Effects of Antiepileptic Drugs on Bone Health and Growth Potential in Children with Epilepsy

Background Bone health may be impaired in children with epilepsy. Objectives Our objective was to characterize bone mineral density (BMD) and bone growth in children receiving antiepileptic drugs (AEDs) and to assess the effects of co-morbidity, vitamin D deficiency, and type of drugs used. Data sources Data were sourced from PubMed, Embase, and Web of Science. Eligibility criteria Cross-sectional, cohort, case-control, or randomized controlled trials reporting BMD or parameters of bone growth. Participants Children with epilepsy compared with controls. Interventions AEDS or ketogenic diet. Study appraisal The studies were evaluated by one author. Synthesis methods Studies were categorized as reporting reduced BMD or not at any skeletal site as outcome. A logistic regression was performed for age, percent boys, study design, type of AED, co-morbidity or not, and signs of vitamin D deficiency/osteomalacia or not. Results Carbamazepine and valproate were analyzed as monotherapy in 11 studies, and for both drugs a limited decrease in BMD seemed present. For oxcarbazepine, levetiracetam, phenytoin, phenobarbital, and topiramate, only one study with monotherapy was found for each drug, none of which reported decreased bone density. Polytherapy with AEDs seemed to be associated with a larger decrease in bone density than was monotherapy. Although few studies were available on bone growth, these did indicate that bone growth may be impaired among users of AEDs. Ketogenic diet may be associated with decreased bone density. The main determinant of normal BMD was absence of vitamin D deficiency/osteomalacia. Limitations The studies differed in skeletal sites studied and most were cross-sectional. No head-to-head comparisons of AEDs were performed. Children treated with polytherapy or ketogenic diet may have more complicated and severe disease than those treated with monotherapy. The underlying cause of epilepsy and vitamin D deficiency may contribute to impaired bone growth and density. Conclusions Reduced bone density, impaired bone growth, and vitamin D deficiency may be seen in children treated with drugs against epilepsy.