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
AN - SCOPUS:85082081749
SN - 1734-1140
VL - 72
SP - 1323
EP - 1333
JO - Pharmacological Reports
JF - Pharmacological Reports
IS - 5
ER -