Antiepileptics and bone health

Ther Adv Musculoskelet Dis. 2011 Oct;3(5):235-43. doi: 10.1177/1759720X11410769.


In recent years there has been increasing evidence suggesting that epilepsy and its treatment can have adverse effects on bone mineralization and calcium metabolism. Many studies have shown a significant reduction in bone mineral density (BMD) and an increased fracture risk in patients treated with enzyme-inducing antiepileptics (phenobarbital, carbamazepine, phenytoin). It is assumed that CYP450-inducing antiepileptic drugs (AEDs) upregulate the enzymes which are responsible for vitamin D metabolism, with the effect of converting 25(OH) vitamin D into inactive metabolites, resulting in reduced calcium absorption with consecutive secondary hyperparathyroidism. Data on bone-specific effects of newer AEDs are limited; nevertheless, alterations of bone metabolism have been reported for oxcarbazepine, gabapentin and, in preclinical studies, for levetiracetam. Prophylactic administration of adequate amounts of calcium and vitamin D is recommended for all patients. For patients with long-term AED exposure, BMD measurement is recommended as part of osteoporosis investigation (especially for patients treated with enzyme-inducing AEDs and where there are major risk factors for fractures). Drug therapy (bisphosphonates) is reserved for the treatment of patients who have a high fracture risk; there are no specific intervention studies available in patients with epilepsy.

Keywords: antiepileptics; epilepsy; fracture; metabolic bone disease; osteoporosis.