Epilepsy, a chronic neurological disorder affecting millions globally, necessitates long-term pharmacotherapy with antiepileptic drugs (AEDs) [1, 7]. While effective in seizure control, AEDs are increasingly recognized for their systemic side effects, particularly their detrimental impact on bone health [2, 3, 4, 5, 6, 8, 9, 10]. This cross-sectional study aimed to investigate the relationship between antiepileptic medication use, calcium metabolism, and bone mineral density (BMD) in a cohort of adult patients with epilepsy. We assessed various biochemical markers of bone turnover and measured BMD at critical skeletal sites. Our findings suggest a significant association between AED exposure, particularly with enzyme-inducing AEDs and polypharmacy, and adverse alterations in calcium homeostasis and reduced BMD. These results underscore the importance of routine monitoring of bone health parameters in patients on long-term AED therapy to facilitate early intervention and mitigate the risk of debilitating bone complications.

Antiepileptic drugs, bone mineral density, calcium homeostasis

World Health Organization. Available from: https://www.who.int/news-room/fact-sheets/detail/epilepsy. [Last accessed on Dec 2023].

Carpay JA, Aldenkamp AP, van Donselaar CA. Complaints associated with the use of antiepileptic drugs: Results from a community-based study.10 Seizure 2005;14:198–206.

Sheth RD, Binkley N, Hermann BP. Progressive bone deficit in epilepsy. Neurology 2008;70:170–6.

Ensrud KE, Walczak TS, Blackwell T, Ensrud ER, Bowman PJ, Stone KL. Antiepileptic drug use increases rates of bone loss in older women: A prospective study.11 Neurology 2004;62:2051–7.12

Andress DL, Ozuna J, Tirschwell D, Grande L, Johnson M, Jacobson AF, et al. Antiepileptic drug-induced bone loss in young male patients who have seizures.13 Arch Neurol 2002;59:781–6.14

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;8:34–46.

Beghi E. The epidemiology of epilepsy. Neuroepidemiology 2020;54:185–91.

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;5:248–53.

Siniscalchi A, Murphy S, Cione E, Piro L, Sarro G, Gallelli L. Antiepileptic drugs and bone health: Current concepts.15 Psychopharmacol Bull 2020;50:36–44.

Farhat G, Yamout B, Mikati MA, Demirjian S, Sawaya R, El-Hajj Fuleihan G. Effect of antiepileptic drugs on bone density in ambulatory patients. Neurology 2002;58:1348–53.16

Ebrahim K, Legese N, Tadiwos Y, Tola A. Prevalence of anti-epileptic drugs polypharmacy and associated factors among epileptic patients in Hiwot Fana Specialized University Hospital, Harar, Ethiopia. Res Sq 2021;13:359.

Lee-Lane E, Torabi F, Lacey A, Fonferko-Shadrach B, Harris D, Akbari A, et al. Epilepsy, antiepileptic drugs, and the risk of major cardiovascular events. Epilepsia 2021;62:1604–16.

Salimipour H, Kazerooni S, Seyedabadi M, Nabipour I, Nemati R, Iranpour D, et al. Antiepileptic treatment is associated with bone loss: Difference in drug type and region of interest.17 J Nucl Med Technol 2013;41:208–11.

Bansal A, Shah S, Kumar S, Haldar A, B KM, Brahma S, et al. Demographic profile and prescribing patterns of anti-epileptic drugs in Indian epilepsy patients: Electronic medical record-based nation-wide retrospective cohort study. Cureus 2022;14:e23676.

Coralic Z, Kapur J, Olson KR, Chamberlain JM, Overbeek D, Silbergleit R. Treatment of toxin-related status epilepticus with levetiracetam, fosphenytoin, or valproate in patients enrolled in the Established Status Epilepticus Treatment Trial. Ann Emerg Med 2022;80:194–202.

Joshi R, Tripathi M, Gupta P, Gupta YK. Effect of clobazam as add-on antiepileptic drug in patients with epilepsy. Indian J Med Res 2014;140:209–15.

Contreras-García IJ, Cárdenas-Rodríguez N, Romo-Mancillas A, Bandala C, Zamudio SR, Gómez-Manzo S, et al. Levetiracetam mechanisms of action: From molecules to systems. Pharmaceuticals (Basel) 2022;15:475.

Lee JW, Dworetzky B. Rational polytherapy with antiepileptic drugs. Pharmaceuticals (Basel) 2010;3:2362–79.

Khan M, Jose A, Sharma S.. Physiology, Parathyroid Hormone. Treasure Island, FL: StatPearls Publishing.

Reimers A, Berg JA, Burns ML, Brodtkorb E, Johannessen SI, Johannessen Landmark C. Reference ranges for antiepileptic drugs revisited: A practical approach to establish national guidelines. Drug Des Devel Ther 2018;12:271–80.

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. Egypt J Neurol Psychiatr Neurosurg 2018;54:10.

Rajan GV, Sreenivasaiah B, Lunavath N, Yerroju K. Effect of antiepileptic drugs on bone metabolism in children using biochemical markers: A case control study. Int J Contemp Pediatr 2023;10:1100–7.

Hasaneen B, Elsayed RM, Salem N, Elsharkawy A, Tharwat N, Fathy K, et al. Bone mineral status in children with epilepsy: Biochemical and radiologic markers. J Pediatr Neurosci 2017;12:138–43.

Rauchenzauner M, Griesmacher A, Tatarczyk T, Haberlandt E, Strasak A, Zimmerhackl LB, et al. Chronic antiepileptic monotherapy, bone metabolism, and body composition in non‐institutionalized children. Dev Med Child Neurol 2010;52:283–8.

Bouillon R, Reynaert J, Claes JH, Lissens W, De Moor P. The effect of anticonvulsant therapy on serum levels of 25-hydroxy-vitamin D, calcium, and parathyroid hormone. J Clin Endocrinol Metab 1975;41:1130–5.

Meier C, Kraenzlin ME. Antiepileptics and bone health. Ther Adv Musculoskelet Dis 2011;3:235–43.