Past Methylphenidate Exposure and Stress Fractures in Combat Soldiers: A Case-Control Study

Introduction: Previous experimental and clinical research has revealed decreased bone mineral density among children and adolescents who receive methylphenidate (MP) treatment for ADHD. We decided to investigate the clinical impact of past MP use on the incidence of stress fractures (SF) in the military

Methods: Case-control study of combat soldiers: 2400 cases (at least one SF diagnosed by bone scan) and 6187 controls (no stress fractures throughout the service). Other variables included past use of MP, age, gender, place of birth, diagnosis of ADHD, and grade, side and location of each fracture. Measures of risk included odds ratios of SF, attributable proportion among the exposed (AP%) and population attributable fraction (PAF).

Results: Previous use of MP was associated with higher risk of SF (OR=1.814; 95%CI(1.282:2.586)). AP% was high (46.97%), PAF was about 1.08%. The risk of SF associated with past MP was preserved after adjustment for weight, gender and country of birth (p=0.005).

Conclusion: This study supports the hypothesis that MP-associated bone mineral density reduction has clinical impact in the form of increased incidence of SF. High etiologic fraction AP% may serve basis for risk stratification, i.e. referral of subjects with history of MP use to bone density measurement.