Effects of antiepileptic drug therapy on vitamin D status and biochemical markers of bone turnover in children with epilepsy

Abstract

Reports of decreased serum 25-hydroxyvitamin D (25-OHD) and altered bone metabolism associated with antiepileptic drug (AED) treatment are inconsistent and predominantly restricted to adults. In this cross-sectional observational study, the aim was to evaluate the influence of AED treatment on vitamin D status and markers of bone turnover in children with epilepsy. In 38 children taking AEDs and 44 healthy control subjects, blood samples were collected to determine the levels of serum 25-OHD, intact parathyroid hormone (iPTH), calcium (Ca), phosphate (P), bone alkaline phosphatase (BAP), osteocalcin (OC) and C terminal telopeptide of type I collagen (ICTP). More than 75% of the patients were vitamin D deficient (serum 25-OHD<20 ng/mL) and 21% of the patients had an insufficient vitamin D status (serum 25-OHD=20-30 ng/mL). In the patients, the serum levels of OC (p = 0.002) and BAP (p < 0.001) were significantly increased, but ICTP (p = 0.002) concentrations were significantly decreased compared with the control group. When patients where divided into two groups according to their medication (mono- or polytherapy), significantly lower 25-OHD (p = 0.038) and ICTP (p = 0.005) levels and elevated BAP (p = 0.023) concentrations were found in patients under polytherapy. An association between 25-OHD and the measured bone markers could not be determined. Our results indicate that the prevalence of vitamin D deficiency in epilepsy patients under AED treatment is high, especially under polytherapy, and alteration markers of bone formation and resorption suggests an accelerated skeletal turnover. The routine monitoring of serum 25-OHD and vitamin D supplementation on an individual basis should be considered.

Vitamin D levels in epileptic children on long-term anticonvulsant therapy

“…Several studies showed a reduction in 25(OH)D level in epileptic children who had used anticonvulsants for 6 months or more, 19,[28][29][30]32 while others did not. 17,34,36,38,39 These latter studies found this to be the case for non-enzyme-inducing anticonvulsants (valproic acid) use 36,38 or new anticonvulsants (lamotrigine, topiramate, oxcarbazepine, sulthiamine).…”

“…The subjects consumed valproic acid or carbamazepine as a monotherapy, or in combination with a new anticonvulsant. 29 A cohort study in Greece showed vitamin D deficiency in 49% of subjects. 30 However, that study used a lower definition of vitamin D deficiency (<10 ng/mL), therefore, higher prevalence of vitamin D deficiency was found if a higher definition of vitamin D deficiency (<20 ng/mL) was used, as we did in our study.…”

“…[21][22][23][24] Phenobarbital, phenytoin, carbamazepine, valproic acid, and oxcarbazepine were frequently studied for their impact on 25(OH)D levels. Most enzyme-inducing anticonvulsants (phenytoin, phenobarbital, primidone, and carbamazepine) were associated with low levels of vitamin D. 16,[25][26][27][28][29][30][31][32] Other studies showed insignificant effects, 24,[33][34][35] especially with valproic acid and newer anticonvulsants. 17,19,32,36 The prevalence of vitamin D deficiency has varied between 23 to 76%, depending on the definition of vitamin D deficiency, anticonvulsant type, number and duration of use, as well as the location of the study.…”

“…17,19,32,36 The prevalence of vitamin D deficiency has varied between 23 to 76%, depending on the definition of vitamin D deficiency, anticonvulsant type, number and duration of use, as well as the location of the study. 25,[27][28][29][30] Studies to assess for an association between anticonvulsants and vitamin D deficiency have had inconsistent results, especially for non-enzymeinducing anticonvulsants such as valproic acid. Therefore, further studies are still needed.…”

Seasonal variations in vitamin D levels in HIV-infected patients

“…It is not self-evident, though, that these results can be transferred to HIV-infected subjects: for patients on anticonvulsant drugs (which are considered to interfere similarly to ART [1]) and patients with hyperparathyroidism (which was found to occur secondary to ART with tenofovir disoproxil fumarate [5,6]) a loss of seasonality has been described [7,8]. Although a seasonal difference has been hinted at in some small or highly selective HIV-infected populations [9][10][11][12], detailed information is sparse.…”