Effects of carbamazepine, eslicarbazepine, valproic acid and levetiracetam on bone microarchitecture in rats
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ARTICLE
Effects of carbamazepine, eslicarbazepine, valproic acid and levetiracetam on bone microarchitecture in rats Sarah Seberg Diemar1,2 · Anne‑Sophie Sejling3 · Pia Eiken3 · Maria Ellegaard4 · Ming Ding2,5 · Noémi Becser Andersen1 · Niklas Rye Jørgensen2,4 Received: 8 November 2019 / Revised: 24 February 2020 / Accepted: 9 March 2020 © Maj Institute of Pharmacology Polish Academy of Sciences 2020
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 Pre-clinical animal model · Antiepileptic drugs · Metabolic bone disease · Fractures · Microarchitecture · Osteoporosis
* Sarah Seberg Diemar [email protected] 1
Epilepsy Unit, Department of Neurology, Rigshospitalet Glostrup, Valdemar Hansens vej 13, 6th floor, 2600 Glostrup, Denmark
2
OPEN, Open Patient Data Explorative Network, Odense University Hospital/Institute of Clinical Research, University of Southern Denmark, J. B. Winsløws vej 19, 5000 Odense C, Denmark
3
Department of Endocrinology and Nephrology, Nordsjællands Hospital, Dyrehavevej 29, 3400 Hillerød, Denmark
4
Department of Clinical Biochemistry, Rigshospitalet Glostrup, Valdemar Hansens vej 1‑23, 2600 Glostrup, Denmark
5
Orthopaedic Research Laboratory, Department of Orthopaedic Surgery and Traumatology, Odense University Hospital/Institute of Clinical Research, University of Southern Denmark, J. B. Winsløws vej 4, 5000 Odense C, Denmark
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Introduction Patients with epilepsy have an increased risk of developing metabolic bone disease and have up to six times increased fracture risk [1–4]. Osteoporosis and subsequent fractures have great consequences fo
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