Skip to main content
Top
Published in: Current Treatment Options in Neurology 4/2011

01-08-2011 | Epilepsy

Treatment of Epilepsy to Optimize Bone Health

Author: Alison M. Pack, MD, MPH

Published in: Current Treatment Options in Neurology | Issue 4/2011

Login to get access

Opinion statement

When treating a person with epilepsy, one must consider many factors in addition to the obvious need to treat the seizures. Both epilepsy itself and treatment with antiepileptic drugs (AEDs) subject one to numerous potential secondary long-term health concerns. Poor bone health is one of these concerns. Studies suggest that persons with epilepsy treated with AEDs have an increased risk of fracture, low bone mineral density (BMD), and abnormalities in bone metabolism. Multiple factors likely contribute to the increased risk. Falls during generalized tonic-clonic seizures, secondary effects of AEDs on balance, inactivity, low BMD, reduced calcium intake, reduced active vitamin D metabolites, and a genetic predisposition to low BMD may all contribute. Studies suggest a differential influence of AEDs. Phenytoin, phenobarbital, and primidone are most consistently associated with a negative impact on bone. Carbamazepine and valproate may also result in bone abnormalities, but data are mixed. Current studies suggest that lamotrigine has limited (if any) effect, but again, data are inconsistent. Other AEDs have received limited study. Screening for poor bone health includes serologic testing of vitamin D metabolites (notably 25-hydroxyvitamin D) as well as BMD testing using dual energy x-ray absorptiometry. Optimizing intake of calcium and vitamin D is important for all persons with epilepsy treated with AEDs. Although many treatments for low BMD are available, these agents have not been studied in persons with epilepsy treated with AEDs. Overall, physicians treating persons with epilepsy must consider the potential effect of having epilepsy and its main treatment, AED therapy, on bone health. For patients in whom bone health is a particular concern (eg, those with diagnosed bone disease or with significant risk factors for bone disease, including glucocorticosteroid use), it is best to avoid AEDs known to negatively affect bone. In addition, practitioners should work with other treating physicians to optimize bone health in these patients.
Literature
1.
go back to reference Pack A. Bone health in people with epilepsy: Is it impaired and what are the risk factors? Seizure. 2008;17(2):18.CrossRef Pack A. Bone health in people with epilepsy: Is it impaired and what are the risk factors? Seizure. 2008;17(2):18.CrossRef
2.
go back to reference Souverein PC, Webb DJ, Petri H, et al. Incidence of fractures among epilepsy patients: a population-based retrospective cohort study in the General Practice Research Database. Epilepsia. 2005;46(2):304–10.PubMedCrossRef Souverein PC, Webb DJ, Petri H, et al. Incidence of fractures among epilepsy patients: a population-based retrospective cohort study in the General Practice Research Database. Epilepsia. 2005;46(2):304–10.PubMedCrossRef
3.•
go back to reference Petty SJ, Hill KD, Haber NE, et al. Balance impairment in chronic antiepileptic drug users: a twin and sibling study. Epilepsia 2010, 51(2):280–8. PubMedCrossRef Petty SJ, Hill KD, Haber NE, et al. Balance impairment in chronic antiepileptic drug users: a twin and sibling study. Epilepsia 2010, 51(2):280–8. PubMedCrossRef
4.
go back to reference Vestergaard P. Epilepsy, osteoporosis and fracture risk—a meta-analysis. Acta Neurol Scand. 2005;112(5):277–86.PubMedCrossRef Vestergaard P. Epilepsy, osteoporosis and fracture risk—a meta-analysis. Acta Neurol Scand. 2005;112(5):277–86.PubMedCrossRef
5.
go back to reference Pack AM, Walczak TS. Bone health in women with epilepsy: clinical features and potential mechanisms. Int Rev Neurobiol. 2008;83:305–28.PubMedCrossRef Pack AM, Walczak TS. Bone health in women with epilepsy: clinical features and potential mechanisms. Int Rev Neurobiol. 2008;83:305–28.PubMedCrossRef
6.
go back to reference Persson HB, Alberts KA, Farahmand BY, Tomson T. Risk of extremity fractures in adult outpatients with epilepsy. Epilepsia. 2002;43(7):768–72.PubMedCrossRef Persson HB, Alberts KA, Farahmand BY, Tomson T. Risk of extremity fractures in adult outpatients with epilepsy. Epilepsia. 2002;43(7):768–72.PubMedCrossRef
7.
go back to reference Souverein PC, Webb DJ, Weil JG, Van Staa TP, Egberts AC. Use of antiepileptic drugs and risk of fractures: case-control study among patients with epilepsy. Neurology. 2006;66(9):1318–24.PubMedCrossRef Souverein PC, Webb DJ, Weil JG, Van Staa TP, Egberts AC. Use of antiepileptic drugs and risk of fractures: case-control study among patients with epilepsy. Neurology. 2006;66(9):1318–24.PubMedCrossRef
8.
go back to reference Tsiropoulos I, Andersen M, Nymark T, et al. Exposure to antiepileptic drugs and the risk of hip fracture: a case-control study. Epilepsia. 2008;49(12):2092–9.PubMedCrossRef Tsiropoulos I, Andersen M, Nymark T, et al. Exposure to antiepileptic drugs and the risk of hip fracture: a case-control study. Epilepsia. 2008;49(12):2092–9.PubMedCrossRef
9.
go back to reference Vestergaard P, Rejnmark L, Mosekilde L. Fracture risk associated with use of antiepileptic drugs. Epilepsia. 2004;45(11):1330–7.PubMedCrossRef Vestergaard P, Rejnmark L, Mosekilde L. Fracture risk associated with use of antiepileptic drugs. Epilepsia. 2004;45(11):1330–7.PubMedCrossRef
10.
go back to reference Andress DL, Ozuna J, Tirschwell D, et al. Antiepileptic drug–induced bone loss in young male patients who have seizures. Arch Neurol. 2002;59(5):781–6.PubMedCrossRef Andress DL, Ozuna J, Tirschwell D, et al. Antiepileptic drug–induced bone loss in young male patients who have seizures. Arch Neurol. 2002;59(5):781–6.PubMedCrossRef
11.
go back to reference Farhat G, Yamout B, Mikati MA, et al. Effect of antiepileptic drugs on bone density in ambulatory patients. Neurology. 2002;58(9):1348–53.PubMed Farhat G, Yamout B, Mikati MA, et al. Effect of antiepileptic drugs on bone density in ambulatory patients. Neurology. 2002;58(9):1348–53.PubMed
12.
go back to reference Sato Y, Kondo I, Ishida S, et al. Decreased bone mass and increased bone turnover with valproate therapy in adults with epilepsy. Neurology. 2001;57(3):445–9.PubMed Sato Y, Kondo I, Ishida S, et al. Decreased bone mass and increased bone turnover with valproate therapy in adults with epilepsy. Neurology. 2001;57(3):445–9.PubMed
13.
go back to reference Sheth RD, Wesolowski CA, Jacob JC, et al. Effect of carbamazepine and valproate on bone mineral density. J Pediatr. 1995;127(2):256–62.PubMedCrossRef Sheth RD, Wesolowski CA, Jacob JC, et al. Effect of carbamazepine and valproate on bone mineral density. J Pediatr. 1995;127(2):256–62.PubMedCrossRef
14.
go back to reference Sheth RD, Binkley N, Hermann BP. Gender differences in bone mineral density in epilepsy. Epilepsia. 2008;49(1):125–31.PubMedCrossRef Sheth RD, Binkley N, Hermann BP. Gender differences in bone mineral density in epilepsy. Epilepsia. 2008;49(1):125–31.PubMedCrossRef
15.
go back to reference Samaniego EA, Sheth RD. Bone consequences of epilepsy and antiepileptic medications. Semin Pediatr Neurol. 2007;14(4):196–200.PubMedCrossRef Samaniego EA, Sheth RD. Bone consequences of epilepsy and antiepileptic medications. Semin Pediatr Neurol. 2007;14(4):196–200.PubMedCrossRef
16.
go back to reference Coppola G, Fortunato D, Auricchio G, et al. Bone mineral density in children, adolescents, and young adults with epilepsy. Epilepsia. 2009;50(9):2140–6.PubMedCrossRef Coppola G, Fortunato D, Auricchio G, et al. Bone mineral density in children, adolescents, and young adults with epilepsy. Epilepsia. 2009;50(9):2140–6.PubMedCrossRef
17.
go back to reference Sheth RD, Binkley N, Hermann BP. Progressive bone deficit in epilepsy. Neurology. 2008;70(3):170–6.PubMedCrossRef Sheth RD, Binkley N, Hermann BP. Progressive bone deficit in epilepsy. Neurology. 2008;70(3):170–6.PubMedCrossRef
18.
go back to reference Henderson RC, Lark RK, Gurka MJ, et al. Bone density and metabolism in children and adolescents with moderate to severe cerebral palsy. Pediatrics. 2002;110(1 Pt 1):e5.PubMedCrossRef Henderson RC, Lark RK, Gurka MJ, et al. Bone density and metabolism in children and adolescents with moderate to severe cerebral palsy. Pediatrics. 2002;110(1 Pt 1):e5.PubMedCrossRef
19.
go back to reference 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(3):153–8.PubMedCrossRef 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(3):153–8.PubMedCrossRef
20.
go back to reference Rauchenzauner M, Griesmacher A, Tatarczyk T, et al. Chronic antiepileptic monotherapy, bone metabolism, and body composition in non-institutionalized children. Dev Med Child Neurol. 2010;52(3):283–8.PubMedCrossRef Rauchenzauner M, Griesmacher A, Tatarczyk T, et al. Chronic antiepileptic monotherapy, bone metabolism, and body composition in non-institutionalized children. Dev Med Child Neurol. 2010;52(3):283–8.PubMedCrossRef
21.
go back to reference Nettekoven S, Ströhle A, Trunz B, et al. Effects of antiepileptic drug therapy on vitamin D status and biochemical markers of bone turnover in children with epilepsy. Eur J Pediatr. 2008;167(12):1369–77.PubMedCrossRef Nettekoven S, Ströhle A, Trunz B, et al. Effects of antiepileptic drug therapy on vitamin D status and biochemical markers of bone turnover in children with epilepsy. Eur J Pediatr. 2008;167(12):1369–77.PubMedCrossRef
22.
go back to reference Szulc P, Delmas PD. Biochemical markers of bone turnover in osteoporosis. In: Rosen CJ, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism. New York: Lippincott Williams & Williams; 2009. p. 174–9. Szulc P, Delmas PD. Biochemical markers of bone turnover in osteoporosis. In: Rosen CJ, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism. New York: Lippincott Williams & Williams; 2009. p. 174–9.
23.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
24.
go back to reference Sowers M, Crutchfield M, Bandekar R, et al. Bone mineral density and its change in pre- and perimenopausal white women: the Michigan Bone Health Study. J Miner Res. 1998;13(7):1134–40.CrossRef Sowers M, Crutchfield M, Bandekar R, et al. Bone mineral density and its change in pre- and perimenopausal white women: the Michigan Bone Health Study. J Miner Res. 1998;13(7):1134–40.CrossRef
25.
go back to reference 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. Neurology. 2004;62(11):2051–7.PubMed 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. Neurology. 2004;62(11):2051–7.PubMed
26.
go back to reference Verrotti A, Greco R, Morgese G, Chiarelli F. Increased bone turnover in epileptic patients treated with carbamazepine. Ann Neurol. 2000;47(3):385–8.PubMedCrossRef Verrotti A, Greco R, Morgese G, Chiarelli F. Increased bone turnover in epileptic patients treated with carbamazepine. Ann Neurol. 2000;47(3):385–8.PubMedCrossRef
27.
go back to reference Verrotti A, Greco R, Latini G, Morgese G, Chiarelli F. Increased bone turnover in prepubertal, pubertal, and postpubertal patients receiving carbamazepine. Epilepsia. 2002;43(12):1488–92.PubMedCrossRef Verrotti A, Greco R, Latini G, Morgese G, Chiarelli F. Increased bone turnover in prepubertal, pubertal, and postpubertal patients receiving carbamazepine. Epilepsia. 2002;43(12):1488–92.PubMedCrossRef
28.
go back to reference Kim SH, Lee JW, Choi KG, Chung HW, Lee HW. A 6-month longitudinal study of bone mineral density with antiepileptic drug monotherapy. Epilepsy and Behavior. 2007;10(2):291–5.PubMedCrossRef Kim SH, Lee JW, Choi KG, Chung HW, Lee HW. A 6-month longitudinal study of bone mineral density with antiepileptic drug monotherapy. Epilepsy and Behavior. 2007;10(2):291–5.PubMedCrossRef
29.
go back to reference Mintzer S, Boppana P, Toguri J, et al. Vitamin D levels and bone turnover in epilepsy taking carbamazepine or oxcarbazepine. Epilepsia. 2006;47(3):510–5.PubMedCrossRef Mintzer S, Boppana P, Toguri J, et al. Vitamin D levels and bone turnover in epilepsy taking carbamazepine or oxcarbazepine. Epilepsia. 2006;47(3):510–5.PubMedCrossRef
30.
go back to reference Cansu A, Yesilkaya E, Serdaroğlu A, et al. Evaluation of bone turnover in epileptic children using oxcarbazepine. Pediatr Neurol. 2008;39(4):266–71.PubMedCrossRef Cansu A, Yesilkaya E, Serdaroğlu A, et al. Evaluation of bone turnover in epileptic children using oxcarbazepine. Pediatr Neurol. 2008;39(4):266–71.PubMedCrossRef
31.
go back to reference Gou CY, Ronen GM, Atkinson SA. Long-term valproate and lamotrigine treatment may be a marker for reduced growth and bone mass in children with epilepsy. Epilepsia. 2001;42(9):1141–7. Gou CY, Ronen GM, Atkinson SA. Long-term valproate and lamotrigine treatment may be a marker for reduced growth and bone mass in children with epilepsy. Epilepsia. 2001;42(9):1141–7.
32.
go back to reference 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;17(2):232–7.PubMedCrossRef 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;17(2):232–7.PubMedCrossRef
33.•
go back to reference Ensrud KE, Walczak TS, Blackwell TL, et al. Antiepileptic drug use and rates of hip bone loss in older men: a prospective study. Neurology 2008, 71(10):723–30.PubMedCrossRef Ensrud KE, Walczak TS, Blackwell TL, et al. Antiepileptic drug use and rates of hip bone loss in older men: a prospective study. Neurology 2008, 71(10):723–30.PubMedCrossRef
34.
go back to reference Sheth RD, Hermann BP. Bone mineral density with lamotrigine monotherapy for epilepsy. Pediatr Neurol. 2007;37(4):250–4.PubMedCrossRef Sheth RD, Hermann BP. Bone mineral density with lamotrigine monotherapy for epilepsy. Pediatr Neurol. 2007;37(4):250–4.PubMedCrossRef
35.
go back to reference Pierce Jr WM, Nardin GF, Fuqua MF, et al. Effect of chronic carbonic anhydrase inhibitor therapy on bone and mineral density in white women. J Bone Miner Res. 1991;6(4):347–54.PubMedCrossRef Pierce Jr WM, Nardin GF, Fuqua MF, et al. Effect of chronic carbonic anhydrase inhibitor therapy on bone and mineral density in white women. J Bone Miner Res. 1991;6(4):347–54.PubMedCrossRef
36.
go back to reference Nissen-Meyer LS, Svalheim S, Tauboll E, et al. Levetiracetam, phenytoin, and valproate act differently on rat bone mass, structure, and metabolism. Epilepsia. 2007;48(10):1–11.CrossRef Nissen-Meyer LS, Svalheim S, Tauboll E, et al. Levetiracetam, phenytoin, and valproate act differently on rat bone mass, structure, and metabolism. Epilepsia. 2007;48(10):1–11.CrossRef
37.
go back to reference Pascussi JM, Robert A, Nguyen M, et al. Possible involvement of pregnane X receptor-enhanced CYP 24 expression in drug-induced osteomalacia. J Clin Invest. 2005;115(1):177–86.PubMed Pascussi JM, Robert A, Nguyen M, et al. Possible involvement of pregnane X receptor-enhanced CYP 24 expression in drug-induced osteomalacia. J Clin Invest. 2005;115(1):177–86.PubMed
38.
go back to reference Zhou C, Assem M, Tay JC, et al. Steroid and xenobiotic receptor and vitamin D receptor crosstalk mediates CYP24 expression and drug-induced osteomalacia. J Clin Invest. 2006;116(6):1703–12.PubMedCrossRef Zhou C, Assem M, Tay JC, et al. Steroid and xenobiotic receptor and vitamin D receptor crosstalk mediates CYP24 expression and drug-induced osteomalacia. J Clin Invest. 2006;116(6):1703–12.PubMedCrossRef
39.
go back to reference Pack AM, Morrell MJ, Marcus R, et al. Bone mass and turnover in women with epilepsy on antiepileptic drug monotherapy. Ann Neurol. 2005;57(2):781–6.CrossRef Pack AM, Morrell MJ, Marcus R, et al. Bone mass and turnover in women with epilepsy on antiepileptic drug monotherapy. Ann Neurol. 2005;57(2):781–6.CrossRef
40.
go back to reference Stephen LJ, McLellan AR, Harrison JH, et al. Bone density and antiepileptic drugs: a case-controlled study. Seizure. 1999;8(6):339–42.PubMedCrossRef Stephen LJ, McLellan AR, Harrison JH, et al. Bone density and antiepileptic drugs: a case-controlled study. Seizure. 1999;8(6):339–42.PubMedCrossRef
41.
go back to reference Bhatt R, Bhatt S, Hameed M, Rameshwar P, Siegel A. Amygdaloid kindled seizures can induce functional and pathological changes in thymus of rat: role of the sympathetic nervous system. Neurobiol Dis. 2006;21(1):127–37.PubMedCrossRef Bhatt R, Bhatt S, Hameed M, Rameshwar P, Siegel A. Amygdaloid kindled seizures can induce functional and pathological changes in thymus of rat: role of the sympathetic nervous system. Neurobiol Dis. 2006;21(1):127–37.PubMedCrossRef
42.•
go back to reference Lambrinoudaki I, Kaparos G, Armeni 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.PubMedCrossRef Lambrinoudaki I, Kaparos G, Armeni 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.PubMedCrossRef
43.
go back to reference Pack AM. Genetic variation may clarify the relationship between epilepsy, antiepileptic drugs, and bone health. Eur J Neurol. 2011;18(1):3–4.PubMedCrossRef Pack AM. Genetic variation may clarify the relationship between epilepsy, antiepileptic drugs, and bone health. Eur J Neurol. 2011;18(1):3–4.PubMedCrossRef
44.
go back to reference 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;19:419–28.PubMedCrossRef 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;19:419–28.PubMedCrossRef
46.
go back to reference Mikati MA, Dib L, Yamout B, et al. Two randomized vitamin D trials in ambulatory patients on anticonvulsants: impact on bone. Neurology. 2006;67(11):2005–14.PubMedCrossRef Mikati MA, Dib L, Yamout B, et al. Two randomized vitamin D trials in ambulatory patients on anticonvulsants: impact on bone. Neurology. 2006;67(11):2005–14.PubMedCrossRef
47.
Metadata
Title
Treatment of Epilepsy to Optimize Bone Health
Author
Alison M. Pack, MD, MPH
Publication date
01-08-2011
Publisher
Current Science Inc.
Published in
Current Treatment Options in Neurology / Issue 4/2011
Print ISSN: 1092-8480
Electronic ISSN: 1534-3138
DOI
https://doi.org/10.1007/s11940-011-0133-x

Other articles of this Issue 4/2011

Current Treatment Options in Neurology 4/2011 Go to the issue