Osteoporosis and Antiepileptic Medications

Antiepileptic medication use is correlated with decreased bone mineral density in children and adults. [Pack: 2003].[Valsamis: 2006] [Sheth: 2004] [Farhat: 2002] and fractures are increased two to six times in patients with epilepsy compared to the general population. [Mattson: 2004] [Vestergaard: 1999] As many children who start on antiepileptic medications in childhood will be on those medications for many years, the fracture risk by adulthood is substantial. The enzyme-inducing drugs phenobarbital, carbamazepine, phenytoin and benzodiazepines (e.g., klonopin and valium) decrease bone density through effects on vitamin D metabolism and subsequent hypocalcemia. [Valsamis: 2006] Valproic acid is thought to directly act on the bone, increasing activity of the osteoclasts, the cells responsible for bone breakdown in the dynamic process of remodeling. [Valsamis: 2006] Not as much information is available regarding the newer antiepileptic drugs, but preliminary reports suggest they may have less of an effect on bone density than the older medications. [Farhat: 2002]

Many children on these medications may also have restricted movement due to underlying illness such as cerebral palsy, which also decreases bone mineral density. Children with CP have a higher fracture rate than the general population [Stevenson: 2006] and this fracture rate may be even higher in children with CP on antiepileptic medications. [Leet: 2006] Children with epilepsy may also be at an increased risk for falls due to seizures and ataxia, if present.

Surveillance and Treatment

Consider checking bone mineral density by Dexascan (Dual-energy X-ray Absorptiometry) (See Services for where to order) in children on antiepileptic medications for prolonged periods, especially those with decreased physical activity, on a periodic basis, approximately yearly. Although there are problems interpreting these numbers in children, the fracture risk appears to correlate with the bone mineral density. Serum calcium phosphate, alkaline phosphatase, PTH and vitamin D levels should also be measured periodically. [Valsamis: 2006]

Children with decreased mobility and/or those on antiepileptic medications should have their diets optimized for calcium and vitamin D. Consideration of a referral to endocrinology should be given when children on antiepileptic medication have fractures and/or low bone mineral densities. Although there are no controlled treatment guidelines, children with a history of fractures and low bone mineral density may benefit by treatment with bisphosphonates, either weekly or monthly orally (alendronate or ibandronate) or every two months by IV infusion (pamidronate). [Valsamis: 2006] [Pack: 2003]


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Helpful Articles

Sheth RD.
Bone health in pediatric epilepsy.
Epilepsy Behav. 2004;5 Suppl 2:S30-5. PubMed abstract

Samaniego EA, Sheth RD.
Bone consequences of epilepsy and antiepileptic medications.
Semin Pediatr Neurol. 2007;14(4):196-200. PubMed abstract

Authors & Reviewers

Initial publication: September 2008; last update/revision: June 2011
Current Authors and Reviewers:
Author: Lynne M. Kerr, MD, PhD

Page Bibliography

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. PubMed abstract

Leet AI, Mesfin A, Pichard C, Launay F, Brintzenhofeszoc K, Levey EB, D Sponseller P.
Fractures in children with cerebral palsy.
J Pediatr Orthop. 2006;26(5):624-7. PubMed abstract

Mattson RH, Gidal BE.
Fractures, epilepsy, and antiepileptic drugs.
Epilepsy Behav. 2004;5 Suppl 2:S36-40. PubMed abstract

Pack, Alison.
The Association between Antiepileptic Drugs and Bone Disease.
Epilepsy Curr. 2003;3(3):91-95. PubMed abstract

Sheth RD.
Bone health in pediatric epilepsy.
Epilepsy Behav. 2004;5 Suppl 2:S30-5. PubMed abstract

Stevenson RD, Conaway M, Barrington JW, Cuthill SL, Worley G, Henderson RC.
Fracture rate in children with cerebral palsy.
Pediatr Rehabil. 2006;9(4):396-403. PubMed abstract

Valsamis HA, Arora SK, Labban B, McFarlane SI.
Antiepileptic drugs and bone metabolism.
Nutr Metab (Lond). 2006;3:36. PubMed abstract / Full Text

Vestergaard P, Tigaran S, Rejnmark L, Tigaran C, Dam M, Mosekilde L.
Fracture risk is increased in epilepsy.
Acta Neurol Scand. 1999;99(5):269-75. PubMed abstract