Vitamin D levels and bone turnover in epilepsy patients taking carbamazepine or oxcarbazepine

Epilepsia. 2006 Mar;47(3):510-5. doi: 10.1111/j.1528-1167.2006.00460.x.


Purpose: Evidence suggests that enzyme-inducing antiepileptic drugs (AEDs) may decrease serum 25-hydroxyvitamin D (25-OHD) levels and increase bone turnover. We sought to determine whether these are affected by treatment with carbamazepine (CBZ) or oxcarbazepine (OXC).

Methods: We measured serum levels of 25-OHD, parathyroid hormone (PTH), osteocalcin (OCLN), bone alkaline phosphatase (BAP), and urinary N-telopeptides of type I collagen cross-links (NTX) in normal controls (n=24) and in epilepsy patients taking CBZ (n=21) or OXC (n=24) in monotherapy. CBZ patients were subsequently switched overnight to OXC monotherapy, and after 6 weeks, the tests were repeated.

Results: 25-OHD levels were lower in each drug-treated group (OXC, 19.4+/-2.3 pg/ml; CBZ, 20.4+/-2.4) than in the controls (27.5+/-2.8) (ANOVA, p=0.052). This difference was significant for the OXC group (p<0.05). PTH, BAP, and NTX did not differ significantly among groups. OCLN levels were somewhat elevated in the OXC group (2.79+/-0.47 ng/ml) and more clearly and significantly elevated in the CBZ group (3.63+/-0.36) compared with controls (2.38+/- 0.41) (p=0.053). Because the data were very similar between OXC and CBZ groups, they were combined to increase statistical power. The combined drug-treatment group had significantly higher BAP (p=0.02) and lower 25-OHD (p=0.015) than did controls. The latter remained significant even after accounting for the confounding effects of age on 25-OHD levels (p<0.05). No significant differences were found after CBZ patients were switched to OXC.

Conclusions: Epilepsy patients taking OXC or CBZ have significantly lower 25-OHD than do normal controls, with a pattern of changes in other bone biomarkers suggestive of secondary hyperparathyroidism. It may be prudent for patients taking CBZ or OXC to be prescribed 25-OHD replacement.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alkaline Phosphatase / analysis
  • Alkaline Phosphatase / metabolism
  • Anticonvulsants / adverse effects
  • Anticonvulsants / pharmacokinetics*
  • Anticonvulsants / therapeutic use*
  • Biomarkers / metabolism
  • Bone Resorption / chemically induced
  • Bone Resorption / metabolism
  • Bone Resorption / prevention & control
  • Bone and Bones / drug effects
  • Bone and Bones / enzymology
  • Bone and Bones / metabolism*
  • Carbamazepine / adverse effects
  • Carbamazepine / analogs & derivatives*
  • Carbamazepine / pharmacokinetics*
  • Carbamazepine / therapeutic use*
  • Collagen / metabolism
  • Collagen / urine
  • Collagen Type I
  • Epilepsy / blood
  • Epilepsy / drug therapy*
  • Epilepsy / metabolism*
  • Female
  • Humans
  • Hyperparathyroidism, Secondary / chemically induced
  • Hyperparathyroidism, Secondary / metabolism
  • Hyperparathyroidism, Secondary / prevention & control
  • Male
  • Middle Aged
  • Osteocalcin / blood
  • Oxcarbazepine
  • Parathyroid Hormone / blood
  • Peptides / metabolism
  • Peptides / urine
  • Vitamin D / blood*
  • Vitamin D / metabolism*
  • Vitamin D / therapeutic use
  • Vitamin D Deficiency / chemically induced
  • Vitamin D Deficiency / metabolism
  • Vitamin D Deficiency / prevention & control


  • Anticonvulsants
  • Biomarkers
  • Collagen Type I
  • Parathyroid Hormone
  • Peptides
  • collagen type I trimeric cross-linked peptide
  • Osteocalcin
  • Vitamin D
  • Carbamazepine
  • Collagen
  • Alkaline Phosphatase
  • Oxcarbazepine