nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2016-1S-59-65nnp-624Research ArticleREVIEWSОБЗОРЫMolecular mechanisms responsible for the impact of antiepileptic therapy on bone mineral density of epileptic patientsМолекулярные механизмы влияния антиэпилептической терапии на минеральную плотность костной ткани пациентов с эпилепсиейЖидковаИ. А.ZhidkovaI. A.

Кафедра нервных болезней лечебного факультета

Department of Nervous System Diseases, Faculty of General Medicine

irina.zhidkova@gmail.comКазначееваТ. В.KaznacheevaT. V.

кафедра репродуктивной медицины и хирургии

Department of Reproductive Medicine and Surgery, Faculty of Additional

ДемидоваЕ. Ю.DemidovaE. Yu.

Кафедра нервных болезней лечебного факультета

Department of Nervous System Diseases, Faculty of General Medicine

БерсеневаВ. В.BersenevaV. V.

кафедра репродуктивной медицины и хирургии

Department of Reproductive Medicine and Surgery, Faculty of Additional

ФДПО ГБОУ ВПО «Московский государственный медико-стоматологический университет им. А.И. Евдокимова» Минздрава РоссииРоссияA.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of RussiaRussian Federation20161807201601S5965Copyright © Zhidkova I.A., Kaznacheeva T.V., Demidova E.Y., Berseneva V.V., 20162016Жидкова И.А., Казначеева Т.В., Демидова Е.Ю., Берсенева В.В.Zhidkova I.A., Kaznacheeva T.V., Demidova E.Y., Berseneva V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nnp.ima-press.net/nnp/article/view/624

Antiepileptic drugs (AEDs) may have a negative effect on bone tissue, by increasing the risk of fractures in epileptic patients compared to the general population. Many investigations have shown lower bone mineral density and a higher risk for osteopenia and osteoporosis in patients taking traditional and novel AEDs. Multidrug therapy and the duration of AED intake are associated with the most significant risk for lower bone mineral density. Nevertheless, the molecular mechanisms of action of different AEDs on bone tissue remain little studied.

Противоэпилептические препараты (ПЭП) могут оказывать неблагоприятное влияние на костную ткань, повышая риск развития переломов у пациентов с эпилепсией по сравнению с общей популяцией. Во многих исследованиях показано снижение минеральной плотности костной ткани, увеличение риска развития остеопении и остеопороза у пациентов, получающих традиционные и новые ПЭП. Политерапия и длительность приема ПЭП связаны с наиболее значительным риском снижения минеральной плотности костной ткани. Тем не менее молекулярные механизмы воздействия различных ПЭП на костную ткань остаются малоизученными.

противоэпилептические препаратыэпилепсияминеральная плотность костивитамин Dкальцийantiepileptic drugsepilepsybone mineral densityvitamin DcalciumReferencesSato Y, Kondo I, Ishida S, et al. Decreased bone mass and increased bone turnover with valproate therapy in adults with epilepsy. Neurology. 2001;57:445-9. doi: 10.1212/WNL.57.3.445Sato Y, Kondo I, Ishida S, et al. Decreased bone mass and increased bone turnover with valproate therapy in adults with epilepsy. Neurology. 2001;57:445-9. doi: 10.1212/WNL.57.3.445Eisenberg E, River Y, Shifrin A, Krivoy N. Antiepileptic drugs in the treatment of neuropathic pain. Drugs. 2007;67:1265-89. doi: 10.2165/00003495-200767090-00003Eisenberg E, River Y, Shifrin A, Krivoy N. Antiepileptic drugs in the treatment of neuropathic pain. Drugs. 2007;67:1265-89. doi: 10.2165/00003495-200767090-00003Mintzer S, Boppana P, Toguri J, DeSantis A. Vitamin D levels and bone turnover in epilepsy patients taking carbamazepine or oxcarbazepine. Epilepsia. 2006;47:510-5. doi: 10.1111/j.1528-1167.2006.00460.xMintzer S, Boppana P, Toguri J, DeSantis A. Vitamin D levels and bone turnover in epilepsy patients taking carbamazepine or oxcarbazepine. Epilepsia. 2006;47:510-5. doi: 10.1111/j.1528-1167.2006.00460.xKetter TA, Wang PW, Becker OV, et al. The diverse roles of anticonvulsants in bipolar disorder. Ann Clin Psychiatry. 2003;15:95-108. doi: 10.3109/10401230309085675Ketter TA, Wang PW, Becker OV, et al. The diverse roles of anticonvulsants in bipolar disorder. Ann Clin Psychiatry. 2003;15:95-108. doi: 10.3109/10401230309085675Антонюк МВ. Дифференцированный подход к диагностике и лечению эпилепсии у женщин в климактерии: Дисc. … докт. мед. наук. Москва; 2009 [ Antonyuk MV. Differentsirovannyi podkhod k diagnostike i lecheniyu epilepsii u zhenshchin v klimakterii: Diss. … dokt. med. nauk [Differentiated approach to the diagnosis and treatment of epilepsy in women in menopause: Diss. ... Doct. Med. Sci.]. Moscow; 2009].Антонюк МВ. Дифференцированный подход к диагностике и лечению эпилепсии у женщин в климактерии: Дисc. … докт. мед. наук. Москва; 2009 [ Antonyuk MV. Differentsirovannyi podkhod k diagnostike i lecheniyu epilepsii u zhenshchin v klimakterii: Diss. … dokt. med. nauk [Differentiated approach to the diagnosis and treatment of epilepsy in women in menopause: Diss. ... Doct. Med. Sci.]. Moscow; 2009].Feldkamp J, Becker A, Witte OW, et al. Long-term anticonvulsant therapy leads to low bone mineral density – evidence for direct drug effects of phenytoin and carbamazepine on human osteoblast-like cells. Exp Clin Endocrinol Diabetes. 2000;108:37-43.Feldkamp J, Becker A, Witte OW, et al. Long-term anticonvulsant therapy leads to low bone mineral density – evidence for direct drug effects of phenytoin and carbamazepine on human osteoblast-like cells. Exp Clin Endocrinol Diabetes. 2000;108:37-43.Korinthenberg R, Bukart P, Woefle C, et al. Pharmacology, efficacy and tolerability of potassium bromide in childhood Epilepsy. J Child Neurol. 2007;22:414-8. doi: 10.1177/0883073807302758Korinthenberg R, Bukart P, Woefle C, et al. Pharmacology, efficacy and tolerability of potassium bromide in childhood Epilepsy. J Child Neurol. 2007;22:414-8. doi: 10.1177/0883073807302758Pack AM, Morrell MJ, Marcus R, et al. Bone mass and turnover in women with epilepsy on antiepileptic drug monotherapy. Ann Neurol. 2005;57:252-7. doi: 10.1002/ana.20378Pack AM, Morrell MJ, Marcus R, et al. Bone mass and turnover in women with epilepsy on antiepileptic drug monotherapy. Ann Neurol. 2005;57:252-7. doi: 10.1002/ana.20378Айламазян ЭК, редактор. Гинекология от пубертата до постменопаузы. Москва: МЕДпрессинформ; 2007. 495 с. [Ailamazyan EK, editor. Ginekologiya ot pubertata do postmenopauzy [Gynecology from puberty to menopause]. Moscow: MEDpressinform; 2007. 495 p.].Айламазян ЭК, редактор. Гинекология от пубертата до постменопаузы. Москва: МЕДпрессинформ; 2007. 495 с. [Ailamazyan EK, editor. Ginekologiya ot pubertata do postmenopauzy [Gynecology from puberty to menopause]. Moscow: MEDpressinform; 2007. 495 p.].Andress DL, Ozuna J, Tirschwell D, et al. Antiepileptic drug-induced bone loss in young male patients who have seizures. Arch Neurol. 2002;59:16-78. doi: 10.1001/archneur. 59.5.781Andress DL, Ozuna J, Tirschwell D, et al. Antiepileptic drug-induced bone loss in young male patients who have seizures. Arch Neurol. 2002;59:16-78. doi: 10.1001/archneur. 59.5.781Зоткин ЕГ, Косульникова ЕН. Остеопороз: от организации помощи больным к лечению. Медлайн-Экспресс. 2007;1(190):56-9 [Zotkin EG, Kosul'nikova EN. steoporosis: from the organization of care for patients to treatment. Medlain-Ekspress. 2007;1(190):56-9 (In Russ.)].Зоткин ЕГ, Косульникова ЕН. Остеопороз: от организации помощи больным к лечению. Медлайн-Экспресс. 2007;1(190):56-9 [Zotkin EG, Kosul'nikova EN. steoporosis: from the organization of care for patients to treatment. Medlain-Ekspress. 2007;1(190):56-9 (In Russ.)].Campos LMA, Liphaus BL, Silva CAA, et al. Osteoporosis in childhood and adolescence. J Pediatr (Rio J). 2003;79(6):481-8. doi: 10.2223/jped.1107Campos LMA, Liphaus BL, Silva CAA, et al. Osteoporosis in childhood and adolescence. J Pediatr (Rio J). 2003;79(6):481-8. doi: 10.2223/jped.1107Kaufman KR, Kugler SL, Sachdeo RC. Tiagabine in the management of postencephalitic epilepsy and impulse control disorder. Epilepsy Behav. 2002;(3):190-4. doi: 10.1006/ebeh.2002.0319Kaufman KR, Kugler SL, Sachdeo RC. Tiagabine in the management of postencephalitic epilepsy and impulse control disorder. Epilepsy Behav. 2002;(3):190-4. doi: 10.1006/ebeh.2002.0319Landmark CJ. Antiepileptic drugs in nonepilepsy disorders: relations between mechanisms of action and clinical efficacy. CNS Drugs. 2008;22:27-47. doi: 10.2165/00023210-200822010-00003Landmark CJ. Antiepileptic drugs in nonepilepsy disorders: relations between mechanisms of action and clinical efficacy. CNS Drugs. 2008;22:27-47. doi: 10.2165/00023210-200822010-00003Sussman N, Ettinger AB. Psychotropic properties of antiepileptic drugs. In: Ettinger AB, Kanner AM, editors. Psychiatric issues in epilepsy: a practical guide to diagnosis and treatment. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2007. P. 67-82.Sussman N, Ettinger AB. Psychotropic properties of antiepileptic drugs. In: Ettinger AB, Kanner AM, editors. Psychiatric issues in epilepsy: a practical guide to diagnosis and treatment. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2007. P. 67-82.Schacht E, Richy F, Reginster JY. The therapeutic effects of alfacalcidol on bone strength, muscle metabolism and prevention of falls and fractures. J Musculoskelet Neuronal Interact. 2005;5(3):273-84.Schacht E, Richy F, Reginster JY. The therapeutic effects of alfacalcidol on bone strength, muscle metabolism and prevention of falls and fractures. J Musculoskelet Neuronal Interact. 2005;5(3):273-84.Steingrimsdottir L, Gunnarsson O, Indridason OS, et al. Relationship between serum parathyroid hormone levels, vitamin D sufficiency, and calcium intake. JAMA. 2005;294(18):2336-41. doi: 10.1001/jama.294.18.2336Steingrimsdottir L, Gunnarsson O, Indridason OS, et al. Relationship between serum parathyroid hormone levels, vitamin D sufficiency, and calcium intake. JAMA. 2005;294(18):2336-41. doi: 10.1001/jama.294.18.2336Holic MF. McCollum Award Lecture, 1994: Vitamin D - new horizons for the 21 century. Am J Clin Nutr. 1994;60:610-30.Holic MF. McCollum Award Lecture, 1994: Vitamin D - new horizons for the 21 century. Am J Clin Nutr. 1994;60:610-30.Pack AM. Treatment of epilepsy to optimize bone health. Curr Treat Options Neurol. 2011; 13(4):346-54. doi: 10.1007/s11940-011-0133-xPack AM. Treatment of epilepsy to optimize bone health. Curr Treat Options Neurol. 2011; 13(4):346-54. doi: 10.1007/s11940-011-0133-xPascussi JM, Robert A, Nguyen M, et al. Possible involvement of pregnane X receptorenhanced CYP24 expression in drug-induced osteomalacia. J Clin Invest. 2005;115:177-86. doi: 10.1172/JCI21867Pascussi JM, Robert A, Nguyen M, et al. Possible involvement of pregnane X receptorenhanced CYP24 expression in drug-induced osteomalacia. J Clin Invest. 2005;115:177-86. doi: 10.1172/JCI21867Valsamis HA, Arora SK, Labban B, McFarlane SI. Antiepileptic drugs and bone metabolism. Nutr Metab (Lond). 2006;3:36. doi: 10.1186/1743-7075-3-36Valsamis HA, Arora SK, Labban B, McFarlane SI. Antiepileptic drugs and bone metabolism. Nutr Metab (Lond). 2006;3:36. doi: 10.1186/1743-7075-3-36Larsen ER, Mosekilde L, Foldspang A. Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: A pragmatic populationbased 3-year intervention study. J Bone Miner Res. 2004;19:270-8. doi: 10.1359/jbmr.0301240Larsen ER, Mosekilde L, Foldspang A. Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: A pragmatic populationbased 3-year intervention study. J Bone Miner Res. 2004;19:270-8. doi: 10.1359/jbmr.0301240Koch HU, Kraft D, von Herrath D, Schaefer K. Influence of diphenylhydantoin and phenobarbital on intestinal calcium transport in the rat. Epilepsia. 1972;13:829. doi: 10.1111/j.1528-1157.1972.tb05167.xKoch HU, Kraft D, von Herrath D, Schaefer K. Influence of diphenylhydantoin and phenobarbital on intestinal calcium transport in the rat. Epilepsia. 1972;13:829. doi: 10.1111/j.1528-1157.1972.tb05167.xMosekilde L, Hansen HH, Christensen MS, et al. Fractional intestinal calcium absorption in epileptics on anticonvulsant therapy. Short-term effect of 1,25 dihydroxycholecalciferol and 25-hydroxycholecalciferol. Acta Med Scand. 1979;205:405. doi: 10.1111/j.0954-6820.1979.tb06073.xMosekilde L, Hansen HH, Christensen MS, et al. Fractional intestinal calcium absorption in epileptics on anticonvulsant therapy. Short-term effect of 1,25 dihydroxycholecalciferol and 25-hydroxycholecalciferol. Acta Med Scand. 1979;205:405. doi: 10.1111/j.0954-6820.1979.tb06073.xTakahashi A, Onodera K, Shinoda H, Mayanagi H. Phenytoin and its metabolite, 5-(4-hydroxyphenyl)-5-phenylhydantoin, show bone resorption in cultured neonatal mouse calvaria. Jpn J Pharmacol. 2000;82:82. doi: 10.1254/jjp.82.82Takahashi A, Onodera K, Shinoda H, Mayanagi H. Phenytoin and its metabolite, 5-(4-hydroxyphenyl)-5-phenylhydantoin, show bone resorption in cultured neonatal mouse calvaria. Jpn J Pharmacol. 2000;82:82. doi: 10.1254/jjp.82.82Onodera K, Takahashi A, Sakurada S, Okano Y. Effects of phenytoin and/or vitamin K2 (menatetrenone) on bone mineral density in the tibiae of growing rats. Life Sci. 2002;70:15-33. doi: 10.1016/S0024-3205(01)01522-3Onodera K, Takahashi A, Sakurada S, Okano Y. Effects of phenytoin and/or vitamin K2 (menatetrenone) on bone mineral density in the tibiae of growing rats. Life Sci. 2002;70:15-33. doi: 10.1016/S0024-3205(01)01522-3Vernillo AT, Rifkin BR, Hauschka PV. Phenytoin affects osteocalcin secretion from osteoblastic rat osteosarcoma 17/2.8 cells in culture. Bone. 1990;11:309. doi: 0.1016/8756- 3282(90)90085-DVernillo AT, Rifkin BR, Hauschka PV. Phenytoin affects osteocalcin secretion from osteoblastic rat osteosarcoma 17/2.8 cells in culture. Bone. 1990;11:309. doi: 0.1016/8756- 3282(90)90085-DElliott JO, Jacobson MP, Haneef Z. Homocysteine and bone loss in epilepsy. Seizure. 2007;16:22. doi: 10.1016/j.seizure.2006.10.001Elliott JO, Jacobson MP, Haneef Z. Homocysteine and bone loss in epilepsy. Seizure. 2007;16:22. doi: 10.1016/j.seizure.2006.10.001Tsukahara H, Kimura K, Todoroki Y, et al. Bone mineral status in ambulatory pediatric patients on long-term antiepileptic drug therapy. Pediatr Int. 2002;44:247-53. doi: 10.1046/j.1442-200X.2002.01561.xTsukahara H, Kimura K, Todoroki Y, et al. Bone mineral status in ambulatory pediatric patients on long-term antiepileptic drug therapy. Pediatr Int. 2002;44:247-53. doi: 10.1046/j.1442-200X.2002.01561.xTekgul H, Serdaroglu G, Huseyinov A, Gц kben S. Bone mineral status in pediatric outpatients on antiepileptic drug monotherapy. J Child Neurol. 2006;21:411-4.Tekgul H, Serdaroglu G, Huseyinov A, Gц kben S. Bone mineral status in pediatric outpatients on antiepileptic drug monotherapy. J Child Neurol. 2006;21:411-4.Vestergaard P, Rejnmark L, Mosekilde L. Anxiolytics and sedatives and risk of fractures: effects of half-life. Calcif Tissue Int. 2008;82: 34-43. doi: 10.1007/s00223-007-9095-0Vestergaard P, Rejnmark L, Mosekilde L. Anxiolytics and sedatives and risk of fractures: effects of half-life. Calcif Tissue Int. 2008;82: 34-43. doi: 10.1007/s00223-007-9095-0Pack AM, Morrell MJ, Randall A, et al. Bone health in young women with epilepsy after one year of antiepileptic drug monotherapy. Neurology. 2008;29:1586-93. doi: 10.1212/01.wnl.0000310981.44676.dePack AM, Morrell MJ, Randall A, et al. Bone health in young women with epilepsy after one year of antiepileptic drug monotherapy. Neurology. 2008;29:1586-93. doi: 10.1212/01.wnl.0000310981.44676.deEl-Hajj Fuleihan G, Dib L, Yamout B, et al. Predictors of bone density in ambulatory patients on antiepileptic drugs. Bone. 2008;43:149-55. doi: 10.1016/j.bone. 2008.03.002El-Hajj Fuleihan G, Dib L, Yamout B, et al. Predictors of bone density in ambulatory patients on antiepileptic drugs. Bone. 2008;43:149-55. doi: 10.1016/j.bone. 2008.03.002Petty SJ, Paton LM, O'Brien TJ, et al. Effect of antiepileptic medication on bone mineral measures. Neurology. 2005;65:1358-65. doi: 10.1212/01.wnl.0000180910.72487.18Petty SJ, Paton LM, O'Brien TJ, et al. Effect of antiepileptic medication on bone mineral measures. Neurology. 2005;65:1358-65. doi: 10.1212/01.wnl.0000180910.72487.18Kim SH, Lee JW, Choi KG, et al. A 6-month longitudinal study of bone mineral density with antiepileptic drug monotherapy. Epilepsy Behav. 2007;10:291-5. doi: 10.1016/j.yebeh.2006.11.007Kim SH, Lee JW, Choi KG, et al. A 6-month longitudinal study of bone mineral density with antiepileptic drug monotherapy. Epilepsy Behav. 2007;10:291-5. doi: 10.1016/j.yebeh.2006.11.007Tjellesen L, Christiansen C. Serum vitamin D metabolites in epileptic patients treated with 2 different anti-convulsants. Acta Neurol Scand. 1982;66:335-41. doi: 10.1111/j.1600- 0404.1982.tb06853.xTjellesen L, Christiansen C. Serum vitamin D metabolites in epileptic patients treated with 2 different anti-convulsants. Acta Neurol Scand. 1982;66:335-41. doi: 10.1111/j.1600- 0404.1982.tb06853.xKumandas S, Koklu E, Gemes H, et al. Effect of carbamezapine and valproic acid on bone mineral density, IGF-I and IGFBP-3. J Pediatr Endocrinol Metab. 2006;19(4):529-34.Kumandas S, Koklu E, Gemes H, et al. Effect of carbamezapine and valproic acid on bone mineral density, IGF-I and IGFBP-3. J Pediatr Endocrinol Metab. 2006;19(4):529-34.Verrotti A, Greco R, Latini G, Morgese G, Chiarelli F. Increased bone turnover in prepubertal, pubertal, and postpubertal patients receiving carbamazepine. Epilepsia. 2002;43:1488-92. doi: 10.1046/j.1528-1157.2002.13002.xVerrotti A, Greco R, Latini G, Morgese G, Chiarelli F. Increased bone turnover in prepubertal, pubertal, and postpubertal patients receiving carbamazepine. Epilepsia. 2002;43:1488-92. doi: 10.1046/j.1528-1157.2002.13002.xVerrotti A, Greco R, Morgese G, Chiarelli F. Increased bone turnover in epileptic patients treated with carbamazepine. Ann Neurol. 2000;47(3):385-8. doi: 10.1002/1531- 8249(200003)47:3<385::AID-ANA18>3.0. CO;2-WVerrotti A, Greco R, Morgese G, Chiarelli F. Increased bone turnover in epileptic patients treated with carbamazepine. Ann Neurol. 2000;47(3):385-8. doi: 10.1002/1531- 8249(200003)47:3<385::AID-ANA18>3.0. CO;2-WСелютина ТВ. Состояние минеральной плотности костной ткани у больных эпилепсией: Дисс. … канд. мед. наук. Москва; 2008 [Selyutina TV. Sostoyanie mineral'noi lotnosti kostnoi tkani u bol'nykh epilepsiei: Diss. … kand. med. nauk [Status of bone mineral density in patients with epilepsy: Diss. ... Cand. Med. Sci.]. Moscow; 2008].Селютина ТВ. Состояние минеральной плотности костной ткани у больных эпилепсией: Дисс. … канд. мед. наук. Москва; 2008 [Selyutina TV. Sostoyanie mineral'noi lotnosti kostnoi tkani u bol'nykh epilepsiei: Diss. … kand. med. nauk [Status of bone mineral density in patients with epilepsy: Diss. ... Cand. Med. Sci.]. Moscow; 2008].Заседателева ИЮ. Особенности минерального обмена и гормонального статуса у больных эпилепсией: Дисс. … канд. мед. наук. Санкт-Петербург; 2005 [Zasedateleva IYu. Osobennosti mineral'nogo obmena i gormonal'nogo statusa u bol'nykh epilepsiei: Diss. … kand. med. nauk [Features of mineral metabolism and hormonal status in patients with epilepsy: Diss. ... Cand. Med. Sci.]. St. Petersburg; 2005].Заседателева ИЮ. Особенности минерального обмена и гормонального статуса у больных эпилепсией: Дисс. … канд. мед. наук. Санкт-Петербург; 2005 [Zasedateleva IYu. Osobennosti mineral'nogo obmena i gormonal'nogo statusa u bol'nykh epilepsiei: Diss. … kand. med. nauk [Features of mineral metabolism and hormonal status in patients with epilepsy: Diss. ... Cand. Med. Sci.]. St. Petersburg; 2005].Valimaki MJ, Tiihonen M, Laitinen K, et al. Bone mineral density measured by dual- energy X-ray absorptiometry and novel markers of bone formation and resorption in patients on antiepileptic drugs. J Bone Miner Res. 1994;9:631-7.Valimaki MJ, Tiihonen M, Laitinen K, et al. Bone mineral density measured by dual- energy X-ray absorptiometry and novel markers of bone formation and resorption in patients on antiepileptic drugs. J Bone Miner Res. 1994;9:631-7.Ensrud KE, Walczak TS, Blackwell T, et al. Antiepileptic drug use increases rates of bone loss in older women: a prospective study. Neurology. 2004;62:2051-7. doi: 10.1212/01.WNL.0000125185.74276.D2Ensrud KE, Walczak TS, Blackwell T, et al. Antiepileptic drug use increases rates of bone loss in older women: a prospective study. Neurology. 2004;62:2051-7. doi: 10.1212/01.WNL.0000125185.74276.D2Stephen LJ, Sills GJ, Leach JP, et al. Sodium valproate versus lamotrigine: a randomized comparison of efficacy, tolerabil-ity and effects on circulating androgenic hormones in newly diagnosed epilepsy. Epilepsy Res. 2007;75:9122-9. doi: 10.1016/j.eplepsyres. 2007.04.009Stephen LJ, Sills GJ, Leach JP, et al. Sodium valproate versus lamotrigine: a randomized comparison of efficacy, tolerabil-ity and effects on circulating androgenic hormones in newly diagnosed epilepsy. Epilepsy Res. 2007;75:9122-9. doi: 10.1016/j.eplepsyres. 2007.04.009Pack AM, Olarte LS, Morrell MJ, et al. Bone mineral density in an outpatient population receiving enzyme-inducing antiepileptic drugs. Epilepsy Behav. 2003;4(2):169-74. doi: 10.1016/S1525-5050(03)00036-2Pack AM, Olarte LS, Morrell MJ, et al. Bone mineral density in an outpatient population receiving enzyme-inducing antiepileptic drugs. Epilepsy Behav. 2003;4(2):169-74. doi: 10.1016/S1525-5050(03)00036-2Boluk A, Guzelipek M, Savli H, et al. The effect of valproate on bone mineral density in adult epileptic patients. Pharmacol Res. 2004;50:93-7. doi: 10.1016/j.phrs.2003.11.011Boluk A, Guzelipek M, Savli H, et al. The effect of valproate on bone mineral density in adult epileptic patients. Pharmacol Res. 2004;50:93-7. doi: 10.1016/j.phrs.2003.11.011Babayigit A, Dirik E, Bober E, Cakmakci H. Adverse effects of antiepileptic drugs on bone mineral density. Pediatr Neurol. 2006;35:177-81. doi: 10.1016/j.pedatrnerol. 2006.03.004Babayigit A, Dirik E, Bober E, Cakmakci H. Adverse effects of antiepileptic drugs on bone mineral density. Pediatr Neurol. 2006;35:177-81. doi: 10.1016/j.pedatrnerol. 2006.03.004Erbayat Altay E, Serdaroglu A, Tь mer L, et al. Evaluation of bone mineral metabolism in children receiving carbamazepine and valproic acid. J Pediatr Endocrinol Metab. 2000;13:33-9. doi: 10.1515/JPEM.2000.13.7.933Erbayat Altay E, Serdaroglu A, Tь mer L, et al. Evaluation of bone mineral metabolism in children receiving carbamazepine and valproic acid. J Pediatr Endocrinol Metab. 2000;13:33-9. doi: 10.1515/JPEM.2000.13.7.933Cansu A, Yesilkaya E, Serdaroglu A, et al. Evaluation of bone turnover in epileptic children using oxcarbazepine. Pediatr Neurol. 2008;39:266-71. doi: 0.1016/j.pediatrneurol. 2008.07.001Cansu A, Yesilkaya E, Serdaroglu A, et al. Evaluation of bone turnover in epileptic children using oxcarbazepine. Pediatr Neurol. 2008;39:266-71. doi: 0.1016/j.pediatrneurol. 2008.07.001Andreasen AH, Brosen K, Damkier P. A comparative pharmacokinetic study in healthy volunteers of the effect of carbamazepine and oxcarbazepine on cyp3a4. Epilepsia. 2007;48:490-6. doi: 10.1111/j.1528- 1167.2007.00924.xAndreasen AH, Brosen K, Damkier P. A comparative pharmacokinetic study in healthy volunteers of the effect of carbamazepine and oxcarbazepine on cyp3a4. Epilepsia. 2007;48:490-6. doi: 10.1111/j.1528- 1167.2007.00924.xCetinkaya Y, Kurtulmus YS, Tutkavul K, Tireli H. The effect of oxcarbazepine on bone metabolism. Acta Neurol Scand. 2009;120: 170-5. doi: 10.1111/j.1600-0404.2008.01148.xCetinkaya Y, Kurtulmus YS, Tutkavul K, Tireli H. The effect of oxcarbazepine on bone metabolism. Acta Neurol Scand. 2009;120: 170-5. doi: 10.1111/j.1600-0404.2008.01148.xMirza N, Marson AG, Pirmohamed M. Effect of topiramate on acidbase balance: extent, mechanism and effects. Br J Clin Pharmacol. 2009;68:655-61. doi: 10.1111/j.1365-2125.2009.03521.xMirza N, Marson AG, Pirmohamed M. Effect of topiramate on acidbase balance: extent, mechanism and effects. Br J Clin Pharmacol. 2009;68:655-61. doi: 10.1111/j.1365-2125.2009.03521.xVacek TP, Kalani A, Voor MJ, et al. The role of homocysteine in bone remodeling. Clin Chem Lab Med. 2013;51:579-90. doi: 10.1515/cclm-2012-0605Vacek TP, Kalani A, Voor MJ, et al. The role of homocysteine in bone remodeling. Clin Chem Lab Med. 2013;51:579-90. doi: 10.1515/cclm-2012-0605Zhang J, Wang KX, Wie Y, et al. Effect of topiramate and carbamazepine on bone metabolism in children with epilepsy. Zhongguo Dang Dai Er Ke Za Zhi = Chin J Contemp Paediatr. 2010;12:96-8 (In Chin.).Zhang J, Wang KX, Wie Y, et al. Effect of topiramate and carbamazepine on bone metabolism in children with epilepsy. Zhongguo Dang Dai Er Ke Za Zhi = Chin J Contemp Paediatr. 2010;12:96-8 (In Chin.).Heo K, Rhee Y, Lee HW, et al. The effect of topiramate monotherapy on bone mineral density and markers of bone and mineral metabolism in premenopausal women with epilepsy. Epilepsia. 2011;52:1884-9. doi: 10.1111/j.1528-1167.2011.03131.xHeo K, Rhee Y, Lee HW, et al. The effect of topiramate monotherapy on bone mineral density and markers of bone and mineral metabolism in premenopausal women with epilepsy. Epilepsia. 2011;52:1884-9. doi: 10.1111/j.1528-1167.2011.03131.xCereghino JJ, Biton V, Abou-Khalil B, et al. Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial. Neurology. 2000;55:236-42. doi: 10.1212/WNL.55.2.236Cereghino JJ, Biton V, Abou-Khalil B, et al. Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial. Neurology. 2000;55:236-42. doi: 10.1212/WNL.55.2.236Карлов ВА, Власов ПН. Результаты двухлетнего применения кеппры для лечения эпилепсии у взрослых. Журнал неврологии и психиатрии им. С.С. Корсакова. 2006;106(7):24-30 [Karlov VA, Vlasov PN. The results of the two-year use of Keppra in the treatment of epilepsy in adults. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova =S.S. Korsakov Journal of Neurology and Psychiatry. 2006;106(7):24-30 (In Russ.)].Карлов ВА, Власов ПН. Результаты двухлетнего применения кеппры для лечения эпилепсии у взрослых. Журнал неврологии и психиатрии им. С.С. Корсакова. 2006;106(7):24-30 [Karlov VA, Vlasov PN. The results of the two-year use of Keppra in the treatment of epilepsy in adults. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova =S.S. Korsakov Journal of Neurology and Psychiatry. 2006;106(7):24-30 (In Russ.)].Карлов ВА, Власов ПН, Комелькова ЕГ, Шахабасова ЗС. Длительная монотерапия леветирацетамом парциальной эпилепсии у взрослых. Журнал неврологии и психиатрии им. С.С. Корсакова. 2010;(2):15-20 [Karlov VA, Vlasov PN, Komel'kova EG, Shakhabasova ZS. Long-term monotherapy with levetiracetam partial epilepsy in adults. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2010;(2):15-20 (In Russ.)].Карлов ВА, Власов ПН, Комелькова ЕГ, Шахабасова ЗС. Длительная монотерапия леветирацетамом парциальной эпилепсии у взрослых. Журнал неврологии и психиатрии им. С.С. Корсакова. 2010;(2):15-20 [Karlov VA, Vlasov PN, Komel'kova EG, Shakhabasova ZS. Long-term monotherapy with levetiracetam partial epilepsy in adults. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2010;(2):15-20 (In Russ.)].Dooley M, Plosker GL. Levetiracetam: a review of its adjunctive use in the management of partial onset seizures. Drugs. 2000;60:871-93. doi: 10.2165/00003495- 200060040-00004Dooley M, Plosker GL. Levetiracetam: a review of its adjunctive use in the management of partial onset seizures. Drugs. 2000;60:871-93. doi: 10.2165/00003495- 200060040-00004Blais L, Sheehy O, St Hilaire JM, et al. Economic evaluation of levetiracetam as an addon therapy in patients with refractory epilepsy. Pharmacoeconomics. 2005;23:493-503. doi: 10.2165/00019053-200523050-00008Blais L, Sheehy O, St Hilaire JM, et al. Economic evaluation of levetiracetam as an addon therapy in patients with refractory epilepsy. Pharmacoeconomics. 2005;23:493-503. doi: 10.2165/00019053-200523050-00008Ali II, Horrigan T., Kellough L, Tietjen GE. Measurement of bone mineral density in patients on levetiracetam monotherapy. Am Epilepsy Soc Abstr. 2006;(2):150.Ali II, Horrigan T., Kellough L, Tietjen GE. Measurement of bone mineral density in patients on levetiracetam monotherapy. Am Epilepsy Soc Abstr. 2006;(2):150.Nissen-Meyer LS, Svalheim S, Tauboll E, et al. Levetiracetam, phenytoin, and valproate act differently on rat bone mass, structure, and metabolism. Epilepsia. 2007;48:1850-60. doi: 10.1111/j.1528-1167.2007.01176.xNissen-Meyer LS, Svalheim S, Tauboll E, et al. Levetiracetam, phenytoin, and valproate act differently on rat bone mass, structure, and metabolism. Epilepsia. 2007;48:1850-60. doi: 10.1111/j.1528-1167.2007.01176.xBeniczky SA, Viken J, Jensen LT, Andersen NB. Bone mineral density in adult patients treated with various antiepileptic drugs. Seizure. 2012;21:471-2. doi: 10.1016/j.seizure.2012.04.002Beniczky SA, Viken J, Jensen LT, Andersen NB. Bone mineral density in adult patients treated with various antiepileptic drugs. Seizure. 2012;21:471-2. doi: 10.1016/j.seizure.2012.04.002Fekete S, Simko J, Gradosova I, et al. The effect levetiracetam on rat bone mass, structure and metabolism. Epilepsy Res. 2013;13:217-9. doi: 10.1016/j.eplepsyres.2013.08.012Fekete S, Simko J, Gradosova I, et al. The effect levetiracetam on rat bone mass, structure and metabolism. Epilepsy Res. 2013;13:217-9. doi: 10.1016/j.eplepsyres.2013.08.012Aksoy D, Atakli D, Apraci B, et al. Effect of oxcarbazehine and levetiracetam as a monotherapy on calcium and vitamin D metabolism. Abstract from the 11 European Congress on Epileptology, Stockholm, Sweden; Jun 29-Jul 3 2014. Epilepsia. 2014;55(Suppl 2):44.Aksoy D, Atakli D, Apraci B, et al. Effect of oxcarbazehine and levetiracetam as a monotherapy on calcium and vitamin D metabolism. Abstract from the 11 European Congress on Epileptology, Stockholm, Sweden; Jun 29-Jul 3 2014. Epilepsia. 2014;55(Suppl 2):44.Sheth RD, Hermann BP. Bone mineral density with lamotrigine monotherapy for epilepsy. Pediatr Neurol. 2007;37:250-4. doi: 10.1016/j.pediatrneurol.2007.05.018Sheth RD, Hermann BP. Bone mineral density with lamotrigine monotherapy for epilepsy. Pediatr Neurol. 2007;37:250-4. doi: 10.1016/j.pediatrneurol.2007.05.018Takahashi A, Onodera K, Kamei J, et al. Effects of chronic administration of zonisamide, an antiepileptic drug, on bone mineral density and their prevention with alfacalcidol in growing rats. J Pharmacol Sci. 2003;91:313-8. doi: 10.1254/jphs.91.313Takahashi A, Onodera K, Kamei J, et al. Effects of chronic administration of zonisamide, an antiepileptic drug, on bone mineral density and their prevention with alfacalcidol in growing rats. J Pharmacol Sci. 2003;91:313-8. doi: 10.1254/jphs.91.313Morijiri Y, Sato T. Factors causing rickets in institutionalised handicapped children on anticonvulsant therapy. Arch Dis Child. 1981;56:446-9. doi: 10.1136/adc.56.6.446Morijiri Y, Sato T. Factors causing rickets in institutionalised handicapped children on anticonvulsant therapy. Arch Dis Child. 1981;56:446-9. doi: 10.1136/adc.56.6.446Phabphal K, Geater A, Leelawattana R, et al. Prevalence and risk factors of low bone mineral density and 25-hydroxyvitamin D status in young healthy epileptic adult patients in a tropical Asian country taking antiepileptic drug. Bone. 2009;45:232-7. doi: 10.1016/j.bone.2009.04.235Phabphal K, Geater A, Leelawattana R, et al. Prevalence and risk factors of low bone mineral density and 25-hydroxyvitamin D status in young healthy epileptic adult patients in a tropical Asian country taking antiepileptic drug. Bone. 2009;45:232-7. doi: 10.1016/j.bone.2009.04.235Воронкова КВ, Петрухин АС, Пылаева ОА, Холин АА. Рациональная антиэпилептическая фармакотерапия (руководство для врачей). Москва: БИНОМ; 2008. 191 с. [Voronkova KV, Petrukhin AS, Pylaeva OA, Kholin AA. Ratsional'naya antiepilepticheskaya farmakoterapiya (rukovodstvo dlya vrachei) [Rational antiepileptic pharmacotherapy (manual for physicians)]. Moscow: BINOM; 2008. 191 p.].Воронкова КВ, Петрухин АС, Пылаева ОА, Холин АА. Рациональная антиэпилептическая фармакотерапия (руководство для врачей). Москва: БИНОМ; 2008. 191 с. [Voronkova KV, Petrukhin AS, Pylaeva OA, Kholin AA. Ratsional'naya antiepilepticheskaya farmakoterapiya (rukovodstvo dlya vrachei) [Rational antiepileptic pharmacotherapy (manual for physicians)]. Moscow: BINOM; 2008. 191 p.].Persson HB, Alberts KA, Farahmand BY, Tomson T. Risk of extremity fractures in adult outpatients with epilepsy. Epilepsia. 2002;43:768-72. doi: 10.1046/j.1528- 1157.2002.15801.xPersson HB, Alberts KA, Farahmand BY, Tomson T. Risk of extremity fractures in adult outpatients with epilepsy. Epilepsia. 2002;43:768-72. doi: 10.1046/j.1528- 1157.2002.15801.xSouverein PC, Webb DJ, Weil JG, et al. Use of antiepileptic drugs and risk of fractures: case-control study among patients with epilepsy. Neurology. 2006;66:1318-24. doi: 10.1212/01.wnl.0000210503.89488.88Souverein PC, Webb DJ, Weil JG, et al. Use of antiepileptic drugs and risk of fractures: case-control study among patients with epilepsy. Neurology. 2006;66:1318-24. doi: 10.1212/01.wnl.0000210503.89488.88Blum D. Total impact of epilepsy: biological, psychological, social, and economic aspects. Barrow Quarterly. 1999;15:1-20.Blum D. Total impact of epilepsy: biological, psychological, social, and economic aspects. Barrow Quarterly. 1999;15:1-20.

The authors declare that there are no conflicts of interest present.