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Effects of carbamazepine, eslicarbazepine, valproic acid and levetiracetam on bone microarchitecture in rats

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@article{5868685d71d449dca29a34768fed258f,
title = "Effects of carbamazepine, eslicarbazepine, valproic acid and levetiracetam on bone microarchitecture in rats",
abstract = "BACKGROUND: Metabolic bone disease and fractures are a great problem for patients with epilepsy. The use of antiepileptic drugs (AEDs) is known to play an essential role in the progression of bone loss by various pathophysiological mechanisms. The aim of this study was to evaluate the effects of AEDs on bone microstructure as an additional cause of an increased fracture risk in patients with epilepsy.METHODS: Five groups of each of 12 female rats were orally dosed daily for 8 weeks with either carbamazepine (CBZ) (60 mg/kg), eslicarbazepine (ESL) (80 mg/kg), valproic acid (VPA) (300 mg/kg), levetiracetam (LEV) (50 mg/kg) or saline (control (CTL)). Following killing, dissected femurs were analyzed using X-ray micro-computed tomography (µCT), dual-energy X-ray absorptiometry (DXA) and biomechanical testing. In addition, serum bone turnover markers (BTM) were monitored throughout the experiment.RESULTS: Compared to CTL treatment, VPA decreased bone volume fraction by 19%, decreased apparent density by 14% and increased structural model index by 41%. No changes were observed in bone biomechanics nor mineral density evaluated by DXA or in levels of BTM.CONCLUSIONS: Our findings suggest that VPA affects the microarchitectural properties of the bone. The AEDs CBZ, ESL and LEV appear to have less adverse effects on bone biology and may be a better choice when treating patients with respect to bone health.",
keywords = "Antiepileptic drugs, Fractures, Metabolic bone disease, Microarchitecture, Osteoporosis, Pre-clinical animal model",
author = "Diemar, {Sarah Seberg} and Anne-Sophie Sejling and Pia Eiken and Maria Ellegaard and Ming Ding and Andersen, {No{\'e}mi Becser} and J{\o}rgensen, {Niklas Rye}",
year = "2020",
month = oct,
doi = "10.1007/s43440-020-00087-1",
language = "English",
volume = "72",
pages = "1323--1333",
journal = "Pharmacological Reports",
issn = "1734-1140",
publisher = "Polska Akademia Nauk Instytut Farmakologii",
number = "5",

}

RIS

TY - JOUR

T1 - Effects of carbamazepine, eslicarbazepine, valproic acid and levetiracetam on bone microarchitecture in rats

AU - Diemar, Sarah Seberg

AU - Sejling, Anne-Sophie

AU - Eiken, Pia

AU - Ellegaard, Maria

AU - Ding, Ming

AU - Andersen, Noémi Becser

AU - Jørgensen, Niklas Rye

PY - 2020/10

Y1 - 2020/10

N2 - BACKGROUND: Metabolic bone disease and fractures are a great problem for patients with epilepsy. The use of antiepileptic drugs (AEDs) is known to play an essential role in the progression of bone loss by various pathophysiological mechanisms. The aim of this study was to evaluate the effects of AEDs on bone microstructure as an additional cause of an increased fracture risk in patients with epilepsy.METHODS: Five groups of each of 12 female rats were orally dosed daily for 8 weeks with either carbamazepine (CBZ) (60 mg/kg), eslicarbazepine (ESL) (80 mg/kg), valproic acid (VPA) (300 mg/kg), levetiracetam (LEV) (50 mg/kg) or saline (control (CTL)). Following killing, dissected femurs were analyzed using X-ray micro-computed tomography (µCT), dual-energy X-ray absorptiometry (DXA) and biomechanical testing. In addition, serum bone turnover markers (BTM) were monitored throughout the experiment.RESULTS: Compared to CTL treatment, VPA decreased bone volume fraction by 19%, decreased apparent density by 14% and increased structural model index by 41%. No changes were observed in bone biomechanics nor mineral density evaluated by DXA or in levels of BTM.CONCLUSIONS: Our findings suggest that VPA affects the microarchitectural properties of the bone. The AEDs CBZ, ESL and LEV appear to have less adverse effects on bone biology and may be a better choice when treating patients with respect to bone health.

AB - BACKGROUND: Metabolic bone disease and fractures are a great problem for patients with epilepsy. The use of antiepileptic drugs (AEDs) is known to play an essential role in the progression of bone loss by various pathophysiological mechanisms. The aim of this study was to evaluate the effects of AEDs on bone microstructure as an additional cause of an increased fracture risk in patients with epilepsy.METHODS: Five groups of each of 12 female rats were orally dosed daily for 8 weeks with either carbamazepine (CBZ) (60 mg/kg), eslicarbazepine (ESL) (80 mg/kg), valproic acid (VPA) (300 mg/kg), levetiracetam (LEV) (50 mg/kg) or saline (control (CTL)). Following killing, dissected femurs were analyzed using X-ray micro-computed tomography (µCT), dual-energy X-ray absorptiometry (DXA) and biomechanical testing. In addition, serum bone turnover markers (BTM) were monitored throughout the experiment.RESULTS: Compared to CTL treatment, VPA decreased bone volume fraction by 19%, decreased apparent density by 14% and increased structural model index by 41%. No changes were observed in bone biomechanics nor mineral density evaluated by DXA or in levels of BTM.CONCLUSIONS: Our findings suggest that VPA affects the microarchitectural properties of the bone. The AEDs CBZ, ESL and LEV appear to have less adverse effects on bone biology and may be a better choice when treating patients with respect to bone health.

KW - Antiepileptic drugs

KW - Fractures

KW - Metabolic bone disease

KW - Microarchitecture

KW - Osteoporosis

KW - Pre-clinical animal model

U2 - 10.1007/s43440-020-00087-1

DO - 10.1007/s43440-020-00087-1

M3 - Journal article

C2 - 32193854

VL - 72

SP - 1323

EP - 1333

JO - Pharmacological Reports

JF - Pharmacological Reports

SN - 1734-1140

IS - 5

ER -

ID: 59575939