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

INTRODUCTION: 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 from 5-24 years who received methylphenidate treatment and experienced fractures from 2001-2020 in Hong Kong. Incidence rate ratios and 95% confidence intervals were calculated by comparing the incidence rate in the methylphenidate-exposed period compared to non-exposed period.

RESULTS: Six cohort studies and two case-control studies were included. For all-cause fractures, studies found a 39-74% lower risk in treated-ADHD group compared with untreated-ADHD, but no difference between stimulants and non-stimulants. 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 year 2020, 2,203 were included in the self-controlled case series analysis. The risks of fractures were lower by 32-41% in the different treatment periods when compared with 6-month before treatment initiation.

CONCLUSION: In 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.