Bone mineral metabolism changes in epileptic children receiving valproic acid

Öner, Naci; Kaya, Meryem; Karasalihoğlu, Serap; Karaca, Halıt; Çeltik, Coşkun; Tütüncüler, Filiz

doi:10.1111/j.1440-1754.2004.00431.x

Cited by 78 publications

(74 citation statements)

References 20 publications

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“…AEDs increase catabolism of 25-hydroxyvitamin D by induction of the hepatic P-450 enzyme system, leading to relative hypocalcemia, increased levels of parathyroid hormone (PTH), and subsequent low BMD (Dent et al, 1970;Keck et al, 1982;Chung and Ahn, 1994). However, some studies have suggested a significant reduction in BMD with non-enzymeinducing AEDs (Oner et al, 2004;Petty et al, 2005). Other environmental and epidemiological parameters including age, sex, diet, and mobility may also affect mineral metabolism (Pack and Morrell, 2001), suggesting a multifactorial etiology.…”

Section: Introductionmentioning

confidence: 99%

Effects of antiepileptic drugs on bone mineral density and bone metabolism in children: A meta-analysis

Zhang

Zheng

Zhu

et al. 2015

J. Zhejiang Univ. Sci. B

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Abstract:Objective: The aim of our meta-analysis was to assess the effects of antiepileptic drugs on bone mineral density and bone metabolism in epileptic children. Methods: Searches of PubMed and Web of Science were undertaken to identify studies evaluating the association between antiepileptic drugs and bone mineral density and bone metabolism. Results: A total of 22 studies with 1492 subjects were included in our research. We identified: (1) a reduction in bone mineral density at lumbar spine (standardized mean difference ( Our meta-analysis suggests that treatment with antiepileptic drugs may be associated with decreased bone mineral density in epileptic children.

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Section: Introductionmentioning

confidence: 99%

Effects of antiepileptic drugs on bone mineral density and bone metabolism in children: A meta-analysis

Zhang

Zheng

Zhu

et al. 2015

J. Zhejiang Univ. Sci. B

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“…These drugs alter the metabolism and cause osteopenia and osteomalacia by leading clearance of vitamin D (29). Anticonvulsant drugs cause changes in bone metabolism and calcium levels and these drugs may lead to a decrease in bone mass (39). In previous studies increased ALP activities were reported in serum and different tissues (40,41).…”

Section: Discussionmentioning

confidence: 99%

Edaravone ameliorates valproate-induced gingival toxicity by reducing oxidative-stress, inflammation and tissue damage

Oktay¹,

Alev²,

Öztürk³

et al. 2016

Marmara Pharm J

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ABSTRACTvalproic acid (2-n-propylpentanoic acid, vPA), the most widely used antiepileptic drug, has potential adverse effects and it can disrupt the oxidant and antioxidant balance. Edaravone (3-methyl-1-phenyl-2-pyrazoline-5-one, EDA) is a potent free radical scavenger. In this study, the effect of EDA on gingiva in vPA induced toxicity was investigated. female Sprague Dawley rats were randomly divided into four groups: control group, EDA (30 mg/kg/day) given group, vPA (0.5 g/kg/day) given group, and vPA+EDA (in same dose and time) given group. EDA and vPA were given intraperitoneally for seven days. Total protein, lipid peroxidation (LPO), sialic acid (SA) and reduced glutathione (GSH) levels and catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), myeloperoxidase (mPO), alkaline phosphatase (ALP), acid phosphatase (ACP), sodium potassium ATPase (na + /K + -ATPase) and tissue factor (Tf) activities were determined in gingiva homogenates. The vPA-induced increases were statistically significant for mPO (p<0.01), ACP (p<0.01), na + /K + -ATPase (p<0.05) and Tf (p<0.01) activities, but not for LPO level and ALP activities. EDA treatment markedly blunted all such elevated anomalies. Conclusively, vPA induced oxidative and inflammatory gingival tissue damage, reactions that were appreciably reversed by concurrent administration of EDA.

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“…Increases in serum levels of total alkaline phosphatase have been reported in several studies 28,35,37 . In two studies, the osteocalcin levels of the patient group were significantly higher than the control group 5,27,36 . Urine values of deoxypyridinoline showed no significant difference between epileptic and healthy children 27,38,39 .…”

Section: Parameters/ Groupsmentioning

confidence: 94%

“…Some studies found results suggesting that serum calcium concentrations may be significantly lower in patients receiving VPA 28,33,34 . In many studies, serum levels of intact parathyroid hormone were within the normal range 28,30,32,34,35,36 . Increases in serum levels of total alkaline phosphatase have been reported in several studies 28,35,37 .…”

Section: Parameters/ Groupsmentioning

confidence: 99%

“…However, a previously-reported cross-sectional study accomplished with different groups of epileptic patients treated with six different AEDs including; carbamazepine, oxcarbazepine, VPA, LTG, topiramate and LEV demonstrated that the patient group treated with AED polytherapies showed nonsignificant changes in bone mineral density 16 . Long-term antiepileptic treatment with VPA may cause osteopenia in both sexes 5,28,33,34,35,36 . Many authors have noticed a significant reduction of bone marrow density 5,28,32,34,35 .…”

Section: Parameters/ Groupsmentioning

confidence: 99%

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Levetiracetam and lamotrigine effects as mono- and polytherapy on bone mineral density in epileptic patients

El-Haggar

Mostafa

Allah

et al. 2018

Arq. Neuro-Psiquiatr.

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The purpose of this study was to determine the effect of lamotrigine (LTG) and levetiracetam (LEV) as mono- and polytherapy on biochemical markers of bone turnover and bone mineral density in Egyptian adult patients with epilepsy. Methods Forty-eight patients were divided into four groups: two received monotherapy of either LTG or LEV, and the other two groups received polytherapy comprising (valproate [VPA] + LTG or VPA + LEV). Thirty matched healthy participants were included in the study. Participants completed a nutritional and physical activity questionnaire. Biochemical markers of bone and mineral metabolism and bone mineral density of the lumbar spine were measured at baseline and at six months. Results In the LEV monotherapy group, the bone formation markers showed a significant decrease in serum alkaline phosphatase and serum osteocalcin levels while the bone resorption marker showed a significant increase in urinary deoxypyridinoline levels. After six months of treatment, bone mineral density showed a significant decrease in all treated groups, while among monotherapy groups, this significant decrease was more prevalent in the LEV monotherapy group compared with the LTG monotherapy group. Furthermore, there was significant negative correlation between urinary deoxypyridinoline levels and bone mineral density in the LEV monotherapy group. Conclusion Using new generation antiepileptics, LEV monotherapies and polytherapy showed harmful effects on bone but LTG did not.

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Bone mineral metabolism changes in epileptic children receiving valproic acid

Abstract: Long-term and high dose VPA therapy may cause osteopenia, primarily in younger epileptic children. These patients should be followed closely by BMD measurements.

Cited by 78 publications

References 20 publications

Effects of antiepileptic drugs on bone mineral density and bone metabolism in children: A meta-analysis

Effects of antiepileptic drugs on bone mineral density and bone metabolism in children: A meta-analysis

Edaravone ameliorates valproate-induced gingival toxicity by reducing oxidative-stress, inflammation and tissue damage

Levetiracetam and lamotrigine effects as mono- and polytherapy on bone mineral density in epileptic patients

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