Evaluation of Osteoporosis Among Epileptic Patients on Monotherapy

Authors

  • Mufeed Akram Taha 1Department of Medicine, Assistant Professor of Neurology, College of Medicine, University of Kirkuk, Kirkuk, Iraq
  • Neven Nihal Hana Istifo Department of Pharmacology and Toxicology, College of Pharmacy, University of Kirkuk, Kirkuk, Iraq

DOI:

https://doi.org/10.31351/vol33iss1pp129-136

Keywords:

Epilepsy, Valproate, Carbamazepine, T- Score, Osteoporosis

Abstract

           Epilepsy is a common chronic neurological disorder that affects almost 50 million people worldwide. Most patients require long-term, and sometimes lifelong therapy with antiseizure medications (ASMs), our case control study evaluates the long-term effect of carbamazepine (CBZ) and valproate (VPA) on bone mineral density and bone health biochemical markers. 50 patients with newly diagnosed epilepsy who had no history of antiseizure medications (ASMs) intake prior were divided into 2 groups. In the first group, 25 patients started carbamazepine (CBZ) monotherapy, while the second group included 25 patients who started receiving valproate (VPA) monotherapy. Another 25 healthy individuals were considered as a control group. The primary outcome of our study is to evaluate the percentage of osteoporosis compared to the duration of ASM therapy measured by the T score at two different sites in the body at baseline, after 3 and 6 months of therapy, while measurements of bone biomarker variables are considered secondary outcomes. We found that CBZ and VPA significantly decreased the level of vitamin D3, Ca, P, the L3-L5, and right femoral neck T score with prolonged treatment duration, while the level of ALP increased with increasing duration of treatment in patients treated with CBZ but not in the VPA group. Furthermore, CBZ significantly decreased bone health biomarkers and T score before VPA and the control group, as well as there were no significant differences between the two sexes who received CBZ or VPA therapy on bone biomarkers. In conclusion, valproate will not affect bone biomarkers earlier, but with a longer duration of therapy, they may have the same effect as carbamazepine which requires the prescription of supportive vitamin D and Ca along with ASMs.

References

Fahmy EM, Rashed LA, Ismail RS, Helmy H, Mekkawy DA. Evaluation of bone health among epileptic patients using biochemical markers and DEXA scan: an Egyptian study. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery. 2018;54(1):1-8.

Dussault PM, Lazzari AA. Epilepsy and osteoporosis risk. Current Opinion in Endocrinology & Diabetes and Obesity. 2017;24(6):395-401.

AlKataan MAA, Mahmood AS, Al Mallakhdeer AS. Evaluation of the Detrimental Effects of some Antiepileptic Drugs on the Height and Weight of Children with Epilepsy. Iraqi Journal of Pharmaceutical Sciences (P-ISSN 1683-3597 E-ISSN 2521-3512). 2022;31(1):241-5.

Pitetzis DA, Spilioti MG, Yovos JG, Yavropoulou MP. The effect of VPA on bone: From clinical studies to cell cultures—The molecular mechanisms revisited. Seizure. 2017;48:36-43.

Yuluğ B, Özşimşek A, Öktem EÖ. Investigation of the Antiepileptics on Levels of Vitamin D and Calcium. Acta Medica Alanya. 2022;6(2):167-72.

Kumar D, Zafar L, Ashraf H, Ansari A. Alteration in bone metabolism and bone mineral density with chronic antiepileptic drug therapy. Apollo Medicine. 2022;19(4):213-8.

Zlibut A, Bocsan IC, Agoston-Coldea L. Pentraxin-3 and endothelial dysfunction. Advances in Clinical Chemistry. 2019;91:163-79.

AJMAL RS, SENGAR GS, KEERTI G. Effect of Ionic Calcium and Vitamin D3 in Lumbar Spine Bone Mineral Density of Paediatric Epileptic Patients on Antiepileptic Drugs. Journal of Clinical & Diagnostic Research. 2022;16(8).

Hamed SA. Influences of bone and mineral metabolism in epilepsy. Expert opinion on drug safety. 2011;10(2):265-80.

Yusupova D, Muratov Fk. Molecular mechanisms of influence antiepileptic therapy on mineral bone density in women of childbearing age with epilepsy. British Medical Journal. 2022;2(6).

Mishra S, Mishra D, Mahajan B, Mantan M, Khan AM. Effect of Daily Vitamin D Supplementation on Serum Vitamin D Levels in Children with Epilepsy Receiving Sodium Valproate Monotherapy: A Randomized, Controlled Trial. Indian Journal of Pediatrics. 2022.

Ashraf H, Zafar L, Kumar DA. Alteration in bone metabolism and bone mineral density with chronic anti-epileptic drug therapy in North Indian population. Indian Journal of Endocrinology and Metabolism. 2022;26(Suppl 1):S30.

Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, et al. The Recent Prevalence of Osteoporosis and Low Bone Mass in the United States Based on Bone Mineral Density at the Femoral Neck or Lumbar Spine. Journal of Bone and Mineral Research. 2014;29(11):2520-6.

Doroudinia A, Colletti PM. Bone mineral measurements. Clinical nuclear medicine. 2015;40(8):647-57.

Agency IAE. Dual Energy X Ray Absorptiometry for Bone Mineral Density and Body Composition Assessment: IAEA Human Health Series No. 15: International Atomic Energy Agency; 2011: 2-5

Saltik S, İşgüven P, Ergüven M, Dursun F, Özlü S. Karbamazepin ve valproik asit kullanan çocuklarda kemik metabolizmasının değerlendirilmesi. Epilepsi Dergisi. 2005;11(2):77-82.

Ecevit Ç, Aydoğan A, ülay Kavakli T, Altinöz S. Effect of carbamazepine and valproate on bone mineral density. Pediatric neurology. 2004;31(4):279-82.

Pack AM, Morrell MJ. Epilepsy and bone health in adults. Epilepsy & Behavior. 2004;5:24-9.

Andersen NB, Jørgensen NR. Impaired bone health as a co-morbidity of epilepsy. Best Practice & Research Clinical Rheumatology. 2022;36(3):101755.

Yürekli V, Akkuş S, Akhan G, Tamer MN, Yönden Z. Uzun süreli antiepileptik ilaç tedavisine bağlı osteomalazi. SDÜ Tıp Fakültesi Dergisi. 2005;12(2):34-7.

Barbella G, Barras P, Rossetti AO, Novy J. Hypophosphatemia compared to classical biomarkers of tonic clonic seizures. Epilepsy research. 2020;163:106326:1-5

van Kempen TA, Deixler E. SARS-CoV-2: influence of phosphate and magnesium, moderated by vitamin D, on energy (ATP) metabolism and on severity of COVID-19. American Journal of Physiology-Endocrinology and Metabolism. 2021;320(1):E2-E6.

Barras P, Siclari F, Hügli O, Rossetti AO, Lamy O, Novy J. A potential role of hypophosphatemia for diagnosing convulsive seizures: A case-control study. Epilepsia. 2019;60(8):1580-5.

Zhang X, Zhong R, Chen Q, Li M, Lin W, Cui L. Effect of carbamazepine on the bone health of people with epilepsy: a systematic review and meta-analysis. Journal of International Medical Research. 2020;48(3):2-9.

Dulkadir R, Gülerman HF, Bülbül SFH. Vitamin D deficiency in healthy adolescents aged 12–17 years in Kirikkale, Turkey: Vitamin D deficiency adolescents. Medical Science and Discovery. 2022;9(12):656-61.

Hodsman AB, Bauer DC, Dempster DW, Dian L, Hanley DA, Harris ST, et al. Parathyroid hormone and teriparatide for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use. Endocrine reviews. 2005;26(5):688-703.

van der Burgh AC, de Keyser CE, Zillikens MC, Stricker BH. The effects of osteoporotic and non-osteoporotic medications on fracture risk and bone mineral density. Drugs. 2021:1-28.

Aksoy A, Sönmez FM, Deger O, Hosver I, Karagüzel G. The effects of antiepileptic drugs on the relationships between leptin levels and bone turnover in prepubertal children with epilepsy. 2011;24(9-10):703-8.

Triantafyllou N, Lambrinoudaki I, Armeni E, Evangelopoulos E-M, Boufidou F, Antoniou A, et al. Effect of long-term valproate monotherapy on bone mineral density in adults with epilepsy. Journal of the neurological sciences. 2010;290(1-2):131-4.

Guo Y, Lin Z, Huang Y, Yu L. Effects of valproate, lamotrigine, and levetiracetam monotherapy on bone health in newly diagnosed adult patients with epilepsy. Epilepsy & Behavior. 2020;113:107489.

Griepp DW, Kim DJ, Ganz M, Dolphin EJ, Sotudeh N, Burekhovich SA, et al. The effects of antiepileptic drugs on bone health: A systematic review. Epilepsy Research. 2021;173:106619.

Pack AM, Olarte LS, Morrell MJ, Flaster E, Resor SR, Shane E. Bone mineral density in an outpatient population receiving enzyme-inducing antiepileptic drugs. Epilepsy & Behavior. 2003;4(2):169-74.

Broecker-Preuss M, Arzideh F, Best J, Canbay A, Özçürümez M, Manka P. Comparison of age-and sex-dependent reference limits derived from distinct sources for metabolic measurands in basic liver diagnostics. Zeitschrift für Gastroenterologie. 2023;61(01):50-9.

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Published

2024-03-29