Adverse effects of antiepileptic drugs on bone mineral density in children

Abstract

Bone mineral content (BMC) or density (BMD) may be decreased in children with epilepsy either as a consequence of the epilepsy, the condition that caused the epilepsy or the treatment for epilepsy. This paper investigates the effects of antiepileptic drugs (AEDs) on BMD in children. A systematic search of Pubmed resulted in 14 papers that described changes in BMD in children on AEDs. For phenytoin, one study failed to show a decrease in femur BMD, whereas another study reported a decrease in total body and spine BMD, but only with the use of phenytoin for > 2 years. With phenytoin combined with a ketogenic diet, a decrease in forearm BMC was seen. For phenobarbital, one study showed a decrease in spine and total body BMD, but only among those who had used phenobarbital for > 2 years. Six studies were available for carbamazepine, and none of these showed a decrease in BMD in any skeletal site. For valproate, results were diverse; two studies reported a decrease in spine BMD, whereas two other studies did not. Two studies reported a decrease in hip BMD with valproate, whereas one did not. All three studies on forearm BMD in users of valproate described a decrease. Three studies reported an improvement in BMC with vitamin D supplementation in children on AEDs. No reports on changes in BMD among users of newer AEDs are available. In conclusion, more evidence is needed for the effects on BMD in children, especially for newer AEDs. The available studies have all been cross-sectional, and longitudianal studies are needed along with studies on potential interventions in children with decreased BMD.

Effects of antiepileptic drug therapy on vitamin D status and biochemical markers of bone turnover in children with epilepsy

“…Observational studies have suggested that chronic treatment with AEDs altered the bone metabolism and might be a risk factor for suboptimal bone mineral density and osteopenia in children [23,55]. It has been hypothesised that there are direct and indirect mechanisms that could link AEDs with these effects.…”

“…This offers a pathophysiological explanation for why children treated with AEDs may have low BMD compared with healthy children. However, results from epidemiological studies supporting this biochemical hypothesis are still inconsistent [23,55]. Moreover, some studies reported abnormalities in the bone metabolism of patients treated with AEDs independently of vitamin D deficiency [3,67,68].…”

MANAGEMENT OF ENDOCRINE DISEASE: Diabetes and osteoporosis: cause for concern?

“…Final body height and body weight may thus be impaired when T1D debuts in childhood. Smaller bones may appear 'thinner' by DXA than larger bones because of the 2D scan technique applied by DXA (65), so patients with impaired growth may be deemed to have decreased BMD if they are not compared to subjects with similar body configurations. Patients with T2D, on the other hand, are often obese and thus have larger body frames than those of patients with T1D.…”

Long-term effects of a ketogenic diet on body composition and bone mineralization in GLUT-1 deficiency syndrome: A case series

“…More recently, studies in children with intractable epilepsy have consistently shown that a prolonged KD can induce a progressive loss of bone mineral content (BMC) associated with poor bone health status, probably as a consequence of a chronic acidic environment [15,16]. However, the long-term effects of a KD on bone mineral status of GLUT-1 DS patients are currently unknown.…”