Purpose: There is a strong scientific rationale to support the view that cytochrome P450 (CYP P450) enzyme-inducing AEDs induce bone loss in patients with epilepsy. However, no study has investigated the association between CYP 2C9 polymorphism and bone mineral density (BMD), 25-hydroxyvitamin D or parathyroid hormone levels in patients with epilepsy. This study sought to determine the association between BMD and CYP 2C9 polymorphism.
Methods: Ninety-three patients taking phenytoin as monotherapy were examined for CYP 2C9 polymorphism, vitamin D level and parathyroid hormone level and underwent basic chemistry testing. The bone mineral density of the lumbar spine and left femur were measured using dual-energy X-ray absorptiometry.
Results: The results indicated that about 18.3% of the patients with epilepsy were positive for CYP2C9*3. Furthermore, bone mineral density was associated with CYP 2C9 polymorphism epileptic patients. Specifically, patients with 2C9 polymorphism had higher T-scores and Z-scores of the femoral neck (p=0.02 and 0.04, respectively), but not of the lumbar spine (p=0.27 and 0.06, respectively). There was also a trend of having higher serum PTH levels and statistically significantly lower 25-hydroxyvitamin D levels in patients with wild type than in those compared with CYP 2C9 polymorphism (p=0.05 and 0.03, respectively). Additionally, the patients with CYP 2C9 polymorphism had higher plasma levels of phenytoin, particularly when compared with those with wild type (p=0.01). However, there was no association between serum levels of phenytoin and low BMD at femoral neck or lumbar spine.
Conclusion: CYP 2C9 polymorphism is associated with higher BMD, independent of plasma levels of phenytoin.
Keywords: Bone health; CYP 2C9 polymorphism; Phenytoin; Thailand.
Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.