Turkiye Klinikleri Journal of Medical Sciences

.: ORIGINAL RESEARCH
The Effects of Levetiracetam as Anti-Epileptic Drug on Bone and Vitamin D Metabolism
Anti-Epileptik İlaç Olarak Levetirasetam'ın Kemik ve D Vitamini Metabolizması Üzerine Etkileri
Şebnem GARİP USTAOĞLUa
aDepartment of Medical Biochemistry, Altınbaş University Faculty of Medicine, İstanbul, TURKEY
Turkiye Klinikleri J Med Sci. 2020;40(3):349-57
doi: 10.5336/medsci.2020-73684
Article Language: EN
Full Text
ABSTRACT
 Objective: Levetiracetam (LEV) is one of the new generations of anti-epileptic drugs. There are controversial results reported in the literature for the effects of LEV on bone metabolism. Some studies reported low bone mineral density (BMD) and vitamin D values with high bone turnover markers, while the others reported no effect on BMD. This study is the first report on elucidation of the mechanism of LEV and seizures on vitamin D and bone metabolism. Material and Methods: 100 mg/kg of LEV in each day was given to rats for twelve weeks. 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D], calcium, bone turnover markers and parathyroid hormone (PTH) were measured by Enzyme-Linked Immunosorbent Assay (ELISA) while the protein levels of anabolic and catabolic enzymes of vitamin D were measured by western blot. Results: The serum levels of calcium, 25(OH)D and 1,25(OH)2D were significantly reduced in all rats, while there were increased amounts of PTH in just LEV-treated rats compared to the control. High bone turnover markers were also observed for drug-treated groups. Both epileptic seizures and LEV increased the amount of 24-hydroxylase; vitamin D catabolic enzyme. Conclusion: Based on the findings of the current study, both the LEV treatment and seizures cause vitamin D deficiency in rats by increasing the 24-hydroxylase amount in epileptic and LEV-treated groups which resulted in the conversion of active vitamin D to an inactive form and reduction in 25(OH)D and 1,25(OH)2D amounts.

Keywords: Bone; levetiracetam; vitamin D; bone turnover markers; parathyroid hormone (PTH); epilepsy; genetically-induced absence seizures; WAG/Rij rats; calcium; 25(OH)D
ÖZET
 Amaç: Levetirasetam (LEV) yeni nesil anti-epileptik ilaçlardan biridir. Literatürde LEV'nin kemik metabolizması üzerindeki etkileri için tartışmalı sonuçlar vardır. Bazı çalışmalar, yüksek kemik döngüsü belirteçleri değeri ile düşük kemik mineral yoğunluğu (BMD) ve D vitamini değerleri bildirirken, diğerleri BMD üzerinde herhangi bir etki bildirmemiştir. Bu çalışma, LEV ve nöbetlerin D vitamini ve kemik metabolizması üzerindeki etki mekanizmasının aydınlatılması üzerine ilk rapordur. Gereç ve Yöntemler: On iki hafta boyunca sıçanlara her gün 100 mg/kg LEV verildi.25-hidroksivitamin D [25(OH)D] ve 1,25-dihidroksivitamin D [1,25(OH)2D], kalsiyum, kemik döngüsü belirteçleri ve paratiroid hormonu (PTH) Enzim bağlantılı immunosorbent testi (ELISA) ile, D vitamini anabolik ve katabolik enzimlerinin protein seviyeleri Western Blot tekniği ile ölçüldü. Bulgular: Serum kalsiyum, 25(OH)D ve 1,25(OH)2D seviyeleri tüm sıçanlarda önemli ölçüde azalırken, sadece LEV ile tedavi edilen sıçanlarda kontrole kıyasla artan miktarlarda PTH değeri vardı. İlaçla tedavi edilen gruplar için yüksek kemik döngüsü belirteçleri de gözlenmiştir. Hem epileptik nöbetler hem de LEV, D vitamini katabolik enzimi olan 24-hidroksilazın miktarını arttırdı. Sonuç: Mevcut çalışmanın bulgularına dayanarak, hem LEV tedavisi hem de nöbetler, epileptik ve LEV ile tedavi edilen gruplarda 24-hidroksilaz miktarını artırarak ve buna bağlı olarak aktif D vitamininin aktif olmayan bir forma dönüştürülmesine ve 25(OH)D ve 1,25(OH)2D miktarlarında azalmayı sağlayarak sıçanlarda D vitamini eksikliğine neden olmaktadır.

Anahtar Kelimeler: Kemik; levetiracetam; vitamin D; kemik döngüsü belirteçleri; paratiroid hormone (PTH); epilepsi; genetik olarak indüklenen absans nöbetleri; WAG/Rij sıçanlar; kalsiyum; 25(OH)D
REFERENCES:
  1. Iseman MD. [Preventive treatment in tuberculosis]. Iseman MD, ed. Özkara Ş, çeviri editörü. Klinisyenler İçin Tüberküloz Kılavuzu. 1. Baskı. İstanbul: Nobel Tıp Kitabevleri; 2002. p.355-98.
  2. Özkara Ş. [Preventive treatment in tuberculosis]. Özkara Ş, Kılıçaslan Z, editörler. Tüberküloz. İstanbul: Toraks Kitapları; 2010. p.586-97.
  3. Abubakar I, Chakaya J, Maeurer M, Zumla A. Towards optimal treatment for latent Mycobacterium tuberculosis infection. Lancet Respir Med. 2019;7(3):195-7. [Crossref]  [PubMed] 
  4. Haley CA. Treatment of latent tuberculosis infection. Microbiol Spectr. 2017;5(2). [Crossref]  [PubMed] 
  5. Yang J, Lee S, Oh S, Han S, Park SY, Kim Y, et al. The risk of active tuberculosis among individuals living in tuberculosis-affected households in the Republic of Korea, 2015. PLoS One. 2019;14(12):e0225744. [Crossref]  [PubMed]  [PMC] 
  6. World Health Organization. Guidelines on the Management of Latent Tuberculosis Infection. Geneva, Switzerland: World Health Organization; 2015. p.34.
  7. Turkish Republic Ministry of Health. Tüberküloz Tanı ve Tedavi Rehberi. Yayın No: 862. Ankara: Başak Matbaacılık ve Tanıtım Hizmetleri Ltd. Şti.; 2011. p.153.
  8. Turkish Institution of Statistics. [Population and demography]. Temel İstatistikler. www.tuik.gov.tr
  9. Turkish Republic Ministry of Health, Tuberculosis Department, Özkara Ş, Aktaş Z, Özkan S, Ecevit H. Türkiye'de Tüberkülozun Kontrolü İçin Başvuru Kitabı. Ankara: Rekmay Ltd. Şti.; 2003. p.112.
  10. Bishai WR, Chaisson RE. Short-course chemoprophylaxis for tuberculosis. Clin Chest Med. 1997;18(1):115-22. [Crossref]  [PubMed] 
  11. Swift MD, Molella RG, Vaughn AIS, Breeher LE, Newcomb RD, Abdellatif S, et al. Determinants of latent tuberculosis treatment acceptance and completion in healthcare personnel. Clin Infect Dis. 2020;71(2):284-90. [Crossref]  [PubMed] 
  12. Han SS, Lee SJ, Yim JJ, Song JH, Lee EH, Kang YA. Evaluation and treatment of latent tuberculosis infection among healthcare workers in Korea: a multicentre cohort analysis. PLoS One. 2019;14(9):e0222810. [Crossref]  [PubMed]  [PMC] 
  13. Lee EH, Kim SJ, Ha EJ, Park ES, Choi JY, Leem AY, et al. Treatment of latent tuberculous infection among health care workers at a tertiary hospital in Korea. Int J Tuberc Lung Dis. 2018,1;22(11):1336-43. [Crossref]  [PubMed] 
  14. Shedrawy J, Jansson L, Röhl I, Kulane A, Bruchfeld J, Lönnroth K. Quality of life of patients on treatment for latent tuberculosis infection: a mixed-method study in Stockholm, Sweden. Health Qual Life Outcomes. 2019;17(1):158. [Crossref]  [PubMed]  [PMC] 
  15. Santos JC, Silva JB, Rangel MA, Barbosa L, Carvalho I. Preventive therapy compliance in pediatric tuberculosis - A single center experience. Pulmonology. 2020;26(2):78-83. [Crossref]  [PubMed] 
  16. Lam CK, McGinnis Pilote K, Haque A, Burzynski J, Chuck C, Macaraig M. Using video technology to increase treatment completion for patients with latent tuberculosis infection on 3-month isoniazid and rifapentine: an implementation study. J Med Internet Res. 2018;20(11):e287. [Crossref]  [PubMed]  [PMC] 
  17. Cohen A, Mathiasen VD, Schön T, Wejse C7. The global prevalence of latent tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2019;54(3):1900655. [Crossref]  [PubMed] 
  18. Reichler MR, Khan A, Sterling TR, Zhao H, Chen B, Yuan Y, et al; Tuberculosis Epidemiologic Studies Consortium Task Order 2 Team. Risk factors for tuberculosis and effect of preventive therapy among close contacts of persons with infectious tuberculosis. Clin Infect Dis. 2020;70(8):1562-72. [PubMed] 
  19. Huaman MA, Sterling TR. Treatment of latent tuberculosis infection-an update. Clin Chest Med. 2019;40(4):839-48. [Crossref]  [PubMed] 
  20. Chee CBE, Reves R, Zhang Y, Belknap R. Latent tuberculosis infection: opportunities and challenges. Respirology. 2018;23(10):893-900. [Crossref]  [PubMed] 
  21. Kwara A, Herold JS, Machan JT, Carter EJ. Factors associated with failure to complete isoniazid treatment for latent tuberculosis infectionin Rhode Island. Chest. 2008;133(4):862-8. [Crossref]  [PubMed] 
  22. Hirsch-Moverman Y, Daftary A, Franks J, Colson PW. Adherence to treatment for latent tuberculosis infection: systematic review of studies in the US and Canada. Int J Tuberc Lung Dis. 2008;12(11):1235-54. [PubMed] 
  23. Plourde PJ, Basham CA, Derksen S, Schultz J, McCulloch S, Larcombe L, et al. Latent tuberculosis treatment completion rates from prescription drug administrative data. Can J Public Health. 2019;110(6):705-13. [Crossref]  [PubMed]  [PMC] 
  24. Pease C, Zwerling A, Mallick R, Patterson M, Demaio P, Finn S, et al. The latent tuberculosis infection cascade of care in Iqaluit, Nunavut, 2012-2016. BMC Infect Dis. 2019;19(1):890. [Crossref]  [PubMed]  [PMC] 
  25. Séraphin MN, Hsu HC, Chapman HJ, de Andrade Bezerra JL, Johnston L, Yang Y, et al. Timing of treatment interruption among latently infected tuberculosis cases treated with a nine-month course of daily isoniazid: findings from a time to event analysis. BMC Public Health. 2019;19(1):1214. [Crossref]  [PubMed]  [PMC] 
  26. Kawatsu L, Uchimura K, Ohkado A. Trend and treatment status of latent tuberculosis infection patients in Japan - Analysis of Japan TB Surveillance data. PLoS One. 2017;12(11): e0186588. [Crossref]  [PubMed]  [PMC] 
  27. Sentís A, Vasconcelos P, Machado RS, Caylà JA, Guxens M, Peixoto V, et al. Failure to complete treatment for latent tuberculosis infection in Portugal, 2013-2017: geographic, sociodemographic, and medical-associated factors. Eur J Clin Microbiol Infect Dis. 2020;39(4):647-56. [Crossref]  [PubMed] 
  28. Schein YL, Madebo T, Andersen HE, Arnesen TM, Dyrhol-Riise AM, Tveiten H, et al. Treatment completion for latent tuberculosis infection in Norway: a prospective cohort study. BMC Infect Dis. 2018;18(1):587. [Crossref]  [PubMed]  [PMC] 
  29. Noh CS, Kim HI, Choi H, Kim Y, Kim CH, Choi JH, et al. Completion rate of latent tuberculosis infection treatment in patients aged 65 years and older. Respir Med. 2019;157:52-8. [Crossref]  [PubMed] 
  30. Kan B, Kalin M, Bruchfeld J. Completing treatment for latent tuberculosis: patient background matters. Int J Tuberc Lung Dis. 2013;17(5):597-602. [Crossref]  [PubMed] 
  31. Kolsuz M, Ersoy M, Küçükkebapçi C, Metintaş M, Uçgun I, Erginel S. [The evaluation of close contact case of pulmonary tuberculosis patients enrolled to Eskisehir Deliklitas Tuberculosis Control Dispensary]. Tuberk Toraks. 2003;51(3):282-8. [PubMed] 
  32. Kaçmaz Başoğlu Ö, Atasever A. [Treatment of latent tuberculosis infection in tuberculosis dispensaries in İzmir city]. Turkiye Klinikleri Arch Lung. 2005;6(1):14-8.
  33. Dundar C, Oztomurcuk D, Terzi O. Regional success on screening and chemoprophylaxis in contacts of patients with pulmonary tuberculosis in Turkey: a dispensary experience in 2016-2017. Trans R Soc Trop Med Hyg. 2019;113(6):351-5. [Crossref]  [PubMed] 

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