Bone mineral density of epileptic patients on long-term antiepileptic drug therapy: a quantitative digital radiography study

Kubota, Fumio; Kifune, Akira; Shibata, Nobuyoshi; Akata, Takusirou; Takeuchi, Kazuo; Takahashi, Shigeru; Ohsawa, Minoru; Takama, Fumiko

doi:10.1016/s0920-1211(98)00077-1

Cited by 38 publications

(15 citation statements)

References 8 publications

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“…Three prior prospective studies 5,10,21 examined AED use and rates of bone loss, but were limited by small sample size, selection bias, absence of a comparison group of subjects not taking AEDs, and lack of adjustment for potential confounders. A prior analysis 22 from the Study of Osteoporotic Fractures (SOF), a prospective study of a large cohort of older community-dwelling women similar in design to MrOS, reported that phenytoin users had higher adjusted rates of hip bone loss compared with nonusers of AEDs.…”

Section: Resultsmentioning

confidence: 99%

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Antiepileptic drug use and rates of hip bone loss in older men

Ensrud¹,

et al. 2008

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Objective: To test the hypotheses that older community dwelling men taking non-enzymeinducing antiepileptic drugs (NEIAEDs) and those taking enzyme-inducing antiepileptic drugs (EIAEDs) have increased rates of hip bone loss. Methods:We ascertained antiepileptic drug (AED) use (interviewer-administered questionnaire with verification of use by containers) and measured hip bone mineral density (BMD) (using dual energy x-ray absorptiometry) at baseline and an average of 4.6 years later in a cohort of 4,222 older community-dwelling men enrolled in the Osteoporotic Fractures in Men study. Men were categorized as nonusers (no AED use at either examination, n ϭ 4060), NEIAED user (use of NEIAED only at either examination, n ϭ 100), or EIAED user (use of EIAED only at either examination, n ϭ 62). Results:After adjustment for multiple potential confounders (age, race, clinic site, health status, pain interfering with work or activity, physical activity, smoking status, alcohol use, total calcium intake, diabetes, chronic kidney disease, vitamin D supplement use, bisphosphonate use, selective serotonin reuptake inhibitor use, inability to rise from a chair, body mass index, and baseline BMD), the average rate of decline in total hip BMD was Ϫ0.35%/year among nonusers compared with Ϫ0.53%/year among NEIAED users (p ϭ 0.04) and Ϫ0.46%/year among EIAED users (p ϭ 0.31). Multivariable adjusted rate of loss was Ϫ0.60%/year among men taking NEIAED at both examinations, Ϫ0.51%/year among men taking NEIAED at one examination only, and Ϫ0.35%/ year among nonusers (p for trend ϭ 0.03). Findings were similar at hip subregions. Conclusion:Use of non-enzyme-inducing antiepileptic drugs was independently associated with increased rates of hip bone loss in this cohort of older community-dwelling men. Antiepileptic drug (AED) use may be associated with higher rates of bone loss because AED use may have adverse effects on bone metabolism. 1 On the other hand, AED use may be a marker of factors such as poor health, medical conditions, lifestyle behaviors, and neuromuscular impairments that are associated with greater rates of bone loss. Thus, an apparent association between AED use and bone loss might be due to these confounding factors rather than an effect of AED use.

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Section: Resultsmentioning

confidence: 99%

“…2 Evidence linking phenytoin (EIAED) [3][4][5][6][7] and phenobarbital (EIAED) 4,5 to lower bone mineral density (BMD) is generally consistent with this theory. However, carbamazepine (EIAED) [6][7][8][9][10] has not been associated with lower BMD, while valproic acid (nonenzyme-inducing AED [NEIAED]) 3,7-9 has been associated with lower BMD.…”

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confidence: 86%

Antiepileptic drug use and rates of hip bone loss in older men

Ensrud¹,

et al. 2008

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“…34,35,39–47 Only 4 studies included patients aged >65 years. 40,42,44,46 Among the case–control studies, only those by Stephen et al 40 and Lyngstad-Brechan et al 42 included older patients.…”

Section: Resultsmentioning

confidence: 99%

A review of the effect of anticonvulsant medications on bone mineral density and fracture risk

Lee

Lyles

Colón‐Emeric

2010

The American Journal of Geriatric Pharmacotherapy

143

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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.

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“…An unusual observed side effect of "older-generation" AEDs has been their detrimental effects on bone density. In a study by Kubota et al [47], bone density measurements (hip and spine) were performed on 15 epileptic patients aged 20 to 29 years over a 7-year period. The patients were most commonly on phenytoin or phenobarbital.…”

Section: Osteoporosis and Antiepileptic Drugsmentioning

confidence: 99%

Antiepileptic therapy in patients with central nervous system malignancies

Stevens

2006

Curr Neurol Neurosci Rep

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More than 200,000 patients are diagnosed with primary or metastatic brain tumors each year in the United States. Of these patients, 20% to 40% will develop seizures at presentation, and another 20% to 40% will require treatment for seizures during their illness. Although the use of antiepileptic drugs (AEDs) in patients who have had seizures seems reasonable, the issue of prophylactic AED use for patients who have not had a seizure is an intensely debated subject. The American Academy of Neurology released a position statement in May 2000 addressing the use of anticonvulsants in newly diagnosed brain tumor patients who have never had a seizure. After a review of the literature, including all trials showing class I evidence, multivariate analysis using calculated odds ratios failed to show a prophylactic benefit of preventing a first seizure versus the risk of side effects and recommended not using prophylactic anticonvulsants in newly diagnosed patients with brain tumor. Despite this recommendation, a recent survey of the American Association of Neurologic Surgeons revealed that most neurosurgeons still use anticonvulsants prophylactically in patients with brain tumor. This review mainly includes primary brain tumors, but most of the concepts are transferable to patients with metastatic tumors.

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Bone mineral density of epileptic patients on long-term antiepileptic drug therapy: a quantitative digital radiography study

Cited by 38 publications

References 8 publications

Antiepileptic drug use and rates of hip bone loss in older men

Antiepileptic drug use and rates of hip bone loss in older men

A review of the effect of anticonvulsant medications on bone mineral density and fracture risk

Antiepileptic therapy in patients with central nervous system malignancies

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