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Bone loss with antiepileptic drug therapy: a twin and sibling study

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Abstract

Summary

Changes in areal bone mineral density (aBMD) and other predictors of bone loss were evaluated in 48 same-sex twin/age-matched sibling pairs discordant for antiepileptic drug (AED) use. AED users had reduced BMD at the hip regions. Prolonged AED users had greater aBMD loss, predicting a higher risk of bone fragility.

Introduction

To investigate the longitudinal associations of bone mineral measures with antiepileptic drug (AED) use, including enzyme-inducing (EIAED) and non-enzyme-inducing (NEIAED) types, and other predictors of bone loss in a study of 48 same-sex twin/age-matched sibling pairs (40 female, 8 male) discordant for AED use.

Methods

Using dual-energy X-ray absorptiometry (DXA), areal bone mineral density (aBMD) and content (BMC) at the hip regions, forearm, lumbar spine, and whole body were measured twice, at least 2 years apart. The mean within-pair difference (MWPD), MWPD%, and mean annual rate of aBMD change were adjusted for age, weight, and height. Predictors of bone loss were evaluated.

Results

AED users, compared to non-users, at baseline and follow-up, respectively, had reduced aBMD at the total hip (MWPD% 3.8, 4.4%), femoral neck (4.7, 4.5%), and trochanter regions (4.1, 4.6%) (p < 0.05). For the whole cohort, the annual rate of change in all aBMD/BMC (p > 0.05) regions did not differ within pairs. Nevertheless, EIAED users had greater aBMD loss than non-users (n = 20 pairs) at the total hip (1.7 vs. 0.3%, p = 0.013) and whole body regions (0.7% loss vs. 0.1% BMD gain, p = 0.019), which was not found in NEIAED-discordant pairs (n = 16). AED use >20 years predicted higher aBMD loss at the forearm (p = 0.028), whole body (p = 0.010), and whole body BMC (p = 0.031).

Conclusions

AED users had reduced aBMD at the hip regions. Prolonged users and EIAED users had greater aBMD loss, predicting a higher risk of bone fragility. Further prospective studies of AED effects on bone microarchitecture are needed.

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Acknowledgments

The authors would like to express their highest appreciation to all participants for their invaluable contributions and commitments throughout the study, our collaborators, Ms. Mary Sakellarides who continued the work of Dr. Petty on baseline recruitment, the late Ms. Sue Kantor and Ms. Ashwini Kale at Bone and Mineral Medicine, the Royal Melbourne Hospital, for their assistance during the bone scanning of Melbourne-based participants, Professor Richard L Prince and his research team at the Sir Charles Gairdner Hospital for their support for study visits in Western Australia, Ms. Monique Macara from the RNSH who conducted the assessments for Sydney-based participants, the Australian Twin Registry, and all who have been involved with the University of Melbourne Twin and Sibling Research Program.

Author information

Authors and Affiliations

  1. Department of Medicine, The Royal Melbourne Hospital, University of Melbourne, Level 4, Clinical Sciences Building, Parkville, Victoria, 3050, Australia

    B. Shiek Ahmad, S. J. Petty, A. Gorelik, T. J. O’Brien, J. J. Christie & J. D. Wark

  2. Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia

    B. Shiek Ahmad

  3. Melbourne EpiCentre, The Royal Melbourne Hospital, Parkville, Victoria, 3050, Australia

    A. Gorelik

  4. School of Physiotherapy and Exercise Science, Curtin University, Perth, Western Australia, 6845, Australia

    K. D. Hill

  5. Department of Medicine, Royal North Shore Hospital, The University of Sydney, Sydney, New South Wales, 2006, Australia

    P. N. Sambrook

  6. The Royal Melbourne Hospital Bone and Mineral Service, Parkville, Victoria, 3050, Australia

    J. D. Wark

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  1. B. Shiek Ahmad
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  7. P. N. Sambrook
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Corresponding author

Correspondence to J. D. Wark.

Ethics declarations

The Melbourne Health Human Research Ethics Committee (HREC) (HREC 2003.249), Sir Charles Gairdner, HREC, Perth, and HARBOUR HREC of Northern Sydney Central Coast Health (NSCCH) (protocol 0409-199M (Q)) approved this multi-center study. All participants provided written informed consent. The project was approved by the Australian Twin Registry.

Disclosures

This research was funded by National Health and Medical Research Council project grant number (400089), by the Department of Medicine, University of Melbourne and by the Royal Melbourne Hospital Research Foundation. Professors Wark and O’Brien received research support from UCB Pharma and Novartis for unrelated studies. Dr. Petty received research support from UCB Pharma for an unrelated investigator-initiated study. Dr. Shiek Ahmad obtained financial support throughout her PhD from the University of Malaya and the Malaysian Ministry of Higher Education.

Conflicts of interest

None.

Declaration

The work described in this manuscript is consistent with the Journal’s guidelines for ethical publication. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Additional information

Professor Sambrook passed away in 2012

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Shiek Ahmad, B., Petty, S.J., Gorelik, A. et al. Bone loss with antiepileptic drug therapy: a twin and sibling study. Osteoporos Int 28, 2591–2600 (2017). https://doi.org/10.1007/s00198-017-4098-9

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  • DOI: https://doi.org/10.1007/s00198-017-4098-9

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