Incidence of Fractures among Epilepsy Patients: A Population-based Retrospective Cohort Study in the General Practice Research Database


Address correspondence and reprint requests to Dr. P.C. Souverein at Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, P.O. Box 80082, 3508 TB Utrecht, The Netherlands. E-mail:


Summary: Purpose: To compare the incidence of various fractures in a cohort of patients with epilepsy with a reference cohort of patients not having epilepsy.

Methods: Patients were included in the epilepsy cohort if they had at least one diagnosis of epilepsy in their medical history and had sufficient evidence of “active” epilepsy (use of antiepileptic drugs, diagnoses) after the practice was included in the General Practice Research Database (GPRD). Two reference patients were sampled for each patient with epilepsy from the same practice. Primary outcome was the occurrence of any fracture during follow-up. Poisson regression analysis was used to estimate incidence density ratios (IDRs).

Results: The study population comprised 40,485 and 80,970 patients in the epilepsy and reference cohorts, respectively. The median duration of follow-up was ∼3 years. The overall incidence rate in the epilepsy cohort was 241.9 per 10,000 person-years. This rate was about twice as high as that in reference cohort: age- and sex-adjusted IDR, 1.89 (95% CI, 1.81–1.98). When comparing IDRs among the different groups of fractures, the highest relative-risk estimate was found for hip and femur fractures (adjusted IDR, 2.79; 95% CI, 2.41–3.24). IDRs were consistently elevated across age and sex groups and across fracture subtypes.

Conclusions: The overall risk of fractures was nearly twice as high among patients with epilepsy compared with the general population. The relative fracture risk was highest for hip and femur. Further study is necessary to elucidate whether this elevated risk is due to the disease, the use of antiepileptic drugs, or both.