Anti-epileptic drugs associated with fractures in the elderly: a preliminary population-based study

Objective: Although classic anti-epileptic drugs have been associated with increased fracture risk, data are lacking on the outcomes of newer anti-epileptic drugs, such as gabapentin (GBP), levetiracetam, pregabalin, oxcarbazepine (OXC), and topiramate. This study was designed to determine fracture risks in the elderly associated with newly-developed anti-epileptic drugs.

Methods: A total of 2,169 patients (median age = 71.01 years, SD = 11.25 years) who experienced fractures between 2006 and 2013 were selected. For each case, age-, sex-, and comorbidity-matched controls were selected. The assessed clinical outcome was any fracture, and the use of anti-epileptic drugs was used as an exposure variable.

Results: There were no differences in age, sex, or comorbidities between patients and controls, but patients with fractures often lived in urban areas (odds ratio [OR] = 1.17; 95% confidence interval [CI] = 1.05–1.29) and had low income (OR = 1.14; 95% CI = 1.01–1.29) compared to controls. A significant increase in fractures was associated with OXC (OR = 3.31; 95% CI = 1.59–6.92), carbamazepine (CBZ; OR = 2.18; 95% CI = 1.31–3.61), and GBP (OR = 1.79; 95% CI = 1.01–3.18). Phenobarbital (OR = 1.97; 95%CI = 0.53–7.34), phenytoin (OR = 0.52; 95% CI = 0.23–1.16), levetiracetam (OR = 1.84; 95% CI = 0.55–6.16), valproic acid (OR = 1.01; 95% CI = 0.53–1.92), lamotrigine (OR = 1.44; 95% CI = 0.12–16.65), and topiramate (OR = 0.47; 95% CI = 0.10–2.31) were not associated with fracture risk.

Conclusions: CBZ, GBP, and OXC users have a significantly higher risk of fracture. Most recently-developed anti-epileptic drugs are not associated with an increased risk of fracture in individuals aged ≥50 years.