Prognosticators of bone health in pediatrics with epilepsy using anti-epileptic drugs

A prospective interventional study

https://doi.org/10.53730/ijhs.v6nS10.13735

Authors

  • G. J. K. Prakash Raju Ph.D. scholar, Department of Pharmacology , Saveetha Medical College and Hospital, Chennai, Tamilnadu, India
  • Kannan Rajendran Professor, Department of Medicine, Saveetha Medical College and Hospital, Chennai, Tamilnadu, India
  • Dwajani S. Associate Professor, Department of Pharmacology, Senior Research Associate, Central Research laboratory, Rajarajeswari Medical College and Hospital, Bengaluru, Karnataka, India
  • Adarsh E. Professor, Department of Pediatrics, Rajarajeswari Medical College and Hospital, Bengaluru, Karnataka, India
  • A. S. Paveena Department of studies in statistics, University of Mysore, Manasagangotri, Mysore

Keywords:

bone biomarkers, bone health, carbamazepine, levetiracetam, monotherapy, pediatrics with epilepsy, sodium valproate

Abstract

Introduction: Epilepsy is a common and long-lasting neurological disorder in children who require long-term treatment with Antiepileptic drugs (AED). Such long-term AED use may have negative effects on bone causing bone loss and osteoporosis, necessitating frequent monitoring. Data on the effect of AED on bone health in children is scarce compared to adults and hence this study was undertaken.  Aim: To compare and quantify the effects of sodium valproate (SV), carbamazepine (CBZ), and levetiracetam (LEV) on bone health in children using specific bone biomarkers such as vitamin D, calcium, phosphorus, ALP, osteocalcin (OCN), and beta serum cross laps (CTx). Materials and methods: A prospective interventional study was carried out in Rajarajeswari Medical College and Hospital, Bangalore, between October 2019 to March 2022. A total of 79 confirmed cases of epilepsy within the age group of 1-18 years, receiving treatment with sodium valproate (SV), carbamazepine (CBZ), and levetiracetam (LEV) monotherapy for a period of minimum one month were enrolled. Serum samples of calcium (Ca), phosphorus (PO4), alkaline phosphatase (ALP), Vitamin D were analyzed at the time of initiation of study and these levels were considered as baseline levels. 

Downloads

Download data is not yet available.

References

Aksoy A, Sonmez FM, Deger O, Hosver I, Karaguzel G. The effects of antiepileptic drugs on the relationships between leptin levels and bone turnover in prepubertal children with epilepsy. J Pediatr Endocrinol Metab. 2011;24(9 –10):703 –8.

Arora E, Singh H, Gupta YK. Impact of antiepileptic drugs on bone health: Need for monitoring, treatment, and prevention strategies. J Family Med Prim Care. 2016 Apr-Jun;5(2):248-253.

Ashrafi M, Khoshhal F, Rabani A, Salajegheh N, Nasab AM, Shams S, et al. Study of Antiepileptic Drugs effects on bone metabolism. Iranian Journal of Pediatrics. 2005; 15(4):347-52.

Barden HS, Mazess RB, Chesney RW, et al: Bone status of children receiving anticonvulsant therapy. Metab Bone Dis Relat Res 1982; 4:43–47.

C. Meier, M.E. Kraenzlin. Antiepileptics and bone health. Adv Musculoskelet Dis, 3 (5) (2011): 235-243

Caksen H, Dulger H, Cesur Y, Odabas D, Tuncer O, Atas B. No effect of long-term valproate therapy on thyroid and parathyroid functions in children. Int J Neurosci. 2002;112(11):1371 –4.

Chaokromthong K, Sintao N. Sample Size Estimation using Yamane and Cochran and Krejcie and Morgan and Green Formulas and Cohen Statistical Power Analysis by G* Power and Comparisions. Apheit International Journal. 2021 Dec 24;10(2):76-86.

de Melo VC, Ferreira PR, Ricardi LO, Batista MC, França CN, Ferreira CE. Definition of reference ranges for β-isomerized carboxy-terminal telopeptide collagen type I for children and adolescents. Journal of Pediatric Endocrinology and Metabolism. 2018 Jun 1;31(6):637-40.

Dwajani S, et al. Effect of Sodium Valproate and Levetiracetam on Thyroid Hormones in Pediatric Patients with Epilepsy. Adv in Phar & Clin Tria 2020, 5(3): 000182

Dwajani S., GRK Sarma, Ganapathy Bantwal, Chanda Kulkarni. Effects Of Levetiracetam And Topiramate On Bone Health In Adults, Using Bone Specific Biomarkers. Med. Res. Chron., 2015, 2 (1), 61-66.

Erbayat Altay E, Serdaroglu A, Tumer L, Gucuyener K, Hasanoglu AJ. Evaluation of bone mineral metabolism in children receiving carbamazepine and valproic acid. J. Pedzziatr. Endocrinol. Metab. 2000; 13: 933–9.

Hamed SA, Moussa EMM, Youssef AH, Abd ElHameed MA, NasrEldin E. Bone status in patients with epilepsy: relationship to markers of bone remodeling. Front Neurol. 2014;5(August):142.

Hirokazu Tsukahara, Kouki Kimura, Yukiko Todoroki, Yusei Ohshima, Masahiro Hiraoka, Yosuke Shigematsu, Yasuyo Tsukahara, Masakazu Miura And Mitsufumi Mayumi. Bone mineral status in ambulatory pediatric patients on long-term anti-epileptic drug therapy. Pediatrics International (2002) 44, 247–253

Koo DL, Joo EY, Kim D, Hong SB. Effects of levetiracetam as a monotherapy on bone mineral density and biochemical markers of bone metabolism in patients with epilepsy. Epilepsy Res. 2013 Mar;104(1-2):134-9.

Kumar G, Dash P, Patnaik J, Pany G. Socioeconomic status scale-modified kuppuswamy scale for the year 2022. International Journal of Community Dentistry. 2022 Jun 10;10(1):1-6.

Min L, Chunyan W, Biaoxue R. Effects of valproic acid on skeletal metabolism in children with epilepsy: a systematic evaluation and meta-analysis based on 14 studies. BMC Pediatr. 2020 Mar 2;20(1):97.

Monjardino T, Silva P, Amaro J, Carvalho O, Guimaraes JT, Santos AC, Lucas R. Bone formation and resorption markers at 7 years of age: Relations with growth and bone mineralization. PloS one. 2019 Aug 22;14(8):e0219423

Morgan, Sarah L, and Ginnie L Prater. “Quality in dual-energy X-ray absorptiometry scans.” Bone vol. 104 (2017): 13-28.

Nakhaeymoghadam M, Teimouri A, Khaje A, hoseini SB. Bone Metabolism Disorder in Epileptic Children. Iran J Child Neurol. Spring 2018; 12(2): 17-24

Oner N, Kaya M, Karasalihoglu S, Karaca H, Celtik C, Tutunculer F. Bone mineral metabolism changes in epileptic children receiving valproic acid. J Paediatr Child Health. 2004;40(8):470 –3.

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

Peichl P, Griesmacherb A, Marteau R. et al. Serum cross laps in comparison to serum osteocalcin and urinary bone resorption markers. Clinical Biochemistry 2001; 34:131-9.

Petty SJ, O’Brien T, Wark J. Anti-epileptic medication and bone health. Osteoporosis international.2007; 18(2):129-42.

Razazizan, Nazanin et al. “Comparison of 25-hydroxy vitamin D, calcium and alkaline phosphatase levels in epileptic and non-epileptic children.” Acta neurologica Taiwanica vol. 22,3 (2013): 112-6.

Rifai Nader et al. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Elsevier 2018.Reference information for clinical laboratory:2258-302

Sato Y, Kondo I, Ishida S, Motooka H, Takayama K, Tomita Y, et al. Decreased bone mass and increased bone turnover with valproate therapy in adults with epilepsy [RETRACTED]. Neurology. 2001 Aug 14;57(3):445.

Serin HM, Koç ZP, Temelli B, Esen İ. The bone mineral content alterations in pediatric patients medicated with levetiracetam, valproic acid, and carbamazepine. Epilepsy & Behavior. 2015 Oct 1;51:221-4.

Seydewitz H, Henschen M, Kühnel W, Brandis M. Pediatric Reference Ranges for Osteocalcin Measured by the Immulite Analyzer. 2001;39(10): 980-82.

Shi K-L, Guo J-X, Zhao H-M, Hong H, Yang C-Z, Wu Y-H, et al. The effect of levetiracetam and oxcarbazepine monotherapy on thyroid hormones and bone metabolism in children with epilepsy: A prospective study. Epilepsy Behav [Internet]. 2020;113(107555):107555.

Suljic EM, Mehicevic A, Mahmutbegovic N. Effect of Long-term Carbamazepine Therapy on Bone Health. Med Arch. 2018 Oct;72(4):262-266.

Takeshita N, Seino Y, Ishida H et al. Increased circulating levels of γ-carboxyglutamic acid containing protein and decreased bone mass in children on anticonvulsant therapy. Calcif. Tissue Int. 1989; 44: 80–5.

Tatum, W O 4th et al. “The neurosurgical treatment of epilepsy.” Archives of family medicine vol. 9,10 (2000): 1142-7.

Tripathi, K. D. Essentials of Medical Pharmacology. 8th ed., Jaypee Brothers Medical, 2018.Antiepileptic drugs :444-445

Tripathi, K. D. Essentials of Medical Pharmacology. 8th ed., Jaypee Brothers Medical, 2018.Antiepileptic drugs :442-47

Verrotti A, Agostinelli S, Coppola G, Parisi P, Chiarelli F. A 12-month longitudinal study of calcium metabolism and bone turnover during valproate monotherapy. Eur J Neurol. 2010 Feb;17(2):232-7.

Verrotti A, Coppola G, Parisi P, Mohn A, Chiarelli F. Bone and calcium metabolism and antiepileptic drugs. Clinical neurology and neurosurgery. 2010;112(1):1-10.

Yang L, Grey V. Pediatric reference intervals for bone markers. Clinical biochemistry. 2006 Jun 1;39(6):561-8.

Zhang Y, Zheng YX, Zhu JM, Zhang JM, Zheng Z. Effects of antiepileptic drugs on bone mineral density and bone metabolism in children: A meta-analysis. J Zhejiang Univ Sci B. 2015;16(7):611–21. 5.

Published

08-12-2022

How to Cite

Raju, G. J. K. P., Rajendran, K., Dwajani, S., Adarsh, E., & Paveena, A. S. (2022). Prognosticators of bone health in pediatrics with epilepsy using anti-epileptic drugs: A prospective interventional study. International Journal of Health Sciences, 6(S10), 918–929. https://doi.org/10.53730/ijhs.v6nS10.13735

Issue

Section

Peer Review Articles