Vitamin D levels and bone turnover in epilepsy patients taking carbamazepine or oxcarbazepine.
OBJECTIVE
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.
Mintzer
Scott
S
Jefferson Comprehensive Epilepsy Center, Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. scott.mintzer@jefferson.edu
Boppana
Prashanthi
P
Toguri
Jeanne
J
DeSantis
Anthony
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000032:analysis / Q000378:metabolism; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D001862:Bone Resorption / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D001842:Bone and Bones / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002220:Carbamazepine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003094:Collagen / Q000378:metabolism / Q000652:urine; D024042:Collagen Type I; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D000078330:Oxcarbazepine; D010281:Parathyroid Hormone / Q000097:blood; D010455:Peptides / Q000378:metabolism / Q000652:urine; D014807:Vitamin D / Q000097:blood* / Q000378:metabolism* / Q000627:therapeutic use; D014808:Vitamin D Deficiency / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control
D000927:Anticonvulsants; D015415:Biomarkers; D024042:Collagen Type I; D010281:Parathyroid Hormone; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D014807:Vitamin D; D002220:Carbamazepine; D003094:Collagen; D000469:Alkaline Phosphatase; D000078330:Oxcarbazepine