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

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.

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.

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.

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.