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Introduction: Our study aimed to investigate the effect of zonisamide (ZNS) on bone metabolism in the rat model. Methods: Eight-week-old rats were divided into four groups. The sham-operated control group (SHAM) and the control group after orchidectomy (ORX) received the standard laboratory diet (SLD). The experimental group after orchidectomy (ORX+ZNS) and the sham-operated control group (SHAM+ZNS) received SLD enriched with ZNS for 12 weeks. Bone marker concentrations in serum of receptor activator of nuclear factor kappa B ligand, PINP, and osteoprotegerin, and the levels of sclerostin and bone alkaline phosphatase in bone homogenate, were measured using an enzyme-linked immunosorbent assay. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. The femurs were used for biomechanical testing. Results: We found a statistically significant reduction in BMD and biomechanical strength 12 weeks after orchidectomy of the rats (ORX). After ZNS administration to orchidectomized rats (ORX+ZNS) and the sham-operated control rats (SHAM+ZNS), there were no statistically significant changes in BMD, bone turnover markers, or biomechanical properties as compared with the ORX group and SHAM group. Conclusions: The results suggest that administration of ZNS to rats exerts no negative effect on BMD, bone metabolism markers, or biomechanical properties. [ABSTRACT FROM AUTHOR]

Aims. While most antiepileptic drugs (AEDs) have been associated with various adverse effects on bone health, for the recently introduced lacosamide (LCM) no corresponding data have been published. The present study evaluates the effect of LCM on bone mineral density, bone turnover markers, and bone mechanical strength in a rat model. Methods. 16 orchidectomized Wistar rats were divided into control and experimental groups, 8 rats each. Dual energy X-ray absorptiometry was used to measure bone mineral density (BMD). As bone metabolism markers, the concentrations of bone markers were assayed in bone homogenate. In addition, both femurs were measured and used for biomechanical testing. Results. Compared to the control group, we found lower BMD in the experimental group in the area of the left (8%) as well as the right femur (12%), all differences being statistically significant. In both femur diaphyses, but not in lumbar vertebrae, BMD was lower in the LCM group, suggesting a preferential effect on cortical bone. However, neither the thickness of the diaphyseal cortical bone nor the fragility in biomechanical testing was different between the groups. Of the bone metabolism markers, the significant decline was in procollagen type I N-terminal peptide (PINP) levels (37.4%), suggesting a decrease in osteoid synthesis. Conclusion: We assume then that long-lasting exposure to LCM can represent a certain risk to the health of bone in the setting of gonadal insufficiency. Further studies will be needed to confirm these findings and to determine how high the risk will be in comparison to the other AEDs. [ABSTRACT FROM AUTHOR]

Some data suggest that exposure to levetiracetam (LEV) might be associated with a risk for bone health in the model of orchidectomized rats. The aim of this study was to investigate if there is any significant risk of LEV for bone health in the model of gonadally intact animals. Wistar rats were divided into a control group and a test group, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed SLD enriched with LEV for 12 weeks. Dual energy X-ray absorptiometry was used to measure BMD of the whole body, femur and lumbar vertebrae. The concentrations of bone markers were examined in bone homogenate. Both femurs and tibiae were used for biomechanical testing. We found in the LEV group significantly decreased absolute and relative values of adipose tissue, higher whole-body BMD, higher right tibia cortical thickness, and a significantly increased concentration of Bone Alkaline Phosphatase (BALP) and cross-linked C-telopeptide of type I collagen (CTX-I) compared with the control group. The results suggest that the long-term administration of LEV in the model of gonadally intact rats does not have a negative effect on bone. Significant increase in BMD and cortical thickness of the right tibia may indicate even a positive influence on the properties of bone. Further studies will be necessary in animals and humans to confirm these findings. [ABSTRACT FROM AUTHOR]

Abstract: There is only limited data concerning the effect of the newer antiepileptic drugs on bone. The objective of this study was to determine the effect of topiramate (TPM) and lamotrigine (LTG) monotherapy on bone mineral density (BMD), mineral content (BMC), bone markers, body composition and bone mechanical strength in the orchidectomized (ORX) rat model. 24 orchidectomized Wistar rats were divided into control and test groups, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed with SLD enriched with LTG or TPM for 12weeks. Dual energy X-ray absorptiometry was used to measure bone mineral density. The concentrations of bone metabolism markers were assayed in bone homogenate. In addition, both femurs were measured and used for biomechanical testing. Compared to the control group, both test groups had significantly lower weight, fat mass, whole body and femur BMD, BMC and reduced mechanical strength of bone. All of these changes were more pronounced in rats exposed to LTG. In conclusion, both LTG and TPM significantly reduce BMD and body weight and impair mechanical strength of bone. A question arises as to the degree of dependence of the effect on the dose. Further studies are warranted to establish whether LTG and TPM may have a clinically significant effect on BMD exclusively in the model of gonadectomized rats, or whether the effect applies also in the model of gonadally intact animals, and in the respective human models. [Copyright &y& Elsevier]

Highlights: [•] Levetiracem is a new antiepileptic drug with uncleat effect on bone. [•] We report here our findings the impact of levetiracetam on bone. [•] We found that long-term LEV treatment significantly reduced BMD and BMC. [ABSTRACT FROM AUTHOR]