Hyojune Kim1,2, Do-Hoon Kim3, Dong Min Kim1, Erica Kholinne1,4, Eui-Sup Lee1, Wael Mohammed Alzahrani1, Ji Wan Kim1, In-Ho Jeon1, Kyoung Hwan Koh1. 1. Department of Orthopaedic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 2. Department of Orthopaedic Surgery, Daejeon Eulji Medical Center, Eulji University School of Medicine, Daejeon, Republic of Korea. 3. Department of Information Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 4. Faculty of Medicine, Universitas Trisakti, Department of Orthopedic Surgery, St. Carolus Hospital, Jakarta, Indonesia.
Abstract
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.
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.