Response: Abnormal ALP Isoenzyme in Children with Epilepsy Treated with Carbamazepine

Abstract

To the Editor: We read with great interest the letter of Okazaki et al. about the abnormal alkaline phosphatase (ALP) isoenzyme in children with epilepsy treated with carbamazepine (CBZ). This drug is actually one of the most frequently prescribed antiepileptic drugs (AEDs); despite a large clinical application, however, the precise mechanism(s) of action of CBZ remains poorly understood as does the pathophysiology of its side effects. A deceleration of skeletal growth and diminished bone mineral density was occasionally reported in some patients treated with CBZ (1,2), but the exact mechanisms of this adverse effect are still unknown. Recently it was demonstrated that CBZ increases ALP activity in the serum of epilepsy patients (3–5); moreover, some researchers found a positive relation between the serum ALP and the serum level of CBZ (6); more recently, O'Hare et al. (7) demonstrated that ALP elevation in patients receiving CBZ had a positive relation with both the duration of treatment and the drug dose. At least six different ALP isoforms exist: one bone/intestinal, two bone, and three liver isoforms; in most of these studies, the fraction of ALP found increased in CBZ-treated patients was the bone isoenzyme, suggesting the presence of an accelerated bone-turnover rate, which is possibly owing to an increased microsomal liver P450 oxidase activity resulting in increased conversion of vitamin D to inactive metabolites and that these epilepsy patients are at greater risk of development of rickets (8). Therefore the report of the three children with epilepsy encountered by Okazaki et al. is of special interest: they found an anomalous ALP isoenzyme band similar to that detected in benign transient hyperphosphatasemia. Although the clinical significance of this anomalous ALP isoenzyme is not clear, if the increase of anomalous ALP isoenzyme is found in other patients, another possible mechanism of the ALP increase due to CBZ action could be supposed.