Association of antiepileptic drugs with nontraumatic fractures: a population-based analysis

Arch Neurol. 2011 Jan;68(1):107-12. doi: 10.1001/archneurol.2010.341.


Objective: To explore the relationship between antiepileptic drug (AED) use and nontraumatic fractures in those aged 50 years and older.

Design: Retrospective matched cohort study.

Participants: A total of 15,792 persons, identified through the Population Health Research Data Repository from Manitoba, Canada, with nontraumatic fractures of the wrist, hip, and vertebra occurring between 1996 and 2004. Each patient was matched for age, sex, ethnicity, and comorbidity with up to 3 controls (n = 47,289).

Interventions: Prior AED use (carbamazepine, clonazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, primidone, topiramate, valproic acid, and vigabatrin) was determined from pharmacy data in the repository. Odds ratios (OR) for fracture from AED exposure were adjusted for sociodemographic and comorbidity factors known to affect fracture risk.

Results: A significant increase in fracture risk was found for most of the AEDs being investigated (carbamazepine, clonazepam, gabapentin, phenobarbital, and phenytoin). The adjusted ORs ranged from 1.24 (95% confidence interval [CI], 1.05-1.47) for clonazepam to 1.91 (95% CI, 1.58-2.30) for phenytoin. The only AED not associated with increased fracture risk was valproic acid (adjusted OR, 1.10; 95% CI, 0.70-1.72).

Conclusions: Most AEDs were associated with an increased risk of nontraumatic fractures in individuals aged 50 years or older. Further studies are warranted to assess the risk of nontraumatic fractures with the newer AEDs and to determine the efficacy of osteoprotective medications in this population.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticonvulsants / adverse effects*
  • Cohort Studies
  • Databases, Factual
  • Female
  • Fractures, Bone / chemically induced*
  • Fractures, Bone / epidemiology*
  • Humans
  • Male
  • Middle Aged
  • Population Surveillance*
  • Retrospective Studies


  • Anticonvulsants