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Risk of Fractures and Other Injuries in Children Treated with Antiseizure Medications for Epilepsy

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Abstract

This study aimed to investigate the prevalence of fractures and non-fracture injuries, including associated risk factors, in children with epilepsy prescribed antiseizure medications (ASM). A controlled, cross-sectional study was conducted in a hospital outpatient setting, comparing children with epilepsy prescribed ASMs with their non-epileptic siblings. Information was collected by questionnaire included history of fractures, non-fracture injuries and epilepsy, comorbidities and ASM use. 261 participants completed the questionnaire, 133 children with epilepsy (aged 10.7 ± 3.5 years, mean ± SD) and 128 siblings (10.1 ± 3.7 years). There were 49 non-seizure-related fractures in 34 ASM patients while prescribed ASMs, compared with 21 lifetime fractures in 15 controls, giving a 2.7 (95% CI 1.3–5.3, p = 0.007) times greater fracture prevalence in children treated with ASMs compared to healthy siblings. The rates of non-fracture injuries were similar across groups, except that concussion was more common in children taking ASMs (9.0% vs 1.6%, p = 0.026). Duration of ASM use and generalized tonic–clonic seizures (GTCS) were independent predictors of fractures (OR 1.55; 95% CI 1.03–2.31, p = 0.03; OR 2.50; 95% CI 1.05–5.94, p = 0.04, respectively). Fewer than 20% of participants and/or their families were aware that ASM use was related to bone health. Children with epilepsy treated with ASMs had a higher fracture prevalence than their sibling controls. Duration of ASM treatment and GTCS were associated with fracture risk. Longitudinal prospective studies are required to further explore risk and the direct impact of epilepsy on bone health.

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Acknowledgements

The authors thank the following for participation and assistance in this study: participants and their families; neurologists and other staff at the Royal Children’s Hospital Melbourne (RCH) epilepsy clinics.

Funding

No funding including honorariums or grants were obtained for the use of this research or manuscript production. The authors have full control of all primary data and agree to allow Calcified Tissue International to review the data if requested.

Author information

Authors and Affiliations

  1. Faculty of Medicine, Dentistry, and Health Sciences, University of Melbourne, Melbourne, VIC, Australia

    Sunita M. Kumar & Manikkuwadura De Silva l

  2. Department of Endocrinology and Diabetes, Royal Children’s Hospital, 50 Flemington Road, Parkville, VIC, 3052, Australia

    Peter J. Simm

  3. Murdoch Children’s Research Institute, Melbourne, Australia

    Peter J. Simm

  4. Department of Pediatrics, University of Melbourne, Melbourne, VIC, Australia

    Peter J. Simm

  5. Monash Department of Epidemiology, Cabrini Institute, Cabrini Health, Malvern, Australia

    Alexandra Gorelik

  6. Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Australia

    Alexandra Gorelik

  7. Department of Medicine (RMH), University of Melbourne, Melbourne, VIC, Australia

    Alexandra Gorelik, Baemisla Shiek Ahmad & John D. Wark

  8. Department of Neurology and Murdoch Children’s Research Institute, The Royal Children’s Hospital, Melbourne, VIC, Australia

    Jeremy L. Freeman & Mark T. Mackay

  9. Center for Biomedical Research Transparency, New York, NY, USA

    Sandra J. Petty

  10. CCS, Monash University, Melbourne, Australia

    Sandra J. Petty

  11. Department of Neurology, Alfred Health, Melbourne, Australia

    Sandra J. Petty

  12. Department of Neuroscience, St. Vincent’s Hospital, Melbourne, VIC, Australia

    Sandra J. Petty

  13. Bone and Mineral Medicine, Royal Melbourne Hospital, Melbourne, VIC, Australia

    John D. Wark

  14. Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Melbourne, Australia

    John D. Wark

Authors
  1. Sunita M. Kumar
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  2. Peter J. Simm
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  3. Manikkuwadura De Silva l
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  4. Alexandra Gorelik
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  5. Jeremy L. Freeman
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  6. Mark T. Mackay
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  7. Baemisla Shiek Ahmad
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  8. Sandra J. Petty
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  9. John D. Wark
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Corresponding author

Correspondence to Peter J. Simm.

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Conflict of interest

J.L. Freeman reports having received consulting fees from Eisai Australia, Liva Nova Australia and from UCB Australia. J.D. Wark has received grants-in-aid for unrelated projects in epilepsy treatment by UCB Pharma and Novartis. S.M. Kumar, P.J. Simm, M. De Silva, A. Gorelik, M.T. Mackay, B. Shiek Ahmad and S.J. Petty reports no disclosures.

Ethical Approval

The study was approved by the Royal Children’s Hospital Human Research Ethics Committee (HREC35100A).

Consent to Participate

Written informed consent was obtained from participants over the age of 18 years and from parents or guardians of participants under the age of 18 years.

Consent for Publication

All authors have consented to the submitted manuscripts publication.

Human and animal rights

Human rights were followed as the study was conducted under the approval of our HREC. Animal rights were not relevant as this is a study in humans.

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Cite this article

Kumar, S.M., Simm, P.J., De Silva l, M. et al. Risk of Fractures and Other Injuries in Children Treated with Antiseizure Medications for Epilepsy. Calcif Tissue Int 109, 139–146 (2021). https://doi.org/10.1007/s00223-021-00842-3

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  • DOI: https://doi.org/10.1007/s00223-021-00842-3

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