Adverse effects of valproate on bone: Defining a model to investigate the pathophysiology

SM Senn; S Kantor; IJ Poulton; MJ Morris; NA Sims; TJ O'Brien; JD Wark

Journal article

Adverse effects of valproate on bone: Defining a model to investigate the pathophysiology

SM Senn, S Kantor, IJ Poulton, MJ Morris, NA Sims, TJ O'Brien, JD Wark

Epilepsia | Published : 2010

DOI: 10.1111/j.1528-1167.2009.02516.x

Abstract

Purpose: Bone disease and fractures are common with chronic antiepileptic drug (AED) therapy, but the underlying mechanisms are poorly understood. This study aimed to characterize adverse bone effects of valproate and to identify mouse strains either resistant or sensitive to these effects. Methods: Seven mouse strains (n = 40/strain; 10/diet) were screened for the effect of chronic (8 weeks) valproate treatment (0, 2, 4, and 6 g/kg food) on total bone mineral content (BMC, by dual energy x-ray absorptiometry). In a confirmatory study the effect of valproate (0 or 4 g/kg food) over 16 weeks was assessed in five of the mouse strains (n = 60/strain; 30/diet) identified in the screening phase a..

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University of Melbourne Researchers

Natalie Sims Author

John Wark Author

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Grants

Awarded by NHMRC

Funding Acknowledgements

The authors would like to acknowledge Dr Sofianos Andrikopoulos for his contribution to the evolution of these studies. Sanofi-Aventis (Australia) provided an unrestricted grant that partially funded the first part of this study (Study A). The study was also partially funded by an NHMRC project grant (#400089) to John Wark and Terence O'Brien.