The association between CYP 2C9 polymorphism and bone health

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.

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.

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.

CYP 2C9 polymorphism is associated with higher BMD, independent of plasma levels of phenytoin.