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

Abstract

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.

Adverse Metabolic Effects of Antiepileptic Drug Treatment

“…Accumulating evidence indicates an association between long-term use of AEDs and disturbed bone metabolism, resulting in decreased bone mineral density (BMD) and an increased risk of fractures (Lee, 2010). This is particularly problematic for people with epilepsy as their propensity to fractures is already elevated due to other drug side-effects (e.g.…”

“…Further, there are no formal guidelines for monitoring, prevention, and management of bone disease among those patients using AEDs (Lee, 2010). However, those AEDs that involve the CYP450 enzyme system should be avoided, if possible, in high risk patients (Table 1).…”

Metabolic bone disorders in children with epilepsy

“…Inadequate levels of calcium and vitamin D lead to the softening of the bone and the impairment of bone mineralization. The final result is the manifestation of clinical osteomalacia [22], while vitamin D supplementation can increase the bone mineral content [23]. Vitamin D receptor contains two sites for ligand binding, the genomic pocket which is responsible for gene transcription and the alternative pocket which acts for direct rapid responses.…”

Systemic Lupus Erythematosus, Osteoporosis, and Fractures

“…Other drugs that are associated with fractures and may be used in the SLE population include anticonvulsants 10 , and benzodiazepines 17 . confound the bone loss seen in SLE.…”

“…In those with neuropsychiatric SLE, there is an increased risk 3 . In addition to seizures, the use of anticonvulsants may be associated with fractures 10 .…”