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Anti-epileptic drugs and bone loss: phenytoin reduces pro-collagen I and alters the electrophoretic mobility of osteonectin in cultured bone cells.
Wilson, Emma Garton, Mark Fuller, Heidi R.
Wilson, Emma
Garton, Mark
Fuller, Heidi R.
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Publication Date
2016-05-31
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Abstract
Phenytoin is an antiepileptic drug used in the management of partial and tonic-clonic seizures. In previous studies we have shown that valproate, another antiepileptic drug, reduced the amount of two key bone proteins, pro-collagen I and osteonectin (SPARC, BM-40), in both skin fibroblasts and cultured osteoblast-like cells. Here we show that phenytoin also reduces pro-collagen I production in osteoblast-like cells, but does not appear to cause a decrease in osteonectin message or protein production. Instead, a 24h exposure to a clinically relevant concentration of phenytoin resulted in a dose-dependent change in electrophoretic mobility of osteonectin, which was suggestive of a change in post-translational modification status. The perturbation of these important bone proteins could be one of the mechanisms to explain the bone loss that has been reported following long-term treatment with phenytoin.
Citation
Wilson, E. L., Garton, M., & Fuller, H. R. (2016). Anti-epileptic drugs and bone loss: Phenytoin reduces pro-collagen I and alters the electrophoretic mobility of osteonectin in cultured bone cells. Epilepsy Research, 122, 97-101. doi:http://dx.doi.org/10.1016/j.eplepsyres.2016.03.002
Publisher
Elsevier
Journal
Epilepsy Research
Research Unit
DOI
10.1016/j.eplepsyres.2016.03.002
PubMed ID
PubMed Central ID
Type
Article
Language
en
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Series/Report no.
ISSN
EISSN
1872-6844