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NSAIDs may increase stress fracture risk among soldiers
Active-duty U.S. Army soldiers are more likely to receive a diagnosis of stress fracture after receiving a prescription for an NSAID or acetaminophen when compared with soldiers who were not prescribed such pain relievers, with that risk further increasing during the basic combat training period, according to findings published in the Journal of Bone and Mineral Research.
The use of NSAIDs, such as ibuprofen and naproxen, is widespread, with 12% of U.S. adults reporting taking NSAIDs at least 3 days per week for more than 3 months and more than 80% of U.S. soldiers filling at least one NSAID prescription annually, Julie M. Hughes, PhD, a research physiologist with the military performance division of the U.S. Army Research Institute of Environmental Medicine, and colleagues wrote in the study background. Impaired fracture healing with NSAID use has been documented, the researchers noted, and has been partially attributed to antiprostaglandin activity of NSAIDs.
“Suppression of the adaptive bone formation response with NSAID use has been experimentally demonstrated in animals and provides biological plausibility for increased stress fracture risk,” the researchers wrote. “Nevertheless, the relationship between NSAID use and stress fracture risk in humans is unknown.”
In a nested, case-control study, Hughes and colleagues analyzed data from U.S. Army soldiers enlisted or commissioned between 2002 and 2011, using data from the Total Army Injury and Health Outcomes Database, identifying incident stress fracture diagnoses via ICD-9 codes (n = 24,146). Researchers used risk-set matching to pair each stress fracture case with four controls on the date of an identified case’s injury, matched by length of time in service (n = 96,584). Researchers defined patients as NSAID users if they were prescribed an NSAID 30 to 180 days before the date of a confirmed stress fracture diagnosis or before the date of matching for controls, and additionally identified soldiers who participated in basic combat training, a 10-week period of heightened physical activity at the onset of Army service. Researchers used conditional logistic regression to calculate incident rate ratios for the association between NSAID prescriptions and stress fracture diagnosis.
The researchers found that NSAID prescription was associated with a 2.9-fold increase in stress fracture diagnoses (RR = 2.9; 95% CI, 2.8-2.9), whereas acetaminophen was associated with a 2.1-fold increase (RR = 2.1; 95% CI, 2-2.2).
During basic combat training, researchers found that the RRs increased to 5.3 for soldiers prescribed NSAIDs (95% CI, 4.9-5.7) and 4.4 for soldiers prescribed acetaminophen (95% CI, 3.9-4.9). Results persisted after adjustments for sex, age, race, education level and BMI.
“Given the widespread use of NSAIDs in the general and athletic populations, and given our findings suggesting an elevated risk of stress fracture during the physically demanding period of [basic combat training], prospective, observational studies and randomized controlled trials should be performed to confirm whether there is an elevated risk of stress fracture in physically active populations who commonly use these drugs,” the researchers wrote. – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.