Bone metabolism and vitamin D levels in carbamazepine-treated patients.

To the Editor: I read with great interest the paper by Mintzer et al. (1) about the vitaminDand bone turnover in epileptic patients receiving carbamazepine (CBZ) or oxcarbazepine (OXC) and found an increase in bone metabolism with low serum 25-hydroxyvitamin D (25-OHD). In our experience (2,3), patients treated by CBZ monotherapy showed a significant increase of bone turnover: in fact, we found higher values of markers of bone formation (serum bone alkaline phosphatase, osteocalcin, and propetides of types I and III procollagen) and of bone resorption (serum telopeptide of type I collagen and urineN-telopeptides of type I collagen) in patients than in controls. These data confirm the results of Mintzer et al. (1) who demonstrated significant increase in the bone formation markers. It is possible that these abnormalities were secondary to induction of hepatic microsomal enzymes. In contrast with the results of these authors (1), in our patients we did not find any significant changes in serum 25-OHD levels. There is a great debate about whether this increase in bone turnover is really due to decrease in 25-OHD. The absence of relationship between serum 25-OHD and serum concentration of CBZ shows that the increase of bone turnover can be independent of the effect of this antiepileptic drug on vitaminDmetabolism, as previously suggested (4,5). Moreover, very recently, also Pack et al. (6) found numerous abnormalities in bone turnover markers with 25-OHD normal levels in their CBZ treated patients. Although biochemical changes in the metabolism of vitamin D are observed during treatment with CBZ, whether clinically apparent and/or histological osteomalacia develops during treatment with the drug is still controversial; in fact, no difference in bone mineral density between patients and controls has been reported. Therefore, we do not agree with the suggestion of Mintzer et al. (1) who encourage 25-OHD replacement in patients receiving this drug, because this preventive treatment could not be always indicated.