Background: Previous research has detected an increased risk of stress fractures among subjects who reported previous use of methylphenidate. Conversely, stimulant medication use has been associated with traumatic fracture risk reduction, possibly because of the improved control of the underlying symptoms of attention deficit hyperactivity disorder (ADHD). The goal of this study was to investigate the effect of previous methylphenidate use on the incidence of traumatic and stress fractures among combat soldiers with previously treated and untreated ADHD. Methods: The retrospective cohort included 100,000 combat soldiers recruited to the Israeli Defense Forces from 2005 through 2015. Diagnosis of ADHD and previous exposure to methylphenidate were determined on the basis of self-reported recruitment questionnaires and medical records. Accordingly, the cohort was divided into 3 groups: subjects with ADHD who were previously treated with methylphenidate (n = 689), untreated subjects with ADHD reporting no medication use (n = 762), and controls having no ADHD diagnosis (n = 98,549). Logistic regressions were fitted to determine the odds ratios (ORs) of study subjects for stress and non-stress (traumatic) fractures. Multivariate analysis incorporated baseline characteristics, including age, sex, weight, duration of service, and diagnosis of anemia, at some point during the service. Results: After adjustment for sex, anemia, weight, age, and duration of service, the risk of traumatic fractures was increased in both subjects with treated ADHD (OR, 1.03 [95% confidence interval (CI), 1.00 to 1.05]) and subjects with untreated ADHD (OR, 1.04 [95% CI, 1.02 to 1.07]) compared with controls. Subjects in the treated ADHD group were at a higher risk of stress fractures (OR, 1.04 [95% CI, 1.02 to 1.07]). Interestingly, a diagnosis of anemia was an independent predictor of stress fractures (OR, 1.05 [95% CI, 1.04 to 1.06]). Conclusions: Methylphenidate use is associated with an increased risk of stress fractures but a decreased risk of traumatic fractures in individuals diagnosed with ADHD. These and previous findings may serve as sufficient basis for screening for other risk factors and perhaps taking prevention measures in all those using stimulant medications, especially those planning to engage in strenuous physical activity. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
This study supports the hypothesis that an MP-associated reduction in BMD has a clinical effect in the form of an increased incidence of stress fractures. The high percentage of fractures attributed to MP use may serve as a basis for risk stratification, that is, the referral of patients with a history of MP use to BMD measurements.
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