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Background: Vitamin D is essential for bone physical condition, and vitamin D insufficiency may add to further autoimmune diseases, infections or even cancer. Enzyme-inducing antiepileptic drugs have been predominantly linked with osteoporosis hazard proved their impacts on vitamin D. The study aim was to determine the prevalence of vitamin D insufficiency and deficiency and the covariates associated with it among the adult epileptic patients attending King Fahd neurology outpatient clinics.
Subjects and Methods: 297 adult epilepsy patients joined this cross-sectional study at King Fahd Hospital in 2017. Vitamin D level was considered as deficiency (<10ng/ml), insufficiency (<30ng/ml), or normal (≥30ng/ml). Antiepileptic drugs were sorted out according to their enzyme inducing criteria.
Results: 87.88% adult epileptic patients were between 18 – 50 years of age, more than half were females, married, and with higher degree of education, less than half received monthly income of less than 5,000 SR, nearly two third were either smokers or ex-smokers. Multiple linear regression model for predictors of vitamin D insufficiency and deficiency declared that; enzyme induced antiepileptic drugs, polytherapy, and smoking were significantly correlated with vitamin deficiency and insufficiency (p < 0.05).
Conclusion: Vitamin D insufficiency and deficiency is widespread among adult epileptic patients. Screening of vitamin D level should be taken into consideration as part of the regular follow up of epileptic patients.
Rosen CJ, Adams JS, Bikle DD, et al. The nonskeletal effects of vitamin D: an Endocrine Society scientific statement. Endocr Rev. 2012;33(3):456–92.
Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96:1911–30.
Ganji V, Zhang X, Tangpricha V. Serum 25-hydroxyvitamin D concentrations and prevalence estimates of hypovitaminosis D in the U.S. population based on assay-adjusted data. J Nutr. 2012;142(3):498–507.
Lee RH, Lyles KW, Colón-Emeric C. A review of the effect of anticonvulsant medications on bone mineral density and fracture risk. Am J Geriatr Pharmacother. 2010;8(1):34–46.
Vestergaard P. Epilepsy, osteoporosis and fracture risk - a meta-analysis. Acta Neurol Scand. 2005;112(5):277–86.
Pack AM, Morrell MJ, Randall A, McMahon DJ, Shane E. Bone health in young women with epilepsy after one year of antiepileptic drug monotherapy. Neurology. 2008;70(18):1586–93.
Robien K, Oppeneer SJ, Kelly JA, Hamilton-Reeves JM. Drug-vitamin D interactions: a systematic review of the literature. Nutr Clin Pract. 2013;28(2):194–208.
WHO | Epilepsy. WHO. Available: http://www.who.int/mediacentre/factsheets/fs999/en/
Sander, J. W. The Use of Antiepileptic Drugs—Principles and Practice. Epilepsia. 2004;45:28–34.
Pugliatti M, Beghi E, Forsgren L, Ekman M, Sobocki P. Estimating the Cost of Epilepsy in Europe: A Review with Economic Modeling. Epilepsia. 2007;48:2224–2233.
Halpern M, Rentz A, Murray M. Cost of illness of epilepsy in the US: comparison of patient-based and population-based estimates. Neuroepidemiology. 2000;19:87–99.
U.S. Census Bureau. US Census Bureau, Census Interactive Population Map; 2010. Available: https://www.census.gov/2010census/popmap/.
Kumar et al., 2009: Kumar J, Muntner P, Kaskel FJ, Hailpern SM, Melamed ML. Prevalence and associations of 25-hydroxyvitamin D deficiency in US children: NHANES 2001–2004. Pediatrics. 2009;124(3):e362–70.
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;54:1997–2004.
Jaydip Ray, Kandadi Rukmini, Chakarta Rathnakishore, Banda Balarajj, Siriniyasargo Bandaru. Association of 25-Hydroxyvitamin D Deficiency in Epileptic Patients.Iran J Child Neurol. 2017;11(2):48-56.
Ogden OL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011–2012. JAMA. 2014;311(8):806–14.
Menon B, Harinarayan CV. The effect of anti epileptic drug therapy on serum 25-hydroxyvitamin D and parameters of calcium and bone metabolism a longitudinal study. Seizure. 2010;19:153–58.
Gniatkowska-Nowakowska A. Fractures in epilepsy children. Seizure. 2010;19:324–25.
Shellhaas RA, Barks AK, Joshi SM. Prevalence and risk factors for vitamin D insufficiency among children with epilepsy. Pediatr Neurol. 2010;42:422–26.
Nettekoven S, Strohle A, Trunz B, Wolters M, Hoffmann S, Horn R, et al. Lichtinghagen R, Welkoborsky HJ, Tuxhorn I, Hahn A. Effects of antiepileptic drug therapy on vitamin D status and biochemical markers of bone turnover in children with epilepsy. Eur J Pediatr. 2008;167:1369–77.
Pack AM, Morrell MJ, McMahon DJ, Shane E. Normal vitamin D and low free estradiol levels in women on enzyme-inducing antiepileptic drugs. Epilepsy Behav. 2011a;21(4):453–8.
Mikati MA, Dib L, Yamout B, Sawaya R, Rahi AC, Fuleihan GE. Two randomized vitamin D trials in ambulatory patients on anticonvulsants: impact on bone. Neurology. 2006;67(11):2005–14.
Holló A, Clemens Z, Lakatos P. Epilepsy and vitamin D. Int J Neurosci. 2014;124(6):387–93.
Herman ST. Screening bone mineral density in epilepsy: A call to action, but what action? Epi Curr. 2009;9(2):44–6.
Babayigit A, Dirik E, Bober E, Cakmakci H. Adverse effects of antiepileptic drugs on bone mineral density. Pediatr Neurol. 2006;35:177–81.
Pack AM. The impact of long-term antiepileptic drug use on bone health. Advanced Students. 2005;5:S567–71.
Voudris KA, Attilakos A, Katsarou E, Garoufi A, Dimou S, Skardoutsou A, et al. Early alteration in bone metabolism in epileptic children receiving carbamazepine monotherapy owing to the induction of hepatic drug-metabolizing enzymes. J Child Neurol. 2005;20:513–16.
Krishnamoorthy G, Karande S, Ahire N, Mathew L, Kulkarni M. Bone Metabolism Alteration on Antiepileptic Drug Therapy. Indian J Pediatr. 2009;76:377–83.
Nakken KO, Taubøll E. Bone loss associated with use of antiepileptic drugs. Expert Opin. Drug Saf. 2010;9:561–571.
Teagarden DL, Meador KJ, Loring DW. Low vitamin D levels are common in patients with epilepsy. Epilepsy Res. 2014;108:1352–56.
Misra A, Aggarwal A, Singh O, Sharma S. Effect of carbamazepine therapy on vitamin D and parathormone in epileptic children. Pediatr Neurol. 2010 Nov;43:320–24.
MintzerS , Boppana P, Toguri J, DeSantis A. Vitamin D levels and bone turnover in epilepsy patients taking carbamazepine or oxcarbamazepine. Epilepsia. 2006;47:510–15.
Pack AM, Morrell MJ. Adverse effect of antiepileptic drug on bone structure: Epidemiology mechanisms and therapeutic indications. CNS Drugs. 2001;15:633–42.
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;82:225–29.
Verrotti A, Greco R, Morgese G, Chiarelli F. Increased bone turnover in epileptic patients treated with carbamazepine. Ann Neurol. 2000;47:385–88.
Ginige N, de Silva KSH, Wanigasinghe JK, Gunawardane NS, Munasinghe TMJ. Effects of long term anti epileptic drugs on serum vitamin D levels and bone profile in a cohort of Sri Lankan children. Int J Pediatr Endocrinol. 2015;2015(Suppl 1):66.
Farhat G. et al. Effect of antiepileptic drugs on bone density in ambulatory patients. Neurology. 2002;58:1348–1353.
Cansu A, Yesilkaya E, Serdaroglu A, Hirfanoglu TL, Camurdan O, Gulbahar O, et al. Evaluation of bone turnover in epileptic children using oxcarbazepine. Pediatr Neurol. 2008;39:266–71.
Bergqvist AG, Schall JI, Stallings VA. Vitamin D status in children with intractable epilepsy, and impact of the ketogenic diet. Epilepsia. 2007;48:66–71.
Nicolaidou P, Georgouli H, Kotsalis H, Matsinos Y, Papadopoulou A, Fretzayas A, et al. Effects of anticonvulsant therapy on vitamin D status in children: Prospective monitoring study. J Child Neurol. 2006;21:205–09.
Hosseinpour F, Ellfolk M, Norlin M, Wikvall K. Phenobarbital suppresses vitamin D3 25-hydroxylase expression: a potential new mechanism for drug-induced osteomalacia. Biochem Biophys Res Commun. 2007;357:603–07.
Heo K, Rhee Y, Lee HW, Lee SA, Shin DJ, Kim WJ, 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;52:1884–89.
Pack AM. The association between antiepileptic drugs and bone disease. Epilepsy Curr. 2003;3:91–95.
Razazizan N, Mirmoeini M, Daeichin S, Ghadiri K. Comparison of 25-hydroxy vitamin D, calcium and alkaline phosphatase levels in epileptic and non-epileptic children. Acta Neurol Taiwan. 2013;22:112–16.
Bianchini G, Mazzaferro S, Mancini U, Bianchi AR, Donato G, Massimetti C, et al. Calcium phosphorus changes in chronic anticonvulsant therapy: effects of administration of 25 hydroxy vitamin D3 on secondary hyperparathyroidism. Acta Vitaminol Enzymol. 1983;5:229–34.
Drezner MK. Treatment of anticonvulsant drug – induced bone disease. Epilepsy Behav. 2004;5:S41–7.
Howard JM. Anticonvulsant induced bone disease Editorial. Arch Neurol. 2004;58:1352–53.