhibitor Drugs Increase the Nonunion or Delayed Union Rates After
Hyojune Kim1,2, Do-Hoon Kim3, Dong Min Kim1
1Department of Orthopaedic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Background:
The effects of nonsteroidal anti-inflammatory drugs (NSAIDs)/cyclooxygenase (COX)-2 inhibitors on postoperative fracture-healing are controversial. Thus, we investigated the association between NSAID/COX-2 inhibitor administration and postoperative nonunion or delayed union of fractures. We aimed to determine the effects of NSAID/COX-2 inhibitor administration on postoperative fracture-healing with use of a common data model.
Methods:
Patients who underwent operative treatment of a fracture between 1998 and 2018 were included. To determine the effects of NSAID/COX-2 inhibitor administration on fracture-healing, postoperative NSAID/COX-2 inhibitor users were compared and 1:1 matched to nonusers, with 3,264 patients matched. The effect of each agent on bone-healing was determined on the basis of the primary outcome (nonunion/delayed union), defined as having a diagnosis code for nonunion or delayed union ≥6 months after surgery. The secondary outcome was reoperation for nonunion/delayed union. To examine the effect of NSAIDs/COX-2 inhibitors on bone union according to medication duration, a Kaplan-Meier survival analysis was performed.
Results:
Of the 8,693 patients who were included in the analysis, 208 had nonunion (178 patients; 2.05%) or delayed union (30 patients; 0.35%). Sixty-four (30.8%) of those 208 patients had a reoperation for nonunion or delayed union. NSAID users showed a significantly lower hazard of nonunion compared with the matched cohort of nonusers (hazard ratio, 0.69 [95% confidence interval, 0.48 to 0.98]; p = 0.040) but did not show a significant difference in the other matched comparison for any other outcomes. Kaplan-Meier survival analysis revealed significantly lower and higher nonunion/delayed union rates when the medication durations were ≤3 and >3 weeks, respectively (p = 0.001). For COX-2 inhibitors, the survival curve according to the medication duration showed no significant difference among the groups (p = 0.9).
Conclusions:
Our study demonstrated no short-term impact of NSAIDs/COX-2 inhibitors on long-bone fracture-healing. However, continued use of these medications for a period of >3 weeks may be associated with higher rates of nonunion or delayed union.
Level Of Evidence:
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Insights
Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX)-2 inhibitors show no short-term impact on fracture healing. However, extended use beyond three weeks may increase risks of nonunion or delayed union.
Area of Science:
- Orthopedic Surgery
- Pharmacology
- Biomedical Engineering
Background:
- The impact of nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors on fracture healing remains debated.
- Investigating the association between NSAID/COX-2 inhibitor use and postoperative fracture complications like nonunion or delayed union is crucial.
Purpose of the Study:
- To determine the effects of NSAID/COX-2 inhibitor administration on postoperative fracture healing.
- To analyze the association between medication duration and fracture union outcomes.
Main Methods:
- A retrospective cohort study included 8,693 patients undergoing operative fracture treatment from 1998 to 2018.
- Patients were 1:1 matched between NSAID/COX-2 inhibitor users and nonusers (3,264 pairs).
- Outcomes included nonunion/delayed union (≥6 months post-surgery) and reoperation rates, analyzed using Kaplan-Meier survival analysis.
Main Results:
- NSAID users exhibited a significantly lower hazard of nonunion compared to nonusers (HR 0.69, p=0.040).
- Kaplan-Meier analysis showed significantly lower nonunion/delayed union rates for medication durations ≤3 weeks and higher rates for durations >3 weeks (p=0.001).
- No significant difference in outcomes was observed for COX-2 inhibitors based on medication duration.
Conclusions:
- NSAIDs/COX-2 inhibitors demonstrate no short-term adverse effects on long-bone fracture healing.
- Prolonged use (>3 weeks) of these medications may be linked to increased rates of fracture nonunion or delayed union.
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