AEDs Linked to Poor Bone Health in Kids

©Jarva Jar /Shutterstock.com

Young people who take antiepileptic drugs (AEDs) have more fractures, decreased trabecular bone mineral density, and less muscle force than children who don’t take AEDS, according to a study published inEpilepsia.

The study is the first to use a technique called peripheral quantitative computed tomography (pQCT) to evaluate BMD in children with epilepsy who are exposed to AEDs.

Past studies have found that children on AEDs have decreased BMD and increased fracture risk, but those studies used dual energy x-ray absorptiometry (DXA), which has limitations in growing children. DXA measures bone area, which may lead to inaccurate results due to variations in stature.  pQCT measures bone volume and can overcome these limitations. It can also measure trabecular bone, which can give an estimate of bone strength and fracture risk.

Researchers conducted a case-control study that included 23 pairs of children aged 5-18 years. Cases, or children with epilepsy treated with AEDs, were matched by age and sex to controls, or non-AED-exposed relatives (twins, non-twin siblings or first cousins). Cases were exposed to AEDs for at least 1 year, with a median exposure of 4 years.

Researchers evaluated BMD using DXA scanning of the right total hip, lumbar spine, and whole body, and trabecular volumetric bone mineral density (vBMD) using pQCT at the distal end of the tibia and the mid shaft of the tibia. They measured muscle force using the single two-legged jump test (assesses peak power) and multiple one-legged hop test (assesses peak force). They also assessed balance. Results were adjusted for bone age and development.

Key Results• Fracture prevalence: Increased in AED users vs nonusers (15 vs 4 fractures, respectively, p < 0.01)
• vBMD: Clinically significant 14% reduction in trabecular bone at the distal radius in AED users vs nonusers (p = 0.03)
• Muscle force: 17.5% decreased peak lower limb force in AED users vs nonusers (p<0.01)
• No statistically significant differences for DXA or balance measurements

The authors noted several limitations. While the matched case-control design allowed for partial control of genetic and environmental influences, it also limited the sample size. Such a small size may explain the nonsignificant DXA results for BMD, which was picked up by the more sensitive pQCT test.

They also pointed out that vitamin D status was not statistically different between AED users and nonusers. While some have hypothesized that impaired vitamin D synthesis related to AEDs may contribute to poor bone health, that does not explain the findings from this study. Instead, the study suggests AEDs may have a direct effect on bone and muscle independent of vitamin D metabolism.  However, to answer that question, further studies are needed. 

The authors concluded, “These results need to be validated in a larger, longitudinal study investigating the association between AED exposure and adverse outcomes in the developing skeleton over time.”

Take Home Points
• Small case-control study of children with epilepsy treated with AEDS matched to twins, siblings or cousins not on AEDs found increased prevalence of bone fractures in AED users
• AED users had reduced peak lower limb force and a clinically significant decrease in trabecular bone mineral density, a measure of bone strength, at the distal radius
• Vitamin D status was similar between AED users and nonusers, suggesting AEDs may have a direct impact on bone health
• Larger, longer duration studies are needed to confirm the results

References:

1. Simm PJ, Seah S, Gorelik A, et al. Impaired bone and muscle development in young people treated with antiepileptic drugs. Epilepsia. 2017 Nov;58:1931-1938.