OBJECTIVES: The primary objective was to determine levels of C3-epi-25(OH)D in very low birth weight infants. The secondary objective was to evaluate the possible influence of preterm birth, intrauterine growth restriction (IUGR), and season of birth on the production of C3-epimers. METHODS: A total of 127 infants with birth weight less than 1,500 g met the inclusion criteria of the study. We examined 25-hydroxyvitamin-D [25(OH)D] levels and C3-epi-25(OH)D in maternal serum before labor, and in cord blood and infants' serum on days 14 and 28, and at discharge. RESULTS: The mean levels (±SD) of C3-epi-25(OH)D of the cord, on day 14, on day 28, and at discharge were 2.2 (2.9), 7.7 (5.5), 11.7 (7.6) and 14.9 (11.7) nmol/L respectively. The proportion of total 25(OH)D as the C3-epimer was 6.9% (cord), 16.3% (day 14), 22.4% (day 28) and 23.3% (discharge). A statistically significant correlation between 25(OH)D and C3-epi-25(OH)D can be demonstrated from birth. The severity of immaturity and IUGR did not affect the production of C3-epimers. In summer/autumn vs. winter/spring, the mean (SD) percentage of total 25(OH)D as the C3-epimer significantly differs only in maternal serum samples and umbilical cord samples (p value <0.001). CONCLUSIONS: The production of C3-epi-25(OH)D is functional even in the most immature newborns, has fetal origins, and is largely dependent on circulating 25(OH)D. At the end of the first month of life, C3-epimers make up more than 20% of 25(OH)D.
- Klíčová slova
- C3-epi-25(OH)D, C3-epimer, newborn, preterm infants, vitamin D,
- MeSH
- kalcifediol MeSH
- kojenec MeSH
- lidé MeSH
- nedostatek vitaminu D * MeSH
- novorozenec nedonošený MeSH
- novorozenec s velmi nízkou porodní hmotností MeSH
- novorozenec MeSH
- předčasný porod * MeSH
- vitamin D MeSH
- vitaminy MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kalcifediol MeSH
- vitamin D MeSH
- vitaminy MeSH
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.
- Klíčová slova
- Antiepileptic drugs, Biomechanical properties, Bone markers, Bone mineral density, Zonisamide,
- 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
- Názvy látek
- zinc sulfide MeSH Prohlížeč
- zonisamid MeSH
PURPOSE: The primary objective of this study was to compare clinical outcomes of very low birth weight (VLBW) infants with 25-hydroxy vitamin D [25(OH)D] levels <25 nmol/l in umbilical cord blood versus VLBW infants with 25(OH)D levels in cord blood >25 nmol/l. The secondary objective was to evaluate umbilical cord vitamin D as a risk factor for respiratory distress syndrome (RDS) in preterm infants. METHODS: We examined 25(OH)D levels in umbilical cord blood and in infants' serum at discharge from the neonatal intensive care unit. We evaluated the associations between severe vitamin D deficiency and various laboratory findings and clinical outcomes. RESULTS: Eighty one infants with birth weight less than 1500 g met the entry criteria for this study and were divided to groups according to umbilical cord blood vitamin D [Group A: 25(OH)D < 25 nmol/l; 10 ng/ml and Group B: 25(OH)D > 25 nmol/l; 10 ng/ml]. Overall, 81.5% of the infants had a 25(OH)D level <50 nmol/L and 44.4% had a level <25 nmol/L. The laboratory findings and the subsequent clinical outcomes were comparable in infants in both groups (non-significant difference). Only the infants in the 25(OH)D 25 nmol/L group had a lower calcium in urine at age 28 d (p=.0272). In addition, we found in this study that umbilical cord vitamin D level does not lead to a higher or lower risk of RDS (odds ratio 1.044; 95% confidence interval 0.349-0.88; p=.0771). CONCLUSIONS: In our prospective cohort study, we found no significant association between vitamin D status and selected clinical outcomes when using a cut-off of 25 nmol/l (severe vitamin D deficiency) in preterm infants.
- Klíčová slova
- 25-hydroxyvitamin D, Vitamin D, clinical outcome, prematurity, preterm infants,
- MeSH
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- nedostatek vitaminu D * komplikace MeSH
- novorozenec nedonošený * MeSH
- novorozenec s velmi nízkou porodní hmotností MeSH
- novorozenec MeSH
- prospektivní studie MeSH
- vitamin D MeSH
- vitaminy MeSH
- Check Tag
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- vitamin D MeSH
- vitaminy MeSH
Purpose: To evaluate vitamin D status in mothers and their very low birth weight infants (VLBW) at birth (umbilical cord blood) and at discharge with currently recommended supplementation of vitamin D.Methods: Ninety-four infants with birth weight less than 1500 g completed the study. The total daily vitamin D intake was 800-1000 IU. We examined 25-hydroxyvitamin-D [25(OH)D] levels in maternal serum before labor, in cord blood, and in infants' serum at discharge.Results: Median (IQR) serum 25(OH)D was 21 (14-36) nmol/l [8 (6-15) ng/ml] in cord blood, and 46 (37-60) nmol/l [18 (15-24) ng/ml] at discharge. Serum 25(OH)D was <50 nmol/L in 71.3% of mothers, in 91.5% of cord blood samples, and in almost 60% of preterm newborns at discharge (after 8 weeks of supplementation). Serum 25(OH)D was <75 nmol/L in 88.3% of mothers, in 97.9% of cord blood samples, and in 91.4% of preterm newborns at discharge.Conclusions: In our cohort, we found that due to the very high prevalence of 25(OH)D deficiency among mothers, the current generally recommended dose of vitamin D (800-1000 IU per day) for VLBW infants was unable to improve vitamin D levels above the desired 50 or even 75 nmol/L before discharge.
- Klíčová slova
- Infants, newborn, preterm, supplementation, vitamin D,
- MeSH
- kojenec MeSH
- lidé MeSH
- nedostatek vitaminu D * farmakoterapie prevence a kontrola MeSH
- novorozenec s velmi nízkou porodní hmotností MeSH
- novorozenec MeSH
- potravní doplňky MeSH
- propuštění pacienta * MeSH
- vitamin D MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- vitamin D 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.
- 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
Purpose: The aim of this pilot study was to estimate physiological parathyroid hormone (PTH) levels and their relationship with bone metabolism parameters in otherwise healthy preterm newborns with birth weight 1000-1500 g. Methods: PTH, 25(OH)D, S-Ca, S-P, and ALP were analysed from blood samples obtained from 20 preterm infants once a week up to the 36th gestational week. Results: Of the total 134 examined serum samples for PTH levels, the estimated range was 1.6-9.3 pmol/l (15.1-87.7 pg/ml). No statistically significant correlation of PTH level with that of S-Ca, S-P, or ALP was observed, except for the 56th day of life (p = .03; Rho = 0.76; n = 8). From the second month of life, there was a statistically significant relationship only between PTH and 25(OH)D (Rho = -0.71, p ≤ .0001). In our cohort, vitamin D deficiency (20 ng/ml) occurred in 75% at birth and at 30% in the 36th gestational week. Conclusions: The physiological range indicated by the measurements was close to the reference limits for adults (1-7 pmol/l; 9.4-66 pg/ml). PTH level above this range can be considered as hyperparathyroidism in preterm neonates.
- Klíčová slova
- Metabolic bone disease, parathyroid hormone, preterm newborn, vitamin D,
- MeSH
- biologické markery krev MeSH
- gestační stáří MeSH
- hyperparatyreóza diagnóza MeSH
- kalcitriol krev MeSH
- kojenec MeSH
- kostní denzita * MeSH
- lidé MeSH
- metabolické nemoci kostí krev diagnóza MeSH
- nedostatek vitaminu D krev diagnóza MeSH
- novorozenec nedonošený MeSH
- novorozenec s extrémně nízkou porodní hmotností MeSH
- novorozenec MeSH
- odběr fetální krve MeSH
- parathormon krev MeSH
- pilotní projekty MeSH
- prospektivní studie MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Názvy látek
- biologické markery MeSH
- kalcitriol MeSH
- parathormon 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
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.
- Klíčová slova
- Amino-terminal propeptide of procollagen type I, Bone alkaline phosphatase, Bone mineral density, Bone turnover markers, Osteoprotegerin/receptor activator of nuclear factor kappa B ratio, Sclerostin,
- 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
- lamotrigin 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
- srovnávací studie MeSH
- Názvy látek
- antikonvulziva MeSH
- biologické markery MeSH
- fenytoin MeSH
- lamotrigin MeSH
- triaziny 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.
- Klíčová slova
- antiepileptic drugs, biomechanical strength, bone markers, bone mineral density, bone turnover,
- 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
- lakosamid 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
- Názvy látek
- acetamidy MeSH
- antikonvulziva MeSH
- lakosamid MeSH
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 12 weeks. 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.
- Klíčová slova
- Antiepileptic drugs, Bone markers, Bone mineral density, Lamotrigine, Topiramate,
- MeSH
- absorpční fotometrie MeSH
- alkalická fosfatasa metabolismus MeSH
- antikonvulziva aplikace a dávkování MeSH
- aplikace orální MeSH
- biomechanika účinky léků MeSH
- ELISA MeSH
- fruktosa analogy a deriváty farmakologie MeSH
- kolagen typu I metabolismus MeSH
- kosti a kostní tkáň účinky léků metabolismus MeSH
- kostní denzita účinky léků MeSH
- kostní morfogenetický protein 2 metabolismus MeSH
- krysa rodu Rattus MeSH
- lamotrigin MeSH
- modely u zvířat MeSH
- neparametrická statistika MeSH
- orchiektomie MeSH
- osteoprotegerin krev MeSH
- peptidové fragmenty metabolismus MeSH
- peptidy metabolismus MeSH
- potkani Wistar MeSH
- prokolagen metabolismus MeSH
- složení těla účinky léků MeSH
- tělesná hmotnost účinky léků MeSH
- topiramat MeSH
- triaziny aplikace a dávkování 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
- alkalická fosfatasa MeSH
- antikonvulziva MeSH
- collagen type I trimeric cross-linked peptide MeSH Prohlížeč
- fruktosa MeSH
- kolagen typu I MeSH
- kostní morfogenetický protein 2 MeSH
- lamotrigin MeSH
- osteoprotegerin MeSH
- peptidové fragmenty MeSH
- peptidy MeSH
- procollagen Type I N-terminal peptide MeSH Prohlížeč
- prokolagen MeSH
- topiramat MeSH
- triaziny MeSH