Bone turnover markers (BTMs) are released during the bone remodelling cycle and are measurable in blood or urine, reflecting bone remodelling rate. They have been useful in elucidating the pharmacodynamics and effectiveness of osteoporosis medication in clinical trials and are increasingly used in routine clinical management of osteoporosis, especially for monitoring therapy, in addition to their use in other metabolic bone disease such as Paget's disease of bone and osteomalacia. Serum β isomerised C-terminal telopeptide of type I collagen and pro-collagen I N-terminal propeptide have been designated as reference BTMs for use in osteoporosis. In addition, bone-specific isoenzyme of alkaline phosphatase (B-ALP) secreted by osteoblasts and tartrate-resistant acid phosphatase 5b (TRACP-5b) secreted by osteoclasts are also found to be specific markers of bone formation and resorption, respectively. The concentrations of the latter enzymes in blood measured by immunoassay provide reliable measures of bone turnover even in the presence of renal failure. B-ALP is recommended for use in the assessment of renal bone disease of chronic kidney disease, and TRACP-5b shows promise as a marker of bone resorption in that condition. BTMs in blood do not suffer from biological variation to the same extent as the older BTMs that were measured in urine. Appropriate patient preparation and sample handling are important in obtaining accurate measures of BTMs for clinical use. Reference change values and treatment targets have been determined for the reference BTMs for their use in monitoring osteoporosis treatment. Further ongoing studies will enhance their clinical applications.
Some epidemiological studies suggested caffeine consumption as the cause for bone mineral density loss. Certain genes involved in this process are regulated by vitamin D receptor (VDR). Therefore, we investigated if caffeine can affect inducible expression of VDR-regulated genes, some of them being involved in bone mineralization process. By employing reporter gene assay, polymerase chain reaction, and western blotting, we monitored the VDR activity and expression in cell cultures of intestinal (LS180), osteosarcoma (HOS), and normal human osteoblasts in vitro. While caffeine stimulated calcitriol-inducible VDR-dependent nanoluciferase activity in stable reporter cell line IZ-VDRE (derived from LS180), it rather modulated mRNA levels of target genes, like CYP24A1, BGLAP, SPP1, and TNSF11 in LS180 and HOS cells. However, caffeine significantly decreased calcitriol-inducible CYP24A1, TNSF11, and SPP1 transcripts in osteoblasts. This decrease had non-linear U-shaped profile. Our in vitro data demonstrate biphasic action of caffeine on the expression of certain calcitriol-inducible VDR-regulated genes in normal human osteoblasts.
- MeSH
- kalcitriol farmakologie MeSH
- kofein farmakologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- osteoblasty účinky léků metabolismus MeSH
- osteosarkom farmakoterapie metabolismus MeSH
- receptory kalcitriolu účinky léků metabolismus MeSH
- regulace genové exprese účinky léků MeSH
- signální transdukce účinky léků MeSH
- vitamin D metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Good genes, good food, good friends. That is what parents hope will sustain and nurture the harmonious growth of their children. The impact of the genetic background and nutrition on postnatal growth has been in the spot light for long, but the good friends have come to the scene only recently. Among the good friends perhaps the most crucial ones are those that we are carrying within ourselves. They comprise the trillions of microbes that collectively constitute each individual's intestinal microbiota. Indeed, recent epidemiological and field studies in humans, supported by extensive experimental data on animal models, demonstrate a clear role of the intestinal microbiota on their host's juvenile growth, especially under suboptimal nutrient conditions. Genuinely integrative approaches applicable to invertebrate and vertebrate systems combine tools from genetics, developmental biology, microbiology, nutrition, and physiology to reveal how gut microbiota affects growth both positively and negatively, in healthy and pathological conditions. It appears that certain natural or engineered gut microbiota communities can positively impact insulin/IGF-1 and steroid hormone signaling, thus contributing to the host juvenile development and maturation.
- MeSH
- lidé MeSH
- nutriční stav fyziologie MeSH
- potraviny * MeSH
- stárnutí MeSH
- střeva mikrobiologie MeSH
- střevní mikroflóra fyziologie MeSH
- vývojová biologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The transcription factor c-MYB is a well-known marker of undifferentiated cells such as haematopoietic cell precursors, but recently it has also been observed in differentiated cells that produce hard tissues. Our previous findings showed the presence of c-MYB in intramembranous bones and its involvement in the chondrogenic steps of endochondral ossification, where the up-regulation of early chondrogenic markers after c-myb overexpression was observed. Since we previously detected c-MYB in osteoblasts, we aimed to analyse the localisation of c-MYB during later stages of endochondral bone formation and address its function during bone matrix production. c-MYB-positive cells were found in the chondro-osseous junction zone in osteoblasts of trabecular bone as well as deeper in the zone of ossification in cells of spongy bone. To experimentally evaluate the osteogenic potential of c-MYB during endochondral bone formation, micromasses derived from embryonic mouse limb buds were established. Nuclear c-MYB protein expression was observed in long-term micromasses, especially in the areas around nodules. c-myb overexpression induced the expression of osteogenic-related genes such as Bmp2, Comp, Csf2 and Itgb1. Moreover, alizarin red staining and osteocalcin labelling promoted mineralised matrix production in c-myb-overexpressing cultures, whereas downregulation of c-myb by siRNA reduced mineralised matrix production. In conclusion, c-Myb plays a role in the osteogenesis of long bones by inducing osteogenic genes and causing the enhancement of mineral matrix production. This action of the transcription factor c-Myb might be of interest in the future for the establishment of novel approaches to tissue regeneration.
- MeSH
- buněčná diferenciace fyziologie MeSH
- chondrogeneze fyziologie MeSH
- kosti a kostní tkáň metabolismus MeSH
- myši MeSH
- osteoblasty cytologie metabolismus MeSH
- osteogeneze fyziologie MeSH
- osteokalcin metabolismus MeSH
- protoonkogenní proteiny c-myb genetika metabolismus MeSH
- upregulace MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The aim of this study was to investigate the acute effects of oral glucocorticoids in doses used in clinical practice on biochemical indices of the function of osteoclasts, osteoblasts, and osteocytes. In 17 adult patients suffering from various medical pathologies requiring systemic steroid therapy that were never before treated with glucocorticoids, glucocorticoid treatment was initiated (mean prednisolone equivalent dose of 23.1 ± 12.7 mg/day, range 10-50). Fasting morning serum concentrations of osteocalcin (OC), amino-terminal propeptide of type I procollagen (PINP), type 1 collagen cross-linked C-telopeptide (βCTX), soluble receptor activator of nuclear factor kappaB ligand (sRANKL), osteoprotegerin (OPG), sclerostin, Dickkopf-1 (Dkk-1), and high-sensitivity C-reactive protein (hsCRP) were measured at baseline and on three consecutive days. Significant reductions in serum OC, PINP, OPG, sclerostin, and hsCRP were observed during 96 h of glucocorticoid administration, while serum βCTX showed a significant percentual increase. A significant positive correlation was found between serum concentrations of Dkk-1 and βCTX after 96 h of treatment with glucocorticoids. A significant drop in serum sclerostin, OPG, and OC observed in this study may reflect the rapid glucocorticoid-induced apoptosis of osteocytes.
- MeSH
- biologické markery krev MeSH
- C-reaktivní protein metabolismus MeSH
- dospělí MeSH
- genetické markery MeSH
- glukokortikoidy farmakologie terapeutické užití MeSH
- kolagen typu I krev MeSH
- kostní morfogenetické proteiny krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- ligand RANK krev MeSH
- mezibuněčné signální peptidy a proteiny krev MeSH
- osteoblasty účinky léků metabolismus MeSH
- osteocyty účinky léků metabolismus MeSH
- osteokalcin krev MeSH
- osteoklasty účinky léků metabolismus MeSH
- osteoprotegerin krev MeSH
- peptidové fragmenty krev MeSH
- peptidy krev MeSH
- prokolagen krev MeSH
- prospektivní studie MeSH
- revmatické nemoci krev farmakoterapie patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The aim of this study was to calculate rates of hospitalization for hip fracture and the incidence of hip fractures in the Czech Republic over a period of 29 years. A second aim was to use the most recent data to populate a FRAX(®) model for the assessment of fracture probability in individual patients. Data on hospitalizations for hip fracture (1981-2009) and number of women and men with hip fractures (2000-2009) were obtained, and incidences were computed for the entire population ≥50 years of age. Incidence of hospitalization for hip fracture in the Czech population aged ≥50 years increased progressively by calendar year. Age-standardized incidence of hip fractures increased to 2004 but leveled off thereafter and decreased after 2005. Data for hip fracture risk in 2008 and 2009 and the death hazard were used to populate a Czech-specific FRAX model for the computation of 10-year fracture probability. The customized FRAX model, using the verified epidemiological data, will be used to identify patients at increased fracture risk.
- MeSH
- fraktury kyčle epidemiologie etiologie MeSH
- kostní denzita fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- osteoporóza komplikace epidemiologie MeSH
- rizikové faktory MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
The aim of our work was to test the influence of L-carnitine supplementation on secondary hyperparathyroidism and bone metabolism in hemodialyzed patients in a randomized study. Eighty-three chronically hemodialyzed patients were observed; 44 were supplemented with L-carnitine (15 mg/kg intravenously after each hemodialysis for 6 months), while 39 took placebo. Levels of free carnitine (CAR), calcium (Ca), inorganic phosphate (P), Ca x P product, parathormone (PTH), bone-specific alkaline phosphatase (b-ALP), osteocalcin (OC), and osteoprotegerin (OPG) were monitored. In comparison with pretreatment values, changes of some selected parameters occurred in the supplemented patients after 6 months (data are expressed as medians; NS, nonsignificant change): PTH, 186.0 vs. 135.5 ng/L (NS); b-ALP, 13.9 vs. 13.2 microg/L (P < 0.05); OC, 78.3 vs. 68.8 microg/L (NS); OPG, 144.0 vs. 182.0 ng/L (P < 0.05). In the controls, there were the following changes: PTH, 148.0 vs. 207.0 ng/L (NS); b-ALP, 15.2 vs. 13.2 microg/L (P < 0.05); OC, 62.7 vs. 79.8 microg/L (P < 0.05); OPG, 140.0 vs. 164.0 ng/L (NS). A significant correlation was found between CAR and OPG changes (r = 0.51, P < 0.001) in the supplemented patients. The supplementation led to a significant increase of serum OPG concentration. Nevertheless, we observed only nonsignificant tendencies to correction of secondary hyperparathyroidism and reduction of bone turnover in hemodialyzed patients supplemented with L-carnitine in contrast to controls. At this point, the use of L-carnitine does not seem to be justified.
- MeSH
- dialýza ledvin škodlivé účinky MeSH
- financování organizované MeSH
- fosfáty krev MeSH
- karnitin aplikace a dávkování farmakologie MeSH
- kosti a kostní tkáň fyziologie metabolismus účinky léků MeSH
- kostní denzita fyziologie účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- osteokalcin krev účinky léků MeSH
- osteoporóza etiologie farmakoterapie patofyziologie MeSH
- osteoprotegerin krev účinky léků MeSH
- potravní doplňky MeSH
- renální insuficience terapie MeSH
- sekundární hyperparatyreóza etiologie farmakoterapie patofyziologie MeSH
- senioři MeSH
- upregulace fyziologie MeSH
- vápník krev MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- MeSH
- dospělí MeSH
- fraktury spontánní genetika MeSH
- genetická predispozice k nemoci MeSH
- kolagen typu I genetika MeSH
- lidé MeSH
- patní kost metabolismus ultrastruktura MeSH
- polymorfismus genetický MeSH
- postmenopauzální osteoporóza epidemiologie genetika ultrasonografie MeSH
- tělesná hmotnost MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- MeSH
- dospělí MeSH
- finanční podpora výzkumu jako téma MeSH
- kalcitonin krev metabolismus MeSH
- kolagen biosyntéza krev MeSH
- lidé MeSH
- mladiství MeSH
- osteoklasty metabolismus účinky léků MeSH
- resorpce kosti metabolismus MeSH
- tyreoidektomie MeSH
- vápník farmakologie krev MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
