J Clin Neurol.  2012 Mar;8(1):65-68. 10.3988/jcn.2012.8.1.65.

May Long Term Oxcarbazepine Treatment Be Lead to Secondary Hyperparathyroidism?

• Babacan O
• Karaoglu A
• Vurucu S
• Yesilkaya
• Yesilyurt
• Cayci T
• Gulgun M
• Unay B
• Akin R
• Ozcan O

• KMID: 2287619
• DOI: http://doi.org/10.3988/jcn.2012.8.1.65

Abstract

BACKGROUND AND PURPOSE
The adverse effects of newer antiepileptic drugs are not well-known. This study assessed the impact of oxcarbazepine (OXC) treatment on bone turnover.
METHODS
Forty-four children with idiopathic focal (and/or secondarily generalized) epilepsy who had been treated with OXC for more than 1 year were compared with 33 healthy, age- and sex-matched children. Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, osteocalcin, calcitonin, and 25-hydroxyvitamin D, and bone mineral density were measured to evaluate and compare bone mineralization between the two groups.
RESULTS
The serum levels of calcium, osteocalcin, 25-hydroxyvitamin D, and bone mineral density did not differ significantly between the study and control groups. However, serum levels of parathyroid hormone, alkaline phosphatase, phosphorus, and calcitonin differed significantly between the two groups.
CONCLUSIONS
These findings suggest that OXC treatment leads to secondary hyperparathyroidism with high-turnover bone disease and/or impaired intestinal calcium absorption.

Keyword

oxcarbazepine; bone mineralization; children

MeSH Terms

Absorption
Alkaline Phosphatase
Anticonvulsants
Bone Density
Bone Diseases
Calcification, Physiologic
Calcitonin
Calcium
Carbamazepine
Child
Epilepsy
Humans
Hyperparathyroidism, Secondary
Osteocalcin
Parathyroid Hormone
Phosphorus
Vitamin D
Alkaline Phosphatase
Anticonvulsants
Calcitonin
Calcium
Carbamazepine
Osteocalcin
Parathyroid Hormone
Phosphorus
Vitamin D

Reference

1. Dent CE, Richens A, Rowe DJ, Stamp TC. Osteomalacia with long-term anticonvulsant therapy in epilepsy. Br Med J. 1970. 4:69–72.

2. Bogliun G, Beghi E, Crespi V, Delodovici L, d'Amico P. Anticonvulsant drugs and bone metabolism. Acta Neurol Scand. 1986. 74:284–288.

3. Pack AM, Morrell MJ. Adverse effects of antiepileptic drugs on bone structure: epidemiology, mechanisms and therapeutic implications. CNS Drugs. 2001. 15:633–642.

4. Coppola G, Fortunato D, Auricchio G, Mainolfi C, Operto FF, Signoriello G, et al. Bone mineral density in children, adolescents, and young adults with epilepsy. Epilepsia. 2009. 50:2140–2146.

5. Babayigit A, Dirik E, Bober E, Cakmakci H. Adverse effects of antiepileptic drugs on bone mineral density. Pediatr Neurol. 2006. 35:177–181.

6. Verrotti A, Greco R, Latini G, Morgese G, Chiarelli F. Increased bone turnover in prepubertal, pubertal, and postpubertal patients receiving carbamazepine. Epilepsia. 2002. 43:1488–1492.

7. Mintzer S, Boppana P, Toguri J, DeSantis A. Vitamin D levels and bone turnover in epilepsy patients taking carbamazepine or oxcarbazepine. Epilepsia. 2006. 47:510–515.

8. Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. 2010. 51:676–685.

9. Pack AM, Morrell MJ. Epilepsy and bone health in adults. Epilepsy Behav. 2004. 5:Suppl 2. S24–S29.

10. Pack AM, Gidal B, Vazquez B. Bone disease associated with antiepileptic drugs. Cleve Clin J Med. 2004. 71:Suppl 2. S42–S48.

11. Crosley CJ, Chee C, Berman PH. Rickets associated with long-term anticonvulsant therapy in a pediatric outpatient population. Pediatrics. 1975. 56:52–57.

12. Schmitt BP, Nordlund DJ, Rodgers LA. Prevalence of hypocalcemia and elevated serum alkaline phosphatase in patients receiving chronic anticonvulsant therapy. J Fam Pract. 1984. 18:873–877.

13. Hahn TJ, Scharp CR, Richardson CA, Halstead LR, Kahn AJ, Teitelbaum SL. Interaction of diphenylhydantoin (phenytoin) and phenobarbital with hormonal mediation of fetal rat bone resorption in vitro. J Clin Invest. 1978. 62:406–414.

14. Weinstein RS, Bryce GF, Sappington LJ, King DW, Gallagher BB. Decreased serum ionized calcium and normal vitamin D metabolite levels with anticonvulsant drug treatment. J Clin Endocrinol Metab. 1984. 58:1003–1009.

15. 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. 41:1130–1135.

16. Välimäki MJ, Tiihonen M, Laitinen K, Tähtelä R, Kärkkäinen M, Lamberg-Allardt C, et al. 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. 9:631–637.

17. Schoppet M, Shanahan CM. Role for alkaline phosphatase as an inducer of vascular calcification in renal failure? Kidney Int. 2008. 73:989–991.

18. Verrotti A, Greco R, Morgese G, Chiarelli F. Increased bone turnover in epileptic patients treated with carbamazepine. Ann Neurol. 2000. 47:385–388.

19. Koch HU, Kraft D, von Herrath D, Schaefer K. Influence of diphenylhydantoin and phenobarbital on intestinal calcium transport in the rat. Epilepsia. 1972. 13:829–834.

20. Vernillo AT, Rifkin BR, Hauschka PV. Phenytoin affects osteocalcin secretion from osteoblastic rat osteosarcoma 17/2.8 cells in culture. Bone. 1990. 11:309–312.