Bone Abstracts (2015) 4 P128 | DOI: 10.1530/boneabs.4.P128

Patients treated with anti-epileptic drugs have a higher rate of fracture and impaired bone and muscle development compared with controls: results from a pilot study

Peter J Simm1,2, Sebastian Seah3, Mark Mackay2,4, Jeremy Freeman2,4, Sandra J Petty5,6 & John D Wark3,7


1Deparment of Endocrinology and Diabetes, Royal Children’s Hospital, Melbourne, Victoria, Australia; 2Murdoch Childrens Research Institute, Melbourne, Victoria, Australia; 3Deparment of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia; 4Deparment of Neurology, Royal Children’s Hospital, Melbourne, Victoria, Australia; 5Melbourne Brain Centre, Royal Melbourne Hospital, Melbourne, Victoria, Australia; 6Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia; 7Bone and Mineral Medicine, Royal Melbourne Hospital, Melbourne, Victoria, Australia.


Epilepsy is a relatively common condition of childhood, with anti-epileptic drugs (AEDs) the mainstay of medical therapy. AED use in adults has been shown to be associated with impaired bone density and increased risk of bone fracture. Paediatric data are more limited particularly in relation to fracture risk and skeletal geometry.

This study aimed to examine the within-pair differences in fracture prevalence and bone, muscle and balance parameters in sex-matched twin, sibling or first cousin pairs who were discordant for exposure to AED therapy, as a case-control, cross sectional study. Subjects were aged 5–18 years and had taken AEDs for at least 12 months. Members of each pair were aged-matched to within 2 years of each other. Questionnaires were used to obtain information about medical history, epilepsy history, bone health, and activity levels. Bone health was assessed using dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). For muscle force and balance parameters, the Leonardo ground force reaction platform (GFRP) was utilised. Serum 25-hydroxyvitamin D levels (25OHD) levels and bone age were also assessed.

A total of 23 matched pairs were recruited (seven twin, 14 sibling, and two cousin pairs). AED users showed an increased prevalence of fractures (n=15 vs 4 in control subjects), particularly at the distal radius. Concordantly, trabecular volumetric bone mineral density (vBMD) measured by pQCT at the 4% site of the tibia was reduced by 14% (P=0.02) in AED users. This was coupled with the finding that AED users exert a decreased maximum force (Fmax) on the tibia as measured by Leonardo GFRP. There were no within-pair differences in bone mineral parameters measured by DXA; however, AED users showed a tendency towards decreased total and trabecular area at the 4% tibia and polar strength-strain index as revealed by pQCT. There was no balance impairment evident in the AED users in comparison to controls.

AED users therefore experienced more fractures and were found to have reductions in volumetric bone density and muscle force compared to their matched controls. These results suggest that those on AEDs have impairment in the muscle–bone unit and therefore have relative skeletal fragility. Future studies designed with a longitudinal approach are required to confirm these findings.

Disclosure: The authors declared no competing interests.

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