.: ORİJİNAL ARAŞTIRMA
The Effect of Antiepileptic Drug Therapy on Bone Metabolism and its Relationship with Vitamin D Receptor Gene
Antiepileptik İlaç Tedavisinin Kemik Metabolizması Üzerine Etkisi ve D Vitamini Reseptör Geni ile İlişkisi
Turkiye Klinikleri J Pediatr. 2019;28(3):121-7
doi: 10.5336/pediatr.2019-70621
Makale Dili: EN
Tam Metin
Ücretsiz Erişim
ABSTRACT
Objective: The relationship between antiepileptic drugs and bone health and also the genetic aspect of this relationship is not clear and has been investigated in recent years. The aim of this study was to determine the effects of different antiepileptic drugs (AEDs) on bone mineral density results in long term follow up and to evaluate the relationship with the vitamin D profile (Bsml mutation) of the patients. Material and Methods: Eighty ambulatory patients (21 male, 59 female; mean age: 9.1±3.85 years) were included in the study. The patients were divided into four groups; Group 1 (levetiracetam), Group 2 (Carbamazepine), Group 3 (Valproic acid) and Group 4 (control). The plasma calcium, phosphorus, parathyroid hormone, alkaline phosphatase, vitamin D levels and bone mineral density values of femur and spine (L1-4) were compared. The patients were divided into two groups according to vitamin D receptor genes as the patients with Bsml mutations and without (wild type) Bsml mutations. Results: The difference between bone mineral density, Z score, phosphorus, parathyroid hormone, alkaline phosphatase and vitamin D levels of the patients in all four groups was not statistically significant. The phosphorus, parathyroid hormone, alkaline phosphatase and vitamin D levels and bone mineral density and Z score results of the patients with and without Bsml mutations were not significantly different. Conclusion: In this cross-sectional analysis, we found that the bone mineral status of the patients receiving different AEDs for a long time (> 2 years) was not significantly different. There was also no loss of bone mineral content in the patient group when compared with age-appropriate controls. According to the results of this study, Bsml polymorphism is not determinant in the progression of bone mineral loss.
Keywords: Antiepileptic drug; bone mineral density; epilepsy
Objective: The relationship between antiepileptic drugs and bone health and also the genetic aspect of this relationship is not clear and has been investigated in recent years. The aim of this study was to determine the effects of different antiepileptic drugs (AEDs) on bone mineral density results in long term follow up and to evaluate the relationship with the vitamin D profile (Bsml mutation) of the patients. Material and Methods: Eighty ambulatory patients (21 male, 59 female; mean age: 9.1±3.85 years) were included in the study. The patients were divided into four groups; Group 1 (levetiracetam), Group 2 (Carbamazepine), Group 3 (Valproic acid) and Group 4 (control). The plasma calcium, phosphorus, parathyroid hormone, alkaline phosphatase, vitamin D levels and bone mineral density values of femur and spine (L1-4) were compared. The patients were divided into two groups according to vitamin D receptor genes as the patients with Bsml mutations and without (wild type) Bsml mutations. Results: The difference between bone mineral density, Z score, phosphorus, parathyroid hormone, alkaline phosphatase and vitamin D levels of the patients in all four groups was not statistically significant. The phosphorus, parathyroid hormone, alkaline phosphatase and vitamin D levels and bone mineral density and Z score results of the patients with and without Bsml mutations were not significantly different. Conclusion: In this cross-sectional analysis, we found that the bone mineral status of the patients receiving different AEDs for a long time (> 2 years) was not significantly different. There was also no loss of bone mineral content in the patient group when compared with age-appropriate controls. According to the results of this study, Bsml polymorphism is not determinant in the progression of bone mineral loss.
Keywords: Antiepileptic drug; bone mineral density; epilepsy
ÖZET
Amaç: Antiepileptik ilaçlar ile kemik sağlığı arasındaki ilişki, ayrıca bu ilişkinin genetik yönü net değildir ve son yıllarda araştırılmıştır. Bu çalışmanın amacı, farklı antiepileptik ilaçların uzun süreli takiplerde kemik mineral yoğunluğu sonuçları üzerine etkilerini belirlemek ve hastaların D vitamini profili (Bsml mutasyonu) ile ilişkilerini değerlendirmektir. Gereç ve Yöntemler: Çalışmaya 80 gezici hasta (21 erkek, 59 kız; yaş ort: 9,1±3,85 yıl) dahil edildi. Hastalar dört gruba ayrıldı; Grup 1 (Levetirasetam), Grup 2 (Karbamazepin), Grup 3 (Valproik asit) ve Grup 4 (kontrol). Plazma kalsiyum, fosfor, paratiroid hormonu, alkalen fosfataz, D vitamini düzeyleri ve femur ve vertebra (L1-4) kemik mineral yoğunluğu değerleri karşılaştırıldı. Hastalar D vitamin reseptörü genlerine göre Bsml mutasyonu olan ve (vahşi tip) Bsml mutasyonu olmayan olarak iki gruba ayrıldı. Bulgular: Dört grubun hepsinde kemik mineral yoğunluğu, Z skoru, fosfor, paratiroid hormonu, alkalen fosfataz ve D vitamini düzeyleri arasındaki fark istatistiksel olarak anlamlı değildi. Bsml mutasyonu olan ve olmayan hastaların fosfor, paratiroid hormonu, alkalen fosfataz, D vitamini düzeyleri ve kemik mineral yoğunluğu ve Z skorları arasında anlamlı fark yoktu. Sonuç: Bu kesitsel analizde, farklı antiepileptik ilaçları uzun süreli (>2 yıl) alan hastaların kemik mineral durumunun önemli ölçüde farklı olmadığını saptadık. Ayrıca yaşa uygun kontrol grubu ile kıyaslandığında hasta grubunda kemik mineral içeriği kaybı yoktu. Bu çalışmanın sonuçlarına göre Bsml polimorfizmi, kemik mineral kaybının ilerlemesinde belirleyici değildir.
Anahtar Kelimeler: Antiepileptik ilaç; kemik mineral yoğunluğu; epilepsi
Amaç: Antiepileptik ilaçlar ile kemik sağlığı arasındaki ilişki, ayrıca bu ilişkinin genetik yönü net değildir ve son yıllarda araştırılmıştır. Bu çalışmanın amacı, farklı antiepileptik ilaçların uzun süreli takiplerde kemik mineral yoğunluğu sonuçları üzerine etkilerini belirlemek ve hastaların D vitamini profili (Bsml mutasyonu) ile ilişkilerini değerlendirmektir. Gereç ve Yöntemler: Çalışmaya 80 gezici hasta (21 erkek, 59 kız; yaş ort: 9,1±3,85 yıl) dahil edildi. Hastalar dört gruba ayrıldı; Grup 1 (Levetirasetam), Grup 2 (Karbamazepin), Grup 3 (Valproik asit) ve Grup 4 (kontrol). Plazma kalsiyum, fosfor, paratiroid hormonu, alkalen fosfataz, D vitamini düzeyleri ve femur ve vertebra (L1-4) kemik mineral yoğunluğu değerleri karşılaştırıldı. Hastalar D vitamin reseptörü genlerine göre Bsml mutasyonu olan ve (vahşi tip) Bsml mutasyonu olmayan olarak iki gruba ayrıldı. Bulgular: Dört grubun hepsinde kemik mineral yoğunluğu, Z skoru, fosfor, paratiroid hormonu, alkalen fosfataz ve D vitamini düzeyleri arasındaki fark istatistiksel olarak anlamlı değildi. Bsml mutasyonu olan ve olmayan hastaların fosfor, paratiroid hormonu, alkalen fosfataz, D vitamini düzeyleri ve kemik mineral yoğunluğu ve Z skorları arasında anlamlı fark yoktu. Sonuç: Bu kesitsel analizde, farklı antiepileptik ilaçları uzun süreli (>2 yıl) alan hastaların kemik mineral durumunun önemli ölçüde farklı olmadığını saptadık. Ayrıca yaşa uygun kontrol grubu ile kıyaslandığında hasta grubunda kemik mineral içeriği kaybı yoktu. Bu çalışmanın sonuçlarına göre Bsml polimorfizmi, kemik mineral kaybının ilerlemesinde belirleyici değildir.
Anahtar Kelimeler: Antiepileptik ilaç; kemik mineral yoğunluğu; epilepsi
REFERANSLAR:
- Sander JW. The epidemiology of epilepsy revisited. Curr Opin Neurol. 2003;16(2):165-70. [Crossref] [PubMed]
- Souverein PC, Webb DJ, Petri H, Weil J, Van Staa TP, Egberts T. Incidence of fractures among epilepsy patients: a population-based retrospective cohort study in the General Practice Research Database. Epilepsia. 2005; 46(2):304-10. [Crossref] [PubMed]
- Hamed SA, Moussa EM, Youssef AH, Abd ElHameed MA, NasrEldin E. Bone status in patients with epilepsy: relationship to markers of bone remodeling. Front Neurol. 2014;5:142. [Crossref] [PubMed] [PMC]
- Yaghini O, Tonekaboni SH, Amir Shahkarami SM, Ahmad Abadi F, Shariat F, Abdollah Gorji F. Bone mineral density in ambulatory children with epilepsy. Indian J Pediatr. 2015;82(3):225-9. [Crossref] [PubMed]
- Koshy G, Varghese RT, Naik D, Asha HS, Thomas N, Seshadri MS, et al. Derangements in bone mineral parameters and bone mineral density in south Indian subjects on antiepileptic medications. Ann Indian Acad Neurol. 2014;17(3):272-6. [Crossref] [PubMed] [PMC]
- Krishnamoorthy G, Nair R, Sundar U, Kini P, Shrivastava M. Early predisposition to osteomalacia in Indian adults on phenytoin or valproate monotherapy and effective prophylaxis by simultaneous supplementation with calcium and 25-hydroxy vitamin D at recommended daily allowance dosage: a prospective study. Neurol India. 2010;58(2):213-9. [Crossref] [PubMed]
- Hamed SA. Influences of bone and mineral metabolism in epilepsy. Expert Opin Drug Saf. 2011;10(2):265-80. [Crossref] [PubMed]
- Boluk A, Guzelipek M, Savli H, Temel I, Ozisik HI, Kaygusuz A. The effect of valproate on bone mineral density in adult epileptic patients. Pharmacol Res. 2004;50(1):93-7. [Crossref] [PubMed]
- Beniczky SA, Viken J, Jensen LT, Andersen NB. Bone mineral density in adult patients treated with various antiepileptic drugs. Seizure. 2012;21(6):471-2. [Crossref] [PubMed]
- Serin HM, Koc ZP, Temelli B, Esen I. The bone mineral content alterations in pediatric patients medicated with levetiracetam, valproic acid, and carbamazepine. Epilepsy Behav. 2015;51:221-4. [Crossref] [PubMed]
- Phabphal K, Geater A, Limapichat K, Sathirapanya P, Setthawatcharawanich S, Leelawattana R. Effect of switching hepatic enzyme-inducer antiepileptic drug to levetiracetam on bone mineral density, 25 hydroxyvitamin D, and parathyroid hormone in young adult patients with epilepsy. Epilepsia. 2013;54(6):e94-8. [Crossref] [PubMed]
- Lazzari AA, Dussault PM, Thakore-James M, Gagnon D, Baker E, Davis SA, et al. Prevention of bone loss and vertebral fractures in patients with chronic epilepsy--antiepileptic drug and osteoporosis prevention trial. Epilepsia. 2013;54(11):1997-2004. [Crossref] [PubMed]
- Lambrinoudaki I, Kaparos G, Armeni E, Alexandrou A, Damaskos C, Logothetis E, et al. BsmI vitamin D receptor's polymorphism and bone mineral density in men and premenopausal women on long-term antiepileptic therapy. Eur J Neurol. 2011;18(1):93-8. [Crossref] [PubMed]
- Pack AM. Genetic variation may clarify the relationship between epilepsy, antiepileptic drugs, and bone health. Eur J Neurol. 2011;18(1):3-4. [Crossref] [PubMed]
- Thakkinstian A, D'Este C, Eisman J, Nguyen T, Attia J. Meta-analysis of molecular association studies: vitamin D receptor gene polymorphisms and BMD as a case study. J Bone Miner Res. 2004;19(3):419-28. [Crossref] [PubMed]
- Uitterlinden AG, Burger H, Huang Q, Yue F, McGuigan FE, Grant SF, et al. Relation of alleles of the collagen type Ialpha1 gene to bone density and the risk of osteoporotic fractures in postmenopausal women. N Engl J Med. 1998;338(15):1016-21. [Crossref] [PubMed]
- Villegas-Martinez I, de-Miguel-Elizaga I, Carrasco-Torres R, Marras C, Canteras-Jordana M, Yedra-Guzman MJ, et al. The COL1A1 SP1 polymorphism is associated with lower bone mineral density in patients treated with valproic acid. Pharmacogenet Genomics. 2016;26(3):126-32. [Crossref] [PubMed]
- Anderson GD. Pharmacogenetics and enzyme induction/inhibition properties of antiepileptic drugs. Neurology. 2004;63(10 Suppl 4):S3-8. [Crossref] [PubMed]
- Phabphal K, Geater A, Limapichat K, Sathirapanya P, Setthawatcharawanich S, Leelawattana R. The association between CYP 2C9 polymorphism and bone health. Seizure. 2013;22(9):766-71. [Crossref] [PubMed]
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