A review of the effect of anticonvulsant medications on bone mineral density and fracture risk.
BACKGROUND
Osteoporosis and seizure disorders are common diagnoses in older adults and often occur concomitantly.


OBJECTIVE
The goal of this review was to discuss the current hypothesis for the pathogenesis of anticonvulsant-induced bone density loss and the evidence regarding the risk for osteoporosis and fractures in older individuals.


METHODS
A review of the literature was performed, searching in MEDLINE and CINAHL for articles published between 1990 and October 2009 with the following search terms: anticonvulsant OR antiepileptic; AND osteoporosis OR bone density OR fracture OR absorptiometry, photon. Studies within the pediatric population, cross-sectional studies, and studies whose results were published in a language other than English were excluded.


RESULTS
A search of the published literature yielded >300 results, of which 24 met the inclusion and exclusion criteria and were included in this review. Hepatic enzyme induction by certain anticonvulsant medications appears to contribute to increased metabolism of 25-hydroxyvitamin D to inactive metabolites, which results in metabolic bone disease. There is increasing evidence that anticonvulsant use is associated with a higher risk of osteoporosis and clinical fractures, especially among older agents such as phenobarbital, carbamazepine, phenytoin, and valproate. Several observational studies suggest a class effect among anticonvulsant agents, associated with clinically significant reductions in bone mineral density and fracture risk. The use of anticonvulsant medications increases the odds of fracture by 1.2 to 2.4 times. However, only 2 large-scale observational studies have specifically examined the risk among those aged >65 years. This review also identified a randomized controlled trial whose results suggest that supplementation with high-dose vitamin D may be associated with increased bone mineral density in patients taking anticonvulsant medications. However, no randomized controlled trials investigating therapeutic agents to prevent fracture in this population were identified. Consequently, there are no formal practice guidelines for the monitoring, prevention, and management of bone disease among those taking anticonvulsants.


CONCLUSIONS
Observational studies suggest an association between use of anticonvulsant medications, reduced bone mineral density, and increased fracture risk. Randomized clinical trials are needed to guide the management of bone disease among those who use anticonvulsants.
Division of Geriatrics, Department of Internal Medicine, Duke University Medical Center, Durham, North Carolina, USA. r.lee@duke.edu
Richard H
RH
Lee
Kenneth W
KW
Lyles
Cathleen
C
Colón-Emeric
D000367:Age Factors; D000368:Aged; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects*; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D016022:Case-Control Studies; D050723:Fractures, Bone / Q000139:chemically induced* / Q000453:epidemiology* / Q000503:physiopathology; D006801:Humans; D012307:Risk Factors
D000927:Anticonvulsants