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.
- Klíčová slova
- Amino-terminal propeptide of procollagen type I, Bone alkaline phosphatase, Bone mineral density, Receptor activator of nuclear factor-kappa B ligand,
- 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
- Názvy látek
- alkalická fosfatasa MeSH
- antikonvulziva MeSH
- gabapentin MeSH
- osteoprotegerin MeSH
- pregabalin MeSH
Taurine, a sulphur - containing amino acid, has been termed a functional nutrient. Its synthetic form is a common ingredient in supplements and energy drinks. There is no information concerning taurine impact on bone microstructure after prolonged supplemental use. Also, differences in bone parameters of mice following taurine exposure are unknown. In this study, a detailed microstructure of compact and trabecular bone tissues of mice subchronically exposed to taurine was determined. Animals (n=12) were segregated into three groups: E1 group - mice received 20 mg/kg b.w. of taurine per day during 8 weeks; E2 group - mice were fed by taurine at a dose of 40 mg/kg b.w. for 8 weeks and a control (C) group. Decreased density of secondary osteons, increased sizes of primary osteon's vascular canals (P<0.05) were observed in taurine - treated animals. Cortical bone thickness, trabecular thickness were decreased (P<0.05) in E1 group, and relative volume of trabecular bone was lower (P<0.05) in E2 group as compared to C group. According to our results, prolonged taurine exposure at the doses used in this study can negatively affect both compact and trabecular bone tissues microstructure.
- MeSH
- femur účinky léků patologie fyziologie MeSH
- kortikální kost cytologie účinky léků fyziologie MeSH
- kostní denzita účinky léků fyziologie MeSH
- myši MeSH
- náhodné rozdělení MeSH
- rozvrh dávkování léků MeSH
- taurin aplikace a dávkování toxicita MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- taurin 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.
- Klíčová slova
- Antiepileptic drugs, Biomechanical properties, Bone markers, Bone mineral density, Levetiracetam,
- 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
- levetiracetam 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
- Názvy látek
- biologické markery MeSH
- levetiracetam MeSH
- piracetam MeSH
Acrylamide (AA) is one of the most common toxins in foods. Its effect on bone microstructure has not been investigated. The aim of our study was to analyze the impact of acute exposure to AA on femoral bone microstructure in mice. Adult animals were treated perorally with 2 doses of AA (E1 group, 1 mg/kg b.w.) in a 24-h period and with 3 doses of AA (E2 group, 1 mg/kg b.w.) in a 48-h period. Mice exposed to AA had smaller sizes of primary osteon's vascular canals. Secondary osteons were significantly smaller in mice from E2 group; however their increased number (from 38 % to 77 %) was identified in both E1 and E2 groups. In these groups, a higher number of resorption lacunae (from 100 % to 122 %) was also found. The values for bone volume, trabecular number were increased and that for trabecular separation was decreased in mice administered AA. Significantly higher value of bone surface was observed in mice from E1 group whereas trabecular thickness was increased in E2 group. The effect of AA on microstructure of compact and trabecular bone tissues is different. In our study, one dose of AA was used and acute effects of AA were investigated. Therefore, further studies are needed to study mechanisms by which AA acts on bone.
- MeSH
- akrylamid toxicita MeSH
- femur diagnostické zobrazování účinky léků patologie MeSH
- kontaminace potravin * MeSH
- kortikální kost diagnostické zobrazování účinky léků patologie MeSH
- myši MeSH
- rentgenová mikrotomografie MeSH
- trabekulární kostní tkáň diagnostické zobrazování účinky léků patologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- akrylamid MeSH
Existing experimental studies of the effect of sympathetic nerve fibers on bone marrow cells are based on the systemic administration of neurotoxic 6-hydroxydopamine. The method of global chemical sympathectomy has some serious disadvantages and could lead to questionable results. We describe a new method of local chemical sympathectomy of rat femoral bone marrow using guanethidine (Ismelin) delivery using an osmotic mini pump. Local guanethidine treatment for 14days led to complete elimination of sympathetic fibers in femoral bone marrow in contrast to bone marrow of contralateral or naïve femurs. Ablation of sympathetic fibers was associated with a loss of rat endothelial cell marker (RECA) indicating immunophenotype changes in blood vessel endothelial cells, but no significant effect of guanethidine was found on the survival of endothelial cells and mesenchymal stem cells in vitro. Moreover, local guanethidine treatment also elicited a significant reduction of Nestin+/SDF1+ mesenchymal stem cells and c-Kit+/CD90+ hematopoietic stem cells in femoral bone marrow. Tissue-specific chemical sympathectomy of rat bone marrow by guanethidine overcomes some of the drawbacks of systemic administration of neurotoxic compounds like 6-hydroxydopamine and delivers unequivocal evidence on the effects of sympathetic innervation on the cell content of bone marrow.
- Klíčová slova
- Endothelial cells, Guanethidine, Osmotic mini pump, Sympathetic innervation,
- MeSH
- endoteliální buňky pupečníkové žíly (lidské) účinky léků metabolismus patologie MeSH
- femur účinky léků inervace metabolismus patologie MeSH
- fluorescenční protilátková technika MeSH
- guanethidin farmakologie MeSH
- kostní dřeň účinky léků inervace metabolismus MeSH
- lidé MeSH
- mezenchymální kmenové buňky účinky léků metabolismus patologie MeSH
- modely u zvířat MeSH
- potkani Wistar MeSH
- průtoková cytometrie MeSH
- sympatektomie chemická MeSH
- sympatický nervový systém účinky léků metabolismus patologie MeSH
- sympatolytika farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- guanethidin MeSH
- sympatolytika 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.
- Klíčová slova
- BALP, Bone mineral density, CTX-I, SNRI, Venlafaxine,
- MeSH
- absorpční fotometrie MeSH
- alkalická fosfatasa metabolismus MeSH
- bederní obratle diagnostické zobrazování účinky léků MeSH
- biologické markery metabolismus MeSH
- biomechanika MeSH
- femur diagnostické zobrazování účinky léků 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
- Názvy látek
- alkalická fosfatasa MeSH
- biologické markery MeSH
- Bmp2 protein, rat MeSH Prohlížeč
- collagen type I trimeric cross-linked peptide MeSH Prohlížeč
- genetické markery MeSH
- inhibitory zpětného vychytávání serotoninu a noradrenalinu MeSH
- kolagen typu I MeSH
- kostní morfogenetické proteiny MeSH
- kostní morfogenetický protein 2 MeSH
- osteoprotegerin MeSH
- peptidové fragmenty MeSH
- peptidy MeSH
- procollagen Type I N-terminal peptide MeSH Prohlížeč
- prokolagen MeSH
- Sost protein, rat MeSH Prohlížeč
- Tnfrsf11b protein, rat MeSH Prohlížeč
- venlafaxin hydrochlorid MeSH
OBJECTIVES: Intake of multivitamin preparations is very common in developed countries. However, excessive intake of vitamin A was associated with increased bone fragility. The aim of this study was to determine if chronic administration of the active metabolite of vitamin A all-trans-retinoic acid (ATRA) in slight excess is associated with changes of bone turnover and density in intact and castrated mice. METHOD: Three mo old male mice (C57B1/6) intact and castrated were injected intraperitonealy with 10 mg/kg/d of the ATRA or vehicle (control) once daily for 3 wk. The bone density, ash weights, calcium, and phosphorus content of the femur were measured. Plasma tartrate-resistant acid phosphatase (Tr-ACP) and serum bone alkaline phosphatase (B-ALP) were determined. RESULTS: ATRA decreased bone density in both groups; however, this effect was more pronounced in castrated animals (1.487 ± 0.04 to 1,360 ± 0.05 g/cm(3)) than in intact mice (1.570 ± 0.03 to 1.510 ± 0.03 g/cm(3)). Bone density correlated with decreased B-ALP and increased Tr-ACP in ATRA-treated mice. ATRA treatment led to significantly lower thickness of cortical bone both in the intact and castrated animals. CONCLUSION: Our results indicate that repeated administration of ATRA in slight excess leads to significant bone loss both in intact and castrated mice. This effect was more pronounced in testosterone-deficient animals. Testosterone deficiency as occurs following castration may sensitize the bone to resorption mediated by ATRA. Therefore, chronic vitamin A administration may be a risk factor for osteoporosis, especially in older and testosterone-depleted subjects.
- Klíčová slova
- All-trans retinoic acid, B-ALP, Bone density, Castration, Tartrate ACP,
- MeSH
- alkalická fosfatasa krev MeSH
- femur chemie účinky léků MeSH
- fosfor krev MeSH
- izoenzymy krev MeSH
- kostní denzita účinky léků MeSH
- kyselá fosfatasa rezistentní k tartarátu MeSH
- kyselá fosfatasa krev MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- orchiektomie MeSH
- osteoporóza chemicky indukované patofyziologie MeSH
- rizikové faktory MeSH
- testosteron krev nedostatek MeSH
- testy toxicity MeSH
- tretinoin aplikace a dávkování toxicita MeSH
- vápník krev MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alkalická fosfatasa MeSH
- fosfor MeSH
- izoenzymy MeSH
- kyselá fosfatasa rezistentní k tartarátu MeSH
- kyselá fosfatasa MeSH
- testosteron MeSH
- tretinoin MeSH
- vápník MeSH
Recent studies have shown that atorvastatin influences bone metabolism. We investigated its bone protective effect in orchidectomised rats after 12 weeks of treatment. Eight-week-old rats were divided into 3 groups: sham-operated group, control group after orchidectomy and experimental group after orchidectomy with atorvastatin administration (12 mg/kg/day). Bone mineral density and bone marker concentrations of aminoterminal propeptide of procollagen type I (PINP), osteoprotegerin (OPG), insulin-like growth factor 1 (IGF-1) in serum, and carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I), bone alkaline phosphatase (BALP), bone morphogenetic protein 2 (BMP-2) in bone homogenate were measured. Total serum calcium and tibial calcium content was determined. Femurs were used for three-point bending test of the shaft and compression testing of the femoral neck. Bone markers (CTX-I, BALP, BMP-2) in control rats were higher vs. sham-operated rats. Atorvastatin reduced CTX-I, BMP-2 and OPG compared to controls. IGF-1 was decreased in control rats vs. sham-operated rats; atorvastatin increased IGF-1 vs. control rats. Atorvastatin exerts a positive effect on bone metabolism by increasing bone mineral density of the whole body, which had decreased under the effects of orchidectomy. Three-point bending test revealed an increase in maximal load values of the left femurs after atorvastatin administration compared to controls. The diameter of the left femur and length of both femurs were increased after atorvastatin administration compared to controls. Our findings suggest that atorvastatin has a beneficial effect on bone metabolism in orchidectomised rats by decreasing bone turnover, with resulting improvement in bone mineral density and bone biomechanical properties.
- MeSH
- atorvastatin MeSH
- biologické markery metabolismus MeSH
- femur účinky léků metabolismus MeSH
- inhibitory kostní resorpce farmakologie terapeutické užití MeSH
- kosti a kostní tkáň metabolismus MeSH
- kostní denzita účinky léků MeSH
- krysa rodu Rattus MeSH
- kyseliny heptylové farmakologie terapeutické užití MeSH
- modely nemocí na zvířatech MeSH
- orchiektomie škodlivé účinky MeSH
- osteoporóza farmakoterapie metabolismus MeSH
- pevnost v tlaku účinky léků MeSH
- potkani Wistar MeSH
- pyrroly farmakologie terapeutické užití MeSH
- tibie účinky léků metabolismus MeSH
- vápník krev metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- atorvastatin MeSH
- biologické markery MeSH
- inhibitory kostní resorpce MeSH
- kyseliny heptylové MeSH
- pyrroly MeSH
- vápník MeSH
Alcohol use has been identified as a risk factor for the development of osteoporosis. Eight male Wistar rats at two months of age were alcoho-fed (7.6 g 95 % ethanol/kg b.w. per day) to evaluate the effects of long-term administration (three months) of alcohol in drinking water. We have used a dose which is considered to be comparable to a dose of 1 liter of wine or 2.5 liters of 12(°) beer used in male adults daily. The bones were tested mechanically by a three-point bending test in a Mini Bionix (MTS) testing system. The bones from alcohol-fed rats were characterized by a reduction in bone density as well as in ash, calcium and phosphate content. In alcohol-fed rats the reduction in bone mineral density (10 %) was reflected by about 12 % reduction of mechanical strength of femur (158+/-5.5 vs. 178+/-3.2 N/mm(2)). Alcohol significantly altered femoral cortical thickness. In our experiment alcohol itself did not exert any antiandrogenic effect and it did not produce changes in the weight of seminal vesicles. Liver function test (GGT, ALP, AST) did not differ between alcohol-fed rats and control rats. Alcohol-induced bone loss is associated with increased bone resorption and decreased bone formation. These results document the efficacy of alcohol at the dose of 7.6 g 95 % ethanol/kg b.w. to cause bone loss and loss of bone mechanical strength in intact rats. The results of the present study may be interpreted as supporting the hypothesis of alcohol as a risk factor for osteoporosis.
- MeSH
- biologické markery krev MeSH
- biomechanika MeSH
- časové faktory MeSH
- enzymy krev MeSH
- ethanol aplikace a dávkování toxicita MeSH
- femur účinky léků metabolismus patologie MeSH
- fosfáty krev MeSH
- jaterní testy MeSH
- játra účinky léků enzymologie MeSH
- kostní denzita účinky léků MeSH
- krysa rodu Rattus MeSH
- osteogeneze účinky léků MeSH
- osteoporóza chemicky indukované metabolismus patologie MeSH
- pití alkoholu škodlivé účinky MeSH
- potkani Wistar MeSH
- resorpce kosti chemicky indukované metabolismus patologie MeSH
- semenné váčky účinky léků MeSH
- vápník krev MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- enzymy MeSH
- ethanol MeSH
- fosfáty MeSH
- vápník MeSH
Raloxifen is a selective estrogen receptor modulator which prevents bone loss in ovariectomized female mice in a fashion similar to estrogens. Since testosterone-deficient male mice also lose bone mass, we were interested in testing the effects of raloxifen on bones in intact and castrated male mice. Bone density was significantly reduced in castrated animals (1.36+/-0.04 g/ml) as compared to intact animals (1.42+/-0.03 g/ml) (p<0.01). When castrated mice with extraordinarily low concentrations of testosterone and with reduced weight of seminal vesicles were treated with raloxifen, the changes in bone density and bone minerals resulting from castration (1.36+/-0.04 g/ml) were entirely prevented (1.40+/-0.01 g/ml). Cortical bone was lost in orchidectomized mice, and this decrease in cortical thickness of the femur was prevented by raloxifen administration. Raloxifen in a dose used in humans for treatment of osteoporosis decreased the weight of seminal vesicles, an organ which is highly sensitive to the androgenic effect, decreased the concentration of testosterone (12.5+/-2.8 micromol/l) (p<0.01) but not to the same level as in the case of castrated animals (0.6+/-0.3 micromol/l), and did not have any effect on bone density or mineral content in intact mice. The results of the present study may thus be interpreted as supporting the hypothesis that raloxifen is an effective agent against the deleterious effects of castration-induced osteopenia in male mice and also support the hypothesis that estrogens may have physiological skeletal effects in male mice.
- MeSH
- femur účinky léků patologie patofyziologie MeSH
- inhibitory kostní resorpce farmakologie terapeutické užití MeSH
- kostní denzita účinky léků MeSH
- metabolické nemoci kostí krev patologie patofyziologie prevence a kontrola MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- orchiektomie * MeSH
- raloxifen hydrochlorid farmakologie terapeutické užití MeSH
- semenné váčky účinky léků patologie MeSH
- testosteron krev MeSH
- velikost orgánu MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- inhibitory kostní resorpce MeSH
- raloxifen hydrochlorid MeSH
- testosteron MeSH