The Role Of Reverse Causation In The Relationship Between NSAIDs And Stress Fractures In Army Trainees

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) suppress the bone anabolic response to exercise and may predispose individuals to stress fracture during heightened periods of physical activity. NSAIDs have been linked with increased risk of stress fracture during heightened periods of physical activity. These findings could potentially be attributed to reverse causation in which pain caused by undiagnosed stress fracture could result in increased prescriptions and use of NSAIDs. We evaluated whether the association between stress fracture risk and NSAID use persisted after accounting for reverse causation. METHODS: Self-reported NSAID use during U.S. Army Basic Combat Training (BCT) was collected weekly on a cohort of 2,482 (948 women, 1,534 men) trainees. Stress fractures were identified using International Classification of Diseases codes. The relationship between NSAID use and stress fracture was evaluated using multivariate logistic regression. To account for reverse causation, NSAIDs exposure was lagged weekly by excluding NSAID use 1 to 4 weeks before stress fracture diagnosis or study termination. All models were adjusted for sex, age, race/ethnicity, BMI, history of stress fracture, and pre-BCT sport participation. RESULTS: The study population was predominantly white (44%) with a mean ± SD age of 20.74 ± 3.71, and BMI of 20.74 ± 3.54. During BCT, 49 recruits were diagnosed with stress fractures, and 48 of those reported using NSAIDs at the time of diagnosis. The mean time to stress fracture diagnosis was 6.16 ± 2.12 weeks. The odds of stress fracture after 1 to 4 weeks of lagging NSAID use was 4.85 (95% CI: 2.26, 10.39), 4.74 (95% CI: 2.21, 10.15), 2.56 (95% CI: 1.25, 5.27) and 2.10 (95% CI: 1.03, 2.29), respectively. CONCLUSION: Stress fracture risk remained elevated after accounting for up to a 4-week lag in NSAID use, suggesting that reverse causation does not fully explain the association between NSAID use and stress fracture risk in Army trainees. Disclaimer: The views expressed in this abstract are those of the authors and do not reflect the official policy of the Department of Army, Department of Defense, or the U.S. Government.