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Fractures, decreased bone strength highly likely among children on AEDs

06 Oct 2017

Young people treated with antiepileptic drugs (AEDs) are at increased risk of fracture, with a recent study showing that such individuals exhibit reduced trabecular bone mineral density that correlates with clinically observed fractures.

Researchers performed a case–control study using an AED exposure–discordant matched-pair approach. They recruited a total of 23 pairs aged 5 to 18 years, including seven twins, 14 nontwin siblings and two cousin pairs. The median age was 12.9 years in cases and 13.5 years in controls.

Assessments were performed using dual energy x-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT) and muscle force/balance test. Questionnaires were also administered for data on bone health and epilepsy.

The prevalence of fractures was particularly greater in the group taking AEDs vs controls (15 fractures in eight cases vs four fractures in three controls; p<0.01).

Results from pQCT showed the trabecular volumetric bone mineral density (vBMD) at the tibia was lower by 14 percent in AED users vs controls (p=0.03). Furthermore, AED users exhibited decreased maximum force relative to body weight (Fmax total/g) at the tibia. No differences were observed in either bone mineral parameters measured by DXA or balance measures.

The current data demonstrate that children prescribed AEDs have an increased occurrence of fracture, decreased bone strength and lower limb muscle function, researchers said, while highlighting the need to validate the results in a larger, longitudinal study investigating the relationship between AED exposure and adverse outcomes in the developing skeleton over time.

It is possible that AEDs have a direct effect on reducing bone formation, researchers noted. A previous animal study has demonstrated a direct effect of carbamazepine and phenytoin on voltage-gated sodium channels within osteoblasts, which may explain the observed decline in bone density in the current study. [Epilepsia 2016;57:1398–1405]

AED-independent mechanisms related specifically to the epilepsy state are also likely, with recent evidence reporting reduced bone mass accrual in the absence of AED use. [Exp Neurol 2017;291:98–105]

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