Although ibuprofen has been shown to be an effective analgesic for children with extremity fractures, controversy exists as to whether its use may be detrimental to fracture healing. This is problematic as common alternatives, specifically acetaminophen and opiates, can be ineffective or have troublesome side effects. This study aims to shed light on the possible association between NSAIDs and fracture complications in pediatric patients.
To determine if exposure to ibuprofen is associated with an increased risk of bone healing complications in children with fractures.
Children between the ages of 6 months and 17 years of age who experienced a fracture of the tibia, femur, humerus, scaphoid, or 5th metatarsal presenting to an academic pediatric emergency department between January 2003 and October 2014. These fractures were chosen due to literature associating them with a higher risk of bone healing complications.
Exposure to ibuprofen in the pediatric emergency department, during hospitalization or if the was prescribed ibuprofen upon discharge.
Patients without known NSAID exposure during hospitalization or discharge.
Primary: The presence of a bone healing complication as evidenced by nonunion, delayed union, or re-displacement on follow-up radiographs, as determined by an attending pediatric radiologist.
Single center retrospective cohort study. Multivariable logistic regression was employed to adjust for a number of potential confounders
Patients initially cared for at an outside hospital.
Patients who did not follow up with the orthopedic service.
Patents who had a medical history placing them at increased risk for a bone healing complication (e.g., a history of osteogenesis imperfecta, osteomyelitis, neoplasm, diabetes, nutritional deficiencies requiring replacement therapy, or were exposed to corticosteroids or chemotherapy in the 3 months prior to sustaining the fracture).
Patients who had an open or pathologic fracture.
Patients who had a prior fracture at the same site.
- 1,192 Records were found to be eligible for the study
- 808 patients included in the final analysis
- 384 (32%) patients were excluded based on the exclusion criteria listed above
- 298/384 (77%) were excluded for being lost to follow-up
- 27/808 (3%) patients were found to have complications
- 10/27 (37%) complications were in patients exposed to ibuprofen
- 17/27 (63%) complications were in patients not known to be exposed to ibuprofen
- No statistical association between NSAIDs and complications even when adjusted for known covariates
- Scaphoid fractures were found to have a statistically higher complication rate when compared to the other fractures
- Addresses an important issue (safe analgesia in pediatric patients with fractures) with minimal existing research
- Studied fractures at increased risk for healing complications
- Single center retrospective study
- Retrospective nature does not allow for analysis of true exposure to NSAIDs. Patients in “non-exposure” group may have taken NSAIDs as outpatient and patients prescribed NSAIDs may never have taken them
- Intention to treat was used and outpatient compliance of NSAID use, with or without a prescription could not be confirmed
- The authors do not discuss how consistent data extraction is. There’s no discussion of agreement on data extraction.
- Complications defined by historical radiology reads per chart by multiple radiologists. Definitions and sensitivity may vary among these radiologists
- Possible confounding variables missed or excluded
“Children with extremity fractures who are exposed to ibuprofen do not seem to be at increased risk for clinically important bone healing complications.”
NSAIDs are a staple in the treatment of pediatric pain, irritation and inflammation due to their safety profile and tolerability. Although randomized controlled animal studies demonstrate an association between NSAID administration and bone healing complications, data from human studies are inconsistent in their conclusion. This study strengthens the argument that NSAIDs can be safely used in the treatment of pain associated with extremity, even those with high complication rates. However, a multi-center randomized controlled study is required to properly address this question.
Potential Impact To Current Practice
The level of evidence of this data is inadequate to recommend any change in practice.
Although NSAIDs may be safe, there is currently inadequate evidence to recommend for or against their use in pediatric patients with fractures. The theoretical risk of impaired fracture healing must be evaluated against the potential harms of alternate treatment approaches (i.e. side effects of opiates) when determining the best course of action.
The Short Coat: A Disunion of the Literature: NSAIDS and Fracture
Dodwell ER et al. NSAID exposure and risk of nonunion: a meta-analysis of case-control and cohort studies. Calcif Tissue Int 2010; 87(3): 193-202. PMID: 20552333
Kay RM et al. Complications of ketorlac use in children undergoing operative fracture care. J Pediatric Orthop 2010; 30(7): 655-8. PMID: 20864848
Kurmis AP et al. The effect of nonsteroidal anti-inflammatory drug administration on acute phase fracture-healing: a review. J Bone Joint Surg Am 2012; 94((): 815-23. PMID: 22552671