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      Effects of Oxcarbazepine and Levetiracetam on Calcium, Ionized Calcium, and 25-OH Vitamin-D3 Levels in Patients with Epilepsy

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          Abstract

          Objective

          The primary objective of the present study was to further elucidate the effects of oxcarbazepine (OXC) and levetiracetam (LEV) monotherapies on the bone health status of patients with epilepsy.

          Methods

          This study included 48 patients who attended our epilepsy outpatient clinic, had a diagnosis of epilepsy, and were undergoing either OXC or LEV monotherapy and 42 healthy control subjects. The demographic and clinical features of the patients, including gender, age, onset of disease, daily drug dosage, and duration of disease, were noted. Additionally, the calcium, ionized calcium, and 25-OH vitamin-D3 levels of the participants were prospectively evaluated.

          Results

          The 25-OH vitamin-D3, calcium, and ionized calcium levels of the patients taking OXC were significantly lower than those of the control group. These levels did not significantly differ between the patients taking LEV and the control group, but there was a significant negative relationship between daily drug dose and ionized calcium levels in the LEV patients.

          Conclusion

          In the present study, anti-epileptic drugs altered the calcium, ionized calcium, and 25-OH vitamin-D3 levels of epilepsy patients and resulted in bone loss, abnormal mineralization, and fractures. These findings suggest that the calcium, ionized calcium, and 25-OH vitamin-D3 levels of patients with epilepsy should be regularly assessed.

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          Most cited references24

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          Descriptive Epidemiology of Epilepsy: Contributions of Population-Based Studies From Rochester, Minnesota

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            Incidence of fractures among epilepsy patients: a population-based retrospective cohort study in the General Practice Research Database.

            To compare the incidence of various fractures in a cohort of patients with epilepsy with a reference cohort of patients not having epilepsy. Patients were included in the epilepsy cohort if they had at least one diagnosis of epilepsy in their medical history and had sufficient evidence of "active" epilepsy (use of antiepileptic drugs, diagnoses) after the practice was included in the General Practice Research Database (GPRD). Two reference patients were sampled for each patient with epilepsy from the same practice. Primary outcome was the occurrence of any fracture during follow-up. Poisson regression analysis was used to estimate incidence density ratios (IDRs). The study population comprised 40,485 and 80,970 patients in the epilepsy and reference cohorts, respectively. The median duration of follow-up was approximately 3 years. The overall incidence rate in the epilepsy cohort was 241.9 per 10,000 person-years. This rate was about twice as high as that in reference cohort: age- and sex-adjusted IDR, 1.89 (95% CI, 1.81-1.98). When comparing IDRs among the different groups of fractures, the highest relative-risk estimate was found for hip and femur fractures (adjusted IDR, 2.79; 95% CI, 2.41-3.24). IDRs were consistently elevated across age and sex groups and across fracture subtypes. The overall risk of fractures was nearly twice as high among patients with epilepsy compared with the general population. The relative fracture risk was highest for hip and femur. Further study is necessary to elucidate whether this elevated risk is due to the disease, the use of antiepileptic drugs, or both.
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              Bone and calcium metabolism and antiepileptic drugs.

              There is increasing evidence suggesting that epilepsy and its treatment can affect bone mineralization and calcium metabolism. Many studies have shown a significant reduction in bone mineral density in patients treated with classic (phenobarbital, carbamazepine, valproate, etc.) and with new (oxcarbazepine, gabapentin) antiepileptic drugs. In spite of data about the possible effects of the antiepileptic drugs on calcium metabolism, the mechanisms of this important side effect remain to be defined. The abnormalities of calcium metabolism were thought to result from the cytochrome P450 enzyme-inducing properties of some antiepileptic drugs and the resultant reduction in vitamin D levels, but the effect of many medications (e.g., valproate) cannot be readily explained by vitamin D metabolism. In this article, the literature related to the effects of classic and new antiepileptic drugs on bone health and calcium metabolism is reviewed. 2009 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Clin Psychopharmacol Neurosci
                Clin Psychopharmacol Neurosci
                Clinical Psychopharmacology and Neuroscience
                Korean College of Neuropsychopharmacology
                1738-1088
                2093-4327
                February 2016
                29 February 2016
                : 14
                : 1
                : 74-78
                Affiliations
                Department of Neurology, Bakirkoy Education and Research Hospital for Psychiatry, Neurology, and Neurosurgery, Istanbul, Turkey
                Author notes
                Address for correspondence: Betül Tekin Güveli, MD, Department of Neurology, Bakirkoy Education and Research Hospital for Psychiatry, Neurology, and Neurosurgery, Bakırköy, 34147, Istanbul, Turkey, Tel: +90-532-7848273, Fax: +90-212-5729595, E-mail: betultekin2013@ 123456gmail.com
                Article
                cpn-14-074
                10.9758/cpn.2016.14.1.74
                4730931
                26792043
                f4ff8608-82a3-45f0-8f19-f3471185ed06
                Copyright © 2016, Korean College of Neuropsychopharmacology

                This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 May 2015
                : 01 August 2015
                : 25 August 2015
                Categories
                Original Article

                antiepileptic drugs,levetiracetam,oxcarbazepine,25-oh vitamin d3,bone disease

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