Clin Osteol 2012; 17(3): 90-97

Antiepileptics - pathogenetic mechanism of the effect on bone metabolism and requirements for monitoring antiepileptic drug-induced bone conditionsReview articles

Franeková L., Zárubová J., Rovenský J.

Apart from epilepsy, antiepileptic drugs have been used to treat migraine, bipolar disorder and chronic pain. Long-term use of antie­ pileptics is associated with bone conditions such as osteopenia, osteoporosis and osteomalacia. The laboratory findings include nor­ mal or decreased calcium concentration, increased levels of bone remodeling markers, normal or decreased vitamin D concentrations and normal or increased parathormone levels. The most severe forms of bone disease are observed in antiepileptics inducing cyto­ chrome P450 (phenytoin, carbamazepine, phenobarbital, primidone, topiramate > 200 mg/day) and valproate known to be associated with growth disorders if used in childhood. So far, few studies have been published on the effect of newer antiepileptics on the skele­ ton. From that perspective, lamotrigine seems to be safe. The article provides a detailed description of the mechanism of interference of cytochrome P450 inducers with vitamin D metabolism, accelerating its conversion into inactive metabolites, as well as of other me­ chanisms of the adverse effects these drugs have on bone metabolism - decreased intestinal absorption of calcium independent of vi­ tamin D, hyperparathyroidism, direct osteoclast stimulation, vitamin K deficiency, drug-induced hypogonadism, decreased calcitonin secretion and hyperhomocysteinemia. Also mentioned are views of the potential mechanism of valproate effects on the skeleton, es­ pecially through changes in hormone levels. Topiramate and zonisamide are antiepileptics inhibiting carbon ting patients at risk of metabolic acidosis, hypercalciuria with urinary stone formation and osteoporosis. It is stil important. Requirements for monitoring the adverse effects of antiepileptic on the skeleton are particularly important in patients with long-term cytochrome P450 inducer and valproate therapy. These patients should have adequate intake of calcium and vitamin D. Their calci­ um, phosphorus and vitamin levels should be monitored. At least once every 5 years, they should undergo bone densitometry. Patients with other risk factors for osteoporosis (in particular postmenopausal females and males aged 65 or more) quently

Keywords: antiepileptics, osteoporosis, osteomalacia, cytochrome P450 inducers, bone mineral density (BMD)

Published: December 11, 2012  Show citation