Increased risk for stress fractures and delayed healing with NSAID receipt, U.S. Armed Forces, 2014-2018

Previous studies have suggested that the use of nonsteroidal antiinflammatory drugs (NSAIDs) is associated with an increased risk of stress fractures due to their inhibitory effect on bone formation. The current study evaluated the relative risk of stress fractures in active duty service members with and without previous receipt of NSAIDs. A total of 7,036 cases of stress fracture and 28,141 matched controls were identified between June 2014 and December 2018 and included in the analysis. A subset of cases were evaluated for delayed healing diagnoses within 90 days following incident case diagnosis using International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes. Prior receipt of NSAIDs was associated with an increased incidence of stress fractures (adjusted incidence rate ratio=1.70; 95% confidence interval [CI]:1.58-1.82; p<.0001). Among stress fracture cases, prior receipt of NSAIDs was associated with increased diagnosis of delayed healing (adjusted odds ratio=1.41; 95% CI: 1.12-1.77; p=.004). These findings may have significant implications for military readiness because NSAIDs are used extensively and stress fractures are already a major contributor to the burden of healthcare encounters and lost duty time.