Anti-epileptic drugs and bone loss: phenytoin reduces pro-collagen I and alters the electrophoretic mobility of osteonectin in cultured bone cells.
AffiliationRJAH Orthopaedic Hospital; RJAH Orthopaedic NHS Foundation Trust; Keele University
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AbstractPhenytoin 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.
CitationWilson, 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
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