The risk of bone fracture after long-term risperidone exposure is not increased compared to other atypical antipsychotics: A retrospective cohort study

Objective: Antipsychotic agents can increase circulating serum prolactin levels, potentially leading to osteoporosis and increased risk of bone fracture. The risk appears to be lower for atypical antipsychotics. We investigated whether risperidone was associated with an increased fracture risk by estimating the incidence of hip/femur and non-hip/femur fractures in users of risperidone, other atypical, and typical antipsychotics. Methods: This retrospective cohort study with a nested case-control study used claims data from the Taiwan National Healthcare Insurance database. All new users of antipsychotics between 2000–2012 were included. Incident fractures were identified using ICD-9 codes from inpatient records. Cox proportional hazards models compared fracture incidence among exposure groups. Conditional logistic regression models compared antipsychotic exposure among fracture cases versus matched controls. Results: 340,948 patients were included in the analysis. There were 2832 hip/femur fractures and 2693 non-hip/femur fractures: Hip/femur fracture incidence 636.8/100,000 person-years (Risperidone), 885.7/100,000 person-years (Other Atypical), 519.4/100,000 person-years (Typical). The adjusted hazard ratio of hip/femur fracture was 0.92 (95%CI 0.84–1.01) comparing Other Atypical with Risperidone, and 1.00 (95%CI 0.89–1.11) comparing Typical with Risperidone. The adjusted hazard ratio of non-hip/femur fracture was 1.08 (95%CI 0.98–1.20) for Other Atypical versus Risperidone, and 1.10 (95%CI 0.99–1.22) for Typical versus Risperidone. The adjusted odds ratio for hip/femur fractures was 0.92 (95% CI 0.83–1.01) in cases and controls exposed to other atypical antipsychotics compared with risperidone for 1 year prior to fracture date, 0.97 (95% CI 0.87–1.07) during 1–3 years, and 0.92 (95% CI 0.81–1.06) during 3–5 years prior to fracture date. The adjusted odds ratio for non-hip/femur fractures were 1.11 (95% CI 0.99–1.24), 1.02 (95% CI 0.0.91–1.14), and 0.95 (95% CI 0.82–1.09), respectively. Conclusion: There was no increased risk of bone fracture in long-term users of risperidone compared to users of other atypical antipsychotics.