Treatment with methylphenidate and the risk of fractures among children and young people: A systematic review and self-controlled case series study

Aims: Animal studies suggest that methylphenidate treatment for around 3 months may lead to less mineralized and weaker appendicular bones. A systematic review was conducted to summarize the evidence from observational studies, and a self-controlled case series study was used to compare the risk before and after treatment initiation. Methods: Literature search was conducted using PubMed, Embase and the Cochrane Library to identify observational studies on methylphenidate and fractures. We also conducted a self-controlled case series study with individuals aged 5–24 years who received methylphenidate treatment and experienced fractures from 2001 to 2020 in Hong Kong. Incidence rate ratios and 95% confidence intervals were calculated by comparing the incidence rate in the methylphenidate-exposed period compared with nonexposed period. Results: Six cohort studies and 2 case–control studies were included in the systematic review. For all-cause fractures, studies found a 39–74% lower risk in treated-attention deficit hyperactivity disorder (ADHD) group compared with untreated ADHD but no difference between stimulants and nonstimulants. Differences between sexes and treatment duration were also found—significant results were shown in males and those with longer treatment duration. Among 43 841 individuals with ADHD medication before the year 2020, 2023 were included in the self-controlled case series analysis. The risks of fractures were lower by 32–41% in different treatment periods when compared with 6 months before treatment initiation. Conclusion: Methylphenidate treatment may lower the risk of all-cause fractures from both study designs; however, further evidence is needed about the treatment duration and sex effect. Conclusions on stress fractures are not yet established, and further research is required.