An update on the problem of osteoporosis in people with epilepsy taking antiepileptic drugs

ABSTRACT

Introduction: Antiepileptic drugs (AEDs) have been associated with a negative impact on bone health. Comorbid disorders in patients with epilepsy may require drugs exerting a pro-osteoporotic effect, so a possibility of untoward interactions with AEDs is probable.

Areas covered: This review discusses evidence related to the deteriorating influence of AEDs on bone, demonstrating generally stronger negative effects of conventional AEDs. Lamotrigine seems to be a safer AED in this regard. Further, literature data indicate that generally AEDs can lower the serum concentration of vitamin D. Importantly, pediatric patients are of greater risk of bone problems during therapy with AEDs, which is probably due to their effects on bone-forming processes.

Expert opinion: Supplementation with vitamin D and calcium is frequently recommended in patients taking AEDs chronically. Whether to add a bisphosphonate remains an open question due to the limited data on this issue. A possibility of negative interactions exists between AEDs and other pro-osteoporotic drugs: glucocorticoids, proton pump inhibitors and aromatase inhibitors. Depression is a frequent comorbidity in patients with epilepsy. Clinical data indicate that antidepressant drugs may also increase the risk of fractures. Again, patients with epilepsy and depression may be exposed to a greater risk of osteoporosis.

KEYWORDS:

• Antiepileptics
• bisphosphonates
• bone health
• calcium supplementation
• fractures
• osteoporosis
• vitamin D supplementation

Article highlights

• Antiepileptic drugs are prescribed not only to patients with epilepsy but also for reasons other than epilepsy, which include chronic pain, bipolar disorder, migraine and other neurologic/psychiatric conditions.

• Around 50 million people worldwide may be affected by osteoporosis connected with millions of osteoporotic fractures each year.

• Patients with epilepsy are at increased fracture risk due to seizures and to the adverse effects of antiepileptic drugs, which may decrease the serum vitamin D concentration and calcium absorption resulting in a reduced bone mineral density. The negative effects of antiepileptic drugs on bone health may be also attributed to the reduction of serum vitamin K concentration disturbing the activity of osteoblasts.

• Pediatric patients on antiepileptic drugs are more susceptible to their negative effect on bone health because of their additional influence on bone-forming processes.

• Supplementation with vitamin D and calcium is recommended to prevent bone loss in patients on antiepileptic drugs. Limited studies have been conducted on whether to add a bisphosphonate to the above supplementation. The existing results favour the use of bisphosphonates in order to prevent osteoporosis in such patients.

• Depression is a frequent comorbidity in patients with epilepsy. Clinical data indicate that antidepressant drugs may also have a negative impact on bone. A possible negative interaction between antiepileptic and antidepressant drugs may exist in this respect.

This box summarizes key points contained in the article.

Acknowledgments

The authors wish to express their thanks to Mr. Joseph A Banach for reviewing the grammar.

Declaration of interest

SJ Czuczwar has received financial support from Bayer, GlaxoSmithKline, Janssen, Novartis and Sanofi-Aventis for lecturing. He is also the recipient of an unrestricted grant from GlaxoSmithKline. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Funding

This paper was not funded.