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.
- MeSH
- kosti a kostní tkáň * MeSH
- kostní denzita * MeSH
- krysa rodu rattus MeSH
- orchiektomie MeSH
- potkani Wistar MeSH
- zonisamid farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: There are limited data on the effects of GBP on bone and no data for PGB. Some data suggest that there is a significant influence of sex hormone balance on the susceptibility of bone to antiepileptic drug-induced bone loss. METHODS: Forty-eight male Wistar rats were divided into six groups that were subjected to two surgeries, sham (noORX) or real orchidectomy (ORX), and were fed three diets, a SLD, a SLD enriched with GBP or a SLD enriched with PGB. Dual energy X-ray absorptiometry was used to measure the bone mineral density. The concentrations of bone turnover markers were assayed. The femurs were biomechanically tested. RESULTS: Significant reductions in bone mineral density, weight and biomechanical strength were observed in ORX animals. GBP or PGB exposure did not cause significant alterations in bone mineral density or biomechanical strength. No changes in bone turnover markers were observed, except for RANKL. A significant increase was found in the ORX GBP and ORX PGB groups. Within the orchidectomized animal group, RANKL levels were significantly higher in the ORX PGB group than in the ORX GBP group. CONCLUSIONS: Because neither GBP nor PGB affected bone mineral density or mechanical bone strength, both of these antiepileptic drugs could be considered drugs with lower risks to bone health. A shift in RANKL levels indicates that the effects of GBP and PGB on osteoclast activity may be dependent on the hormonal status of animals.
- MeSH
- absorpční fotometrie metody MeSH
- alkalická fosfatasa metabolismus MeSH
- antikonvulziva farmakologie MeSH
- biomechanika účinky léků MeSH
- femur účinky léků metabolismus MeSH
- gabapentin farmakologie MeSH
- kostní denzita účinky léků MeSH
- krysa rodu rattus MeSH
- orchiektomie metody MeSH
- osteoprotegerin metabolismus MeSH
- potkani Wistar MeSH
- pregabalin farmakologie MeSH
- prospektivní studie MeSH
- remodelace kosti účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
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.
- MeSH
- bederní obratle anatomie a histologie účinky léků metabolismus fyziologie MeSH
- biologické markery metabolismus MeSH
- biomechanika účinky léků MeSH
- femur anatomie a histologie účinky léků metabolismus fyziologie MeSH
- kostní denzita účinky léků MeSH
- krysa rodu rattus MeSH
- piracetam analogy a deriváty farmakologie MeSH
- potkani Wistar MeSH
- tělesná hmotnost účinky léků MeSH
- velikost orgánu účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
OBJECTIVE: Some data suggest that exposure to lamotrigine (LTG) might be associated with impaired bone health in an orchidectomized rat model. The aim of this study was to determine if LTG poses any significant risk for bone in a gonadally intact animals and to compare the effect of LTG with that of phenytoin (PHT). METHOD: Twenty-four rats were divided into control and test groups, (n=8 per group). Control rats received a standard laboratory diet (SDL), while rats in the test groups were fed a SLD enriched with LTG or PHT for 12 weeks. Dual energy X-ray absorptiometry was used to measure bone mineral density (BMD). The concentrations of bone turnover markers (BTM) were assayed in bone homogenates. The femurs were measured and biomechanically tested. RESULTS: Treatment with either LTG or PHT had no significant effect on BMD or on the biomechanical strength of the bones. In contrast to the effect of LTG, we did find significant changes in BTM in the PHT group: a highly significant decrease in the osteoprotegerin/receptor activator of nuclear factor kappa B ratio (p<0.01) and highly significant increases in bone alkaline phosphatase and amino-terminal propeptide of procollagen type I (p<0.001, p˂0.01, respectively). In the LTG group, the only significant change was a decrease in sclerostin (p˂0.05). The PHT level was 19.0 (15.6-19.5) μmol/l, which represents the lower end of the therapeutic range used in humans. The level of LTG was 60.7 (58.5-61.8) μmol/l. CONCLUSIONS: LTG has no effect on the BMD, BTM or mechanical strength in gonadally intact animals. Although a low dose of PHT was associated with enhanced BTM, it did not affect BMD or the biomechanical properties of the bones, similar to the results observed for LTG.
- MeSH
- absorpční fotometrie MeSH
- antikonvulziva farmakologie MeSH
- biologické markery metabolismus MeSH
- biomechanika MeSH
- fenytoin farmakologie MeSH
- kosti a kostní tkáň diagnostické zobrazování účinky léků fyziologie MeSH
- kostní denzita účinky léků fyziologie MeSH
- longitudinální studie MeSH
- potkani Wistar MeSH
- prospektivní studie MeSH
- remodelace kosti účinky léků fyziologie MeSH
- triaziny farmakologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Publikační typ
- abstrakt z konference MeSH
Our goal was to determine if venlafaxine has a negative effect on bone metabolism. Rats were divided into three groups. The sham-operated control group (SHAM), the control group after orchidectomy (ORX), and the experimental group after orchidectomy received venlafaxine (VEN ORX) in standard laboratory diet (SLD) for 12 weeks. Bone mineral content (BMC) was measured by dual energy X-ray absorptiometry (DXA). Bone marker concentrations of carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I), osteoprotegerin (OPG), amino-terminal propeptide of procollagen type I (P1NP), bone alkaline phosphatase (BALP), sclerostin and bone morphogenetic protein 2 (BMP-2) were examined in bone homogenate. The femurs were used for biomechanical testing. Compared to the ORX group we found lower BMD in the diaphysis area of the femur in the VEN ORX group, suggesting a preferential effect on cortical bone. Of the bone metabolism markers, there was significant decrease (ORX control group versus VEN ORX experimental group) in BALP levels and increase in sclerostin and CTX-I levels, suggesting a decrease in osteoid synthesis and increased bone resorption. The results suggest that the prolonged use of venlafaxine may have a negative effect on bone metabolism. Further studies are warranted to establish whether venlafaxine may have a clinically significant adverse effect on bone.
- MeSH
- absorpční fotometrie MeSH
- alkalická fosfatasa metabolismus MeSH
- bederní obratle účinky léků radiografie MeSH
- biologické markery metabolismus MeSH
- biomechanika MeSH
- femur účinky léků radiografie MeSH
- genetické markery MeSH
- inhibitory zpětného vychytávání serotoninu a noradrenalinu toxicita MeSH
- kolagen typu I metabolismus MeSH
- kosti a kostní tkáň účinky léků metabolismus účinky záření MeSH
- kostní denzita účinky léků MeSH
- kostní morfogenetické proteiny metabolismus MeSH
- kostní morfogenetický protein 2 metabolismus MeSH
- lidé MeSH
- orchiektomie * MeSH
- osteoprotegerin metabolismus MeSH
- peptidové fragmenty metabolismus MeSH
- peptidy metabolismus MeSH
- potkani Wistar MeSH
- prokolagen metabolismus MeSH
- remodelace kosti účinky léků MeSH
- tibie účinky léků metabolismus MeSH
- venlafaxin hydrochlorid toxicita MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: Our study aimed to investigate the effect of mirtazapine on bone metabolism in the orchidectomized rat model. METHODS: Rats were divided into three groups. A sham-operated control group (SHAM group) and a control group after orchidectomy (ORX group) received the standard laboratory diet (SLD). An experimental group after orchidectomy (ORX MIRTA group) received SLD enriched with mirtazapine for 12 weeks. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Bone marker concentrations of osteoprotegerin (OPG), amino-terminal propeptide of procollagen type I, bone alkaline phosphatase (BALP), sclerostin and bone morphogenetic protein 2 were examined in bone homogenate. The femurs were used for biomechanical testing. RESULTS: Compared with the control ORX group, we found a lower BMD in the ORX MIRTA group. The differences were statistically significant, although not in the lumbar vertebrae. BMD was lower in the MIRTA group, suggesting a preferential effect on cortical bone. However, although the thickness of the diaphyseal cortical bone was not different, the fragility in the femoral neck area was statistically significantly different between the groups in biomechanical testing. Regarding the bone metabolism markers, there was a significant decrease in OPG and BALP levels, suggesting a reduction in osteoid synthesis. CONCLUSIONS: The results suggest that prolonged use of mirtazapine may have a negative effect on the synthesis of bone and on its mechanical strength, especially in the femoral neck. Further studies are warranted to establish whether mirtazapine may have a clinically significant adverse effect on bone exclusively in the model of gonadectomized rats, or whether the effect occurs also in the model of gonadally intact animals and in respective human models.
- MeSH
- alfa blokátory krev farmakokinetika farmakologie MeSH
- alkalická fosfatasa metabolismus MeSH
- antidepresiva tricyklická krev farmakokinetika farmakologie MeSH
- biomechanika MeSH
- kosti a kostní tkáň účinky léků metabolismus fyziologie MeSH
- kostní denzita účinky léků MeSH
- mianserin analogy a deriváty krev farmakokinetika farmakologie MeSH
- orchiektomie MeSH
- osteoprotegerin metabolismus MeSH
- pevnost v tlaku MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
- MeSH
- absorpční fotometrie MeSH
- acetamidy farmakologie MeSH
- antikonvulziva farmakologie MeSH
- biomechanika MeSH
- epilepsie farmakoterapie metabolismus MeSH
- femur metabolismus MeSH
- kosti a kostní tkáň účinky léků patofyziologie MeSH
- kostní denzita * MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
