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

Ensrud, Kristine E.; Walczak, Thaddeus S.; Blackwell, Terri; Ensrud, Erik; Barrett‐Connor, Elizabeth; Orwoll, Eric

doi:10.1212/01.wnl.0000324919.86696.a9

Cited by 105 publications

(69 citation statements)

References 36 publications

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“…Another noteworthy study in this arena was a large, community-based study of elderly men in whom bone density was measured twice, an average of 4.6 years apart (17). After adjustment for a large number of potential confounders, those taking inducing AEDs had a rate of bone loss no different from controls, whereas those taking non-inducing AEDs had an accelerated rate of bone loss; in fact, this was larger in patients who were being treated at both time points than in patients who were being treated only at one time point, consistent with a dose-response relationship.…”

Section: Bone and Vitamin D Metabolismmentioning

confidence: 99%

Metabolic consequences of antiepileptic drugs

Mintzer

2010

Current Opinion in Neurology

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Section: Bone and Vitamin D Metabolismmentioning

confidence: 99%

Metabolic consequences of antiepileptic drugs

Mintzer

2010

Current Opinion in Neurology

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“…15) The prospective study showed a significant bone loss in the femoral neck of elderly male patients administered gabapentin. 16) However, the mechanism of the effect of gabapentin on bone metabolism is uncertain and limited data are available with regard to the effects of the new AEDs on bone metabolism. Thus, in the present study, we investigated the effects of phenytoin, gabapentin, and levetiracetam on bone strength, bone mass, and bone turnover in rats.…”

mentioning

confidence: 99%

Effects of the Antiepileptic Drugs Phenytoin, Gabapentin, and Levetiracetam on Bone Strength, Bone Mass, and Bone Turnover in Rats

Kanda

Izumo

Kobayashi

et al. 2017

Biological & Pharmaceutical Bulletin

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Long-term treatment with antiepileptic drugs (AEDs) is accompanied by reduced bone mass that is associated with an increased risk of bone fractures. Although phenytoin has been reported to adversely influence bone metabolism, little is known pertaining to more recent AEDs. The aim of this study was to evaluate the effects of gabapentin or levetiracetam on bone strength, bone mass, and bone turnover in rats. Male Sprague-Dawley rats were orally administered phenytoin (20 mg/kg), gabapentin (30 or 150 mg/kg), or levetiracetam (50 or 200 mg/kg) daily for 12 weeks. Bone histomorphometric analysis of the tibia was performed and femoral bone strength was evaluated using a three-point bending method. Bone mineral density (BMD) of the femur and tibia was measured using quantitative computed tomography. Administration of phenytoin significantly decreased bone strength and BMD, which was associated with enhanced bone resorption. In contrast, treatment with gabapentin (150 mg/kg) significantly decreased bone volume and increased trabecular separation, as shown by bone histomorphometric analysis. Moreover, the bone formation parameters, osteoid volume and mineralizing surface, decreased after gabapentin treatment, whereas the bone resorption parameters, osteoclast surface and number, increased. Levetiracetam treatment did not affect bone strength, bone mass, and bone turnover. Our data suggested that gabapentin induced the rarefaction of cancellous bone, which was associated with decreased bone formation and enhanced bone resorption, and may affect bone strength and BMD after chronic exposure. To prevent the risk of bone fractures, patients prescribed a longterm administration of gabapentin should be regularly monitored for changes in bone mass.Key words gabapentin; levetiracetam; osteoblast; osteoclast; rat Epilepsy is a chronic neurological disorder characterized by recurrent seizures. 1) Pharmacotherapy with antiepileptic drugs (AEDs) is the mainstay of treatment for epilepsy and is effective in the prevention of seizures. Patients with epilepsy usually require long-term treatment with AEDs; thus, the prevention of side effects is important in the continuation of medication.The bone is a metabolically active organ that undergoes continuous remodeling from bone resorption by osteoclasts and bone formation by osteoblasts.2) Under healthy conditions, the balance between bone formation and bone resorption is always uniform; thus, bone strength and bone mass are maintained. Certain pathological states and drugs affect normal bone remodeling, which can induce skeletal disorders, such as osteopenia or osteoporosis.3) A serious side effect associated with long-term administration of AEDs is the elevated risk of bone fracture owing to a decrease in bone mass.4-7) Patients taking AEDs are approximately 2-6 times more at risk of bone fracture than healthy individuals are. 8,9) Previous studies have demonstrated that treatment with phenytoin decreased bone mineral density (BMD) owing to enhanced bone resorption.10,11) Currently, new...

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“…Long-term treatment with AEDs is associated with a facilitated rate of bone loss, and consequently an increased risk of bone fractures (10,19,41). Although topiramate and lamotrigine were approved for clinical use, there are limited data regarding their effects on bone metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…Long-term treatment with antiepileptic drugs (AEDs) has been correlated with bone loss and consequently increased risk of bone fractures (10,19,41). Bone is maintained by continuous remodeling, involving bone formation and bone resorption (31).…”

mentioning

confidence: 99%

<b>Effects of the antiepileptic drugs topiramate and lamotrigine on bone metabolism in </b><b>rats </b>

et al. 2017

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Long-term treatment with antiepileptic drugs (AED) is associated with an elevated risk of bone fracture due to decreased bone mineral density (BMD). Phenytoin has been shown to affect bone metabolism adversely, whereas newly developed AEDs have not been studied. This study evaluated the effects of topiramate and lamotrigine on bone metabolism in rats. Five-week-old male Sprague-Dawley rats were treated orally with phenytoin (20 mg/kg), topiramate (5 or 20 mg/kg), or lamotrigine (2 or 10 mg/kg) daily for 12 weeks. Phenytoin reduced bone strength, measured by maximum load to failure of the femoral mid-diaphysis, along with reduced femur total BMD. Serum tartrate-resistant acid phosphatase-5b levels significantly increased after phenytoin treatment, while serum osteocalcin levels decreased after topiramate 20 mg/kg treatment. Furthermore, osteoblast surface and bone mineralizing surface were significantly lowered by topiramate. Lamotrigine treatment did not affect bone strength, BMD, or bone turnover. We demonstrated that phenytoin treatment significantly increased bone resorption and lowered BMD and bone strength. Since lamotrigine did not affect bone metabolism, it can be concluded that lamotrigine is safety medicine for bone health. Topiramate was associated with decreased bone formation, which may affect bone strength and BMD with chronic use. Thus, patients taking topiramate should be monitored for changes in BMD to avoid risk of fracture.

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

Cited by 105 publications

References 36 publications

Metabolic consequences of antiepileptic drugs

Metabolic consequences of antiepileptic drugs

Effects of the Antiepileptic Drugs Phenytoin, Gabapentin, and Levetiracetam on Bone Strength, Bone Mass, and Bone Turnover in Rats

<b>Effects of the antiepileptic drugs topiramate and lamotrigine on bone metabolism in </b><b>rats </b>

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