Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
BMC Pediatrics
Published in: BMC Pediatrics 1/2016

Open Access 01-12-2016 | Research article

Potential effects of valproate and oxcarbazepine on growth velocity and bone metabolism in epileptic children- a medical center experience

Authors: Chien-Ming Lin, Hueng-Chuen Fan, Tsu-Yi Chao, Der-Ming Chu, Chi-Chieh Lai, Chih-Chien Wang, Shyi-Jou Chen

Published in: BMC Pediatrics | Issue 1/2016

Login to get access

Abstract

Background

Children with longstanding use of antiepileptic drugs (AEDs) are susceptible to developing low bone mineral density and an increased fracture risk. However, the literature regarding the effects of AEDs on growth in epileptic children is limited. The aim of this study was to investigate the potential effects of valproate (VPA) and/or oxcarbazepine (OXC) therapy on growth velocity and bone metabolism.

Methods

Seventy-three ambulatory children (40 boys and 33 girls) with epilepsy, aged between 1 and 18 years (mean age 9.8 ± 4.1 years), were evaluated for growth velocity before and for 1 year after VPA and/or OXC treatment. The bone resorption marker serum tartrate-resistant acid phosphatase 5b (TRAcP5b) and the bone formation marker serum bone-specific alkaline phosphatase (BAP) were measured post-AEDs therapy for 1 year.

Results

The difference in growth velocity (ΔHt) and body weight change (ΔWt) between pre- and post-AEDs treatment were -1.0 ± 2.8 cm/year (P < 0.05) and 0.1 ± 3.9 kg/year (P = 0.84), respectively. The study population had serum TRAcP5b-SDS of -1.6 ± 1.2 and BAP-SDS of 1.7 ± 3.7 compared with sex- and age-matched healthy children. Significant correlation between serum TRAcP 5b and BAP activities was noted (r = 0.60, p < 0.001). There was a positive correlation between growth velocity and serum TRAcP 5b activity after AED treatment (r = 0.42, p < 0.01). No correlation was found between ΔHt, ΔWt, serum TRAcP 5b, BAP activity and types of AEDs.

Conclusion

Growth velocity was significantly decreased in epileptic children after 1 year of VPA and/or OXC treatment. The effect of VPA and/or OXC therapy on dysregulation of bone metabolism might play a crucial role in physical growth.
Appendix
Available only for authorised users
Literature
1.
Pack AM, Gidal B, Vazquez B. Bone disease associated with antiepileptic drugs. Cleve Clin J Med. 2004;71 Suppl 2:S42–8.CrossRefPubMed
2.
Chou IJ, Lin KL, Wang HS, Wang CJ. Evaluation of bone mineral density in children receiving carbamazepine or valproate monotherapy. Acta Paediatr Taiwan. 2007;48(6):317–22.PubMed
3.
Phabphal K, Limapichat K, Sathirapanya P, Setthawatcharawanich S, Leelawattana R, Thammakumpee N, et al. Bone mineral density following long-term use of antiepileptic drugs in a tropical Asian country. Epileptic Disord. 2008;10(3):213–8.PubMed
4.
Baroncelli GI, Bertelloni S, Sodini F, Saggese G. Osteoporosis in children and adolescents: etiology and management. Paediatr Drugs. 2005;7(5):295–323.CrossRefPubMed
5.
Ecevit C, Aydoğan A, Kavakli T, Altinöz S. Effect of carbamazepine and valproate on bone mineral density. Pediatr Neurol. 2004;31(4):279–82.CrossRefPubMed
6.
Telci A, Cakatay U, Kurt BB, Kayali R, Sivas A, Akcay T, et al. Changes in bone turnover and deoxypyridinoline levels in epileptic patients. Clin Chem Lab Med. 2000;38(1):47–50.CrossRefPubMed
7.
Onodera K, Takahashi A, Mayanagi H, Wakabayashi H, Kamei J, Shinoda H. Phenytoin-induced bone loss and its prevention with alfacalcidol or calcitriol in growing rats. Calcif Tissue Int. 2001;69(2):109–16.CrossRefPubMed
8.
Guo 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.CrossRefPubMed
9.
Rattya J, Vainionpaa L, Knip M, Lanning P, Isojarvi JI. The effects of valproate, carbamazepine, and oxcarbazepine on growth and sexual maturation in girls with epilepsy. Pediatrics. 1999;103(3):588–93.CrossRefPubMed
10.
Engel Jr J, International League Against Epilepsy (ILAE). A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia. 2001;42(6):796–803.CrossRefPubMed
11.
Halleen JM, Alatalo SL, Suominen H, Cheng S, Janckila AJ, Vaananen HK. Tartrate-resistant acid phosphatase 5b: a novel serum marker of bone resorption. J Bone Miner Res. 2000;15(7):1337–45.CrossRefPubMed
12.
Janckila AJ, Takahashi K, Sun SZ, Yam LT. Tartrate-resistant acid phosphatase isoform 5b as serum marker for osteoclastic activity. Clin Chem. 2001;47(1):74–80.PubMed
13.
Chao TY, Ho CL, Lee SH, Chen MM, Janckila A, Yam LT. Tartrate-resistant acid phosphatase 5b as a serum marker of bone metastasis in breast cancer patients. J Biomed Sci. 2004;11(4):511–6.CrossRefPubMed
14.
Chen W, Chang MH. New growth charts for Taiwanese children and adolescents based on World Health Organization standards and health-related physical fitness. Pediatr Neonatol. 2010;51(2):69–79.CrossRefPubMed
15.
Chen CJ, Chao TY, Janckila AJ, Cheng SN, Ku CH, Chu DM. Evaluation of the activity of tartrate-resistant acid phosphatase isoform 5b in normal Chinese children--a novel marker for bone growth. J Pediatr Endocrinol Metab. 2005;18(1):55–62.CrossRefPubMed
16.
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. Arch Neurol. 2002;59(5):781–6.CrossRefPubMed
17.
Boluk A, Guzelipek M, Savli H, Temel I, Ozişik HI, Kaygusuz A. The effect of valproate on bone mineral density in adult epileptic patients. Pharmacol Res. 2004;50(1):93–7.CrossRefPubMed
18.
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 Behav. 2003;4(2):169–74.CrossRefPubMed
19.
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(3):283–8.CrossRefPubMed
20.
Välimäki MJ, Tiihonen MLK, Tähtelä RKM, Lamberg-Allardt C, Mäkelä P, Tunninen R. Bone mineral density measured by dual-energy x-ray absorptiometry and novel markers of bone formation and resorption in patients on antiepileptic drugs. J Bone Miner Res. 1994;9(5):631–7.CrossRefPubMed
21.
Fitzpatrick LA. Pathophysiology of bone loss in patients receiving anticonvulsant therapy. Epilepsy Behav. 2004;5 Suppl 2:S3–15.CrossRefPubMed
22.
Rauchenzauner M, Haberlandt E, Scholl-Burgi S, Karall D, Schoenherr E, Tatarczyk T, et al. Effect of valproic acid treatment on body composition, leptin and the soluble leptin receptor in epileptic children. Epilepsy Res. 2008;80(2-3):142–9.CrossRefPubMed
23.
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(9):1348–53.CrossRefPubMed
24.
Rieger-Wettengl G, Tutlewski B, Stabrey A, Rauch F, Herkenrath P, Schauseil-Zipf U, et al. Analysis of the musculoskeletal system in children and adolescents receiving anticonvulsant monotherapy with valproic acid or carbamazepine. Pediatrics. 2001;108(6):E107.CrossRefPubMed
25.
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.CrossRefPubMed
26.
El-Hajj Fuleihan G, Dib L, Yamout B, Sawaya R, Mikati MA. Predictors of bone density in ambulatory patients on antiepileptic drugs. Bone. 2008;43(1):149–55.CrossRefPubMed
27.
Kim SH, Lee JW, Choi KG, Chung HW, Lee HW. A 6-month longitudinal study of bone mineral density with antiepileptic drug monotherapy. Epilepsy Behav. 2007;10(2):291–5.CrossRefPubMed
28.
Akin R, Okutan V, Sarici U, Altunbas A, Gökçay E. Evaluation of bone mineral density in children receiving antiepileptic drugs. Pediatr Neurol. 1998;19(2):129–31.CrossRefPubMed
29.
Guerra-Menéndez L, Sádaba MC, Puche JE, Lavandera JL, de Castro LF, de Gortázar AR, et al. IGF-I increases markers of osteoblastic activity and reduces bone resorption via osteoprotegerin and RANK-ligand. J Transl Med. 2013;11:271.CrossRefPubMedPubMedCentral
30.
Amin S, Riggs BL, Atkinson EJ, Oberg AL, Melton 3rd LJ, Khosla S. A potentially deleterious role of IGFBP-2 on bone density in aging men and women. J Bone Miner Res. 2004;19(7):1075–83.CrossRefPubMed
31.
Amin S, Riggs BL, Melton 3rd LJ, Achenbach SJ, Atkinson EJ, Khosla S. High serum IGFBP-2 is predictive of increased bone turnover in aging men and women. J Bone Miner Res. 2007;22(6):799–807.CrossRefPubMed
32.
Yamamoto M, Sugimoto T. Effects of growth hormone replacement therapy on bone metabolism. Clin Calcium. 2014;24(6):903–9.PubMed
Metadata
Title
Potential effects of valproate and oxcarbazepine on growth velocity and bone metabolism in epileptic children- a medical center experience
Authors
Chien-Ming Lin
Hueng-Chuen Fan
Tsu-Yi Chao
Der-Ming Chu
Chi-Chieh Lai
Chih-Chien Wang
Shyi-Jou Chen
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2016
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-016-0597-7

Other articles of this Issue 1/2016

BMC Pediatrics 1/2016 Go to the issue

Research article

Unintentional childhood injury: a controlled comparison of behavioral characteristics

Study protocol

“GET-UP” study rationale and protocol: a cluster randomised controlled trial to evaluate the effects of reduced sitting on toddlers’ cognitive development

Research article

The successful accomplishment of nutritional and clinical outcomes via the implementation of a multidisciplinary nutrition support team in the neonatal intensive care unit

Research article

Facilitators and barriers of breastfeeding late preterm infants according to mothers’ experiences

Case report

Duodenal atresia with apple-peel configuration of the ileum and absent superior mesenteric artery

Erratum

Erratum to: Neonatal Hyperbilirubinemia in infants with G6PD c.563C > T Variant