This study demonstrates the effect of essential fatty acid deficiency on the postnatal skeletal development in the rat. Four groups (n = 10) of newborn Wistar rats were fed diets containing high and low proportions of essential fatty acids in the lipid fraction until day 16 after birth. Suckled littermates were used as controls. X-ray and histological studies showed the occurrence of multiple pathological fractures of the long bones in 1-month-old rats fed a diet deprived of essential fatty acids. No effect of high (51,000 IU/100 g diet) and low (5,100 IU/100 g diet) concentrations of vitamin D2 was observed in our experiment. Thus, these data suggest the importance of essential fatty acids for bone pathology in the rat.

• MeSH
• dietní tuky farmakologie   MeSH
• ergokalciferoly farmakologie   MeSH
• fraktury femuru patologie   MeSH
• fraktury tibie patologie   MeSH
• krysa rodu Rattus MeSH
• mastné kyseliny farmakologie   MeSH
• potkani Wistar MeSH
• vývojové onemocnění kostí patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dietní tuky MeSH
• ergokalciferoly MeSH
• mastné kyseliny MeSH

Due to the aging population, there is an increasing number of fragility fractures of the pelvis (FFP). They are the result of low energy trauma. The bone breaks but the ligaments remain intact. Immobilizing pain at the pubic region or at the sacrum is the main symptom. Conventional radiographs reveal pubic rami fractures, but lesions of the dorsal pelvis are hardly visible and easily overlooked. CT of the pelvis with multiplanar reconstructions show the real extension of the lesion. Most patients have a history of osteoporosis or other fragility fractures. The new classification distinguishes between four categories of different and increasing instability. FFP Type I are anterior lesions only, FFP Type II are non-displaced posterior lesions, FFP Type III are displaced unilateral posterior lesions and FFP Type IV are displaced bilateral posterior lesions. Subgroups discriminate between the localization of the dorsal instability. FFP Type I lesions are treated non-operatively. FFP Type II lesions are fixed in a percutaneous procedure when a trial of conservative treatment was not successful. FFP Type III lesions are treated with open reduction and internal fixation (ORIF). FFP Type IV lesions are treated with bilateral ORIF or with a bridging osteosynthesis. Iliosacral screw osteosynthesis is widely used, but has an elevated risk of screw loosening due to diminished bine mineral density. Transsacral bar osteosynthesis enable interfragmentary compression and does not have this danger of loosening. Bridging plate osteosynthesis is used as an additional fixation to iliosacral screw osteosynthesis. Lumbopelvic fixation is restricted to highly unstable lumbopelvic dissociations. More studies are needed to find the optimal treatment for each type of instability. Key words: pelvis, fragility fracture, diagnosis, classification, treatment.

• MeSH
• fyzioterapie (techniky) MeSH
• inhibitory kostní resorpce terapeutické užití   MeSH
• lidé MeSH
• management bolesti MeSH
• osteoporotické fraktury klasifikace   diagnostické zobrazování   terapie   MeSH
• pánevní kosti zranění   chirurgie   MeSH
• rentgendiagnostika MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vnitřní fixace fraktury metody   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inhibitory kostní resorpce MeSH

Osteoporosis is defined as a systemic skeletal disease characterized by decreased bone mass and micro-architectural deterioration leading to increased fracture risk. Osteoporosis incidence increases with age in both post-menopausal women and aging men. Among other important contributing factors to bone fragility observed in osteoporosis, that also affect the elderly population, are metabolic disturbances observed in obesity and Type 2 Diabetes (T2D). These metabolic complications are associated with impaired bone homeostasis and a higher fracture risk. Expansion of the Bone Marrow Adipose Tissue (BMAT), at the expense of decreased bone formation, is thought to be one of the key pathogenic mechanisms underlying osteoporosis and bone fragility in obesity and T2D. Our review provides a summary of mechanisms behind increased Bone Marrow Adiposity (BMA) during aging and highlights the pre-clinical and clinical studies connecting obesity and T2D, to BMA and bone fragility in aging osteoporotic women and men.

• Klíčová slova
• aging, bone fragility, bone marrow adiposity, obesity, osteoporosis, type 2 diabetes (T2D),
• MeSH
• adipozita MeSH
• diabetes mellitus 2. typu * metabolismus   MeSH
• fraktury kostí * metabolismus   MeSH
• kostní dřeň patologie   MeSH
• lidé MeSH
• obezita metabolismus   MeSH
• osteoporóza * patologie   MeSH
• senioři MeSH
• stárnutí MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Several epidemiological studies have suggested that obesity complicated with insulin resistance and type 2 diabetes exerts deleterious effects on the skeleton. While obesity coexists with estrogen deficiency in postmenopausal women, their combined effects on the skeleton are poorly studied. Thus, we investigated the impact of high-fat diet (HFD) on bone and metabolism of ovariectomized (OVX) female mice (C57BL/6J). OVX or sham operated mice were fed either HFD (60%fat) or normal diet (10%fat) for 12 weeks. HFD-OVX group exhibited pronounced increase in body weight (~86% in HFD and ~122% in HFD-OVX, p < 0.0005) and impaired glucose tolerance. Bone microCT-scanning revealed a pronounced decrease in trabecular bone volume/total volume (BV/TV) (-15.6 ± 0.48% in HFD and -37.5 ± 0.235% in HFD-OVX, p < 0.005) and expansion of bone marrow adipose tissue (BMAT; +60.7 ± 9.9% in HFD vs. +79.5 ± 5.86% in HFD-OVX, p < 0.005). Mechanistically, HFD-OVX treatment led to upregulation of genes markers of senescence, bone resorption, adipogenesis, inflammation, downregulation of gene markers of bone formation and bone development. Similarly, HFD-OVX treatment resulted in significant changes in bone tissue levels of purine/pyrimidine and Glutamate metabolisms, known to play a regulatory role in bone metabolism. Obesity and estrogen deficiency exert combined deleterious effects on bone resulting in accelerated cellular senescence, expansion of BMAT and impaired bone formation leading to decreased bone mass. Our results suggest that obesity may increase bone fragility in postmenopausal women.

• Klíčová slova
• Aging, bone fragility, accelerated aging, bone marrow adiposity, menopause, obesity, osteoporosis, senescence,
• MeSH
• diabetes mellitus 2. typu * komplikace   MeSH
• dieta s vysokým obsahem tuků * škodlivé účinky   MeSH
• estrogeny MeSH
• kosti a kostní tkáň metabolismus   MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• obezita komplikace   metabolismus   MeSH
• ovarektomie škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• estrogeny MeSH

PURPOSE OF REVIEW: The goal of this review is to discuss the role of insulin signaling in bone marrow adipocyte formation, metabolic function, and its contribution to cellular senescence in relation to metabolic bone diseases. RECENT FINDINGS: Insulin signaling is an evolutionally conserved signaling pathway that plays a critical role in the regulation of metabolism and longevity. Bone is an insulin-responsive organ that plays a role in whole body energy metabolism. Metabolic disturbances associated with obesity and type 2 diabetes increase a risk of fragility fractures along with increased bone marrow adiposity. In obesity, there is impaired insulin signaling in peripheral tissues leading to insulin resistance. However, insulin signaling is maintained in bone marrow microenvironment leading to hypermetabolic state of bone marrow stromal (skeletal) stem cells associated with accelerated senescence and accumulation of bone marrow adipocytes in obesity. This review summarizes current findings on insulin signaling in bone marrow adipocytes and bone marrow stromal (skeletal) stem cells and its importance for bone and fat metabolism. Moreover, it points out to the existence of differences between bone marrow and peripheral fat metabolism which may be relevant for developing therapeutic strategies for treatment of metabolic bone diseases.

• Klíčová slova
• Bone marrow adipose tissue, Bone marrow mesenchymal stem cells, Insulin signaling, Marrow adiposity,
• MeSH
• adipogeneze MeSH
• buněčná diferenciace MeSH
• buňky kostní dřeně metabolismus   MeSH
• glukagonu podobný peptid 1 metabolismus   MeSH
• glukosa metabolismus   MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• inzulin metabolismus   MeSH
• inzulinová rezistence MeSH
• kosti a kostní tkáň metabolismus   MeSH
• kostní dřeň metabolismus   MeSH
• lidé MeSH
• metabolické nemoci kostí metabolismus   MeSH
• mezenchymální kmenové buňky metabolismus   MeSH
• obezita metabolismus   MeSH
• parathormon metabolismus   MeSH
• protein 4 vázající insulinu podobné růstové faktory metabolismus   MeSH
• proteiny insulinového receptorového substrátu metabolismus   MeSH
• receptor inzulinu metabolismus   MeSH
• receptor pro konečné produkty pokročilé glykace metabolismus   MeSH
• stárnutí buněk * MeSH
• tuková tkáň metabolismus   MeSH
• tukové buňky metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• glukagonu podobný peptid 1 MeSH
• glukosa MeSH
• insulinu podobný růstový faktor I MeSH
• inzulin MeSH
• parathormon MeSH
• protein 4 vázající insulinu podobné růstové faktory MeSH
• proteiny insulinového receptorového substrátu MeSH
• receptor inzulinu MeSH
• receptor pro konečné produkty pokročilé glykace MeSH

Bone marrow stromal cells (BMSCs) play a significant role in bone metabolism as they can differentiate into osteoblasts, bone marrow adipocytes (BMAds), and chondrocytes. BMSCs chronically exposed to nutrient overload undergo adipogenic programming, resulting in bone marrow adipose tissue (BMAT) formation. BMAT is a fat depot transcriptionally, metabolically, and morphologically distinct from peripheral adipose depots. Reactive oxygen species (ROS) are elevated in obesity and serve as important signals directing BMSC fate. ROS produced by the NADPH oxidase (NOX) family of enzymes, such as NOX4, may be responsible for driving BMSC adipogenesis at the expense of osteogenic differentiation. The dual nature of ROS as both cellular signaling mediators and contributors to oxidative stress complicates their effects on bone metabolism. This review discusses the complex interplay between ROS and BMSC differentiation in the context of metabolic bone diseases.Special attention is paid to the role of NOX4-ROS in regulating cellular processes within the bone marrow microenvironment and potential target in metabolic bone diseases.

• Klíčová slova
• NADPH oxidase, ROS, bone fragility, bone marrow adipose tissue, bone marrow stromal cells, obesity, senescence,
• Publikační typ
• časopisecké články MeSH
• přehledy 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

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
• mirtazapin 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
• Názvy látek
• alfa blokátory MeSH
• alkalická fosfatasa MeSH
• antidepresiva tricyklická MeSH
• mianserin MeSH
• mirtazapin MeSH
• osteoprotegerin MeSH
• Tnfrsf11b protein, rat MeSH Prohlížeč

OBJECTIVE: The use of thiazolidinediones (TZDs) as insulin sensitizers has been shown to have side effects including increased accumulation of bone marrow adipocytes (BMAds) associated with a higher fracture risk and bone loss. A novel TZD analog MSDC-0602K with low affinity to PPARγ has been developed to reduce adverse effects of TZD therapy. However, the effect of MSDC-0602K on bone phenotype and bone marrow mesenchymal stem cells (BM-MSCs) in relation to obesity has not been intensively studied yet. METHODS: Here, we investigated whether 8-week treatment with MSDC-0602K has a less detrimental effect on bone loss and BM-MSC properties in obese mice in comparison to first generation of TZDs, pioglitazone. Bone parameters (bone microstructure, bone marrow adiposity, bone strength) were examined by μCT and 3-point bending test. Primary BM-MSCs were isolated and measured for osteoblast and adipocyte differentiation. Cellular senescence, bioenergetic profiling, nutrient consumption and insulin signaling were also determined. RESULTS: The findings demonstrate that MSDC-0602K improved bone parameters along with increased proportion of smaller BMAds in tibia of obese mice when compared to pioglitazone. Further, primary BM-MSCs isolated from treated mice and human BM-MSCs revealed decreased adipocyte and higher osteoblast differentiation accompanied with less inflammatory and senescent phenotype induced by MSDC-0602K vs. pioglitazone. These changes were further reflected by increased glycolytic activity differently affecting glutamine and glucose cellular metabolism in MSDC-0602K-treated cells compared to pioglitazone, associated with higher osteogenesis. CONCLUSION: Our study provides novel insights into the action of MSDC-0602K in obese mice, characterized by the absence of detrimental effects on bone quality and BM-MSC metabolism when compared to classical TZDs and thus suggesting a potential therapeutical use of MSDC-0602K in both metabolic and bone diseases.

• Klíčová slova
• Bone marrow adiposity, Bone marrow mesenchymal stem cells, Bone microstructure, Obesity-induced bone fragility, Pioglitazone, Thiazolidinedione analog MSDC-0602K,
• MeSH
• antigen stromálních buněk kostní dřeně metabolismus   farmakologie   MeSH
• glukosa metabolismus   MeSH
• glutamin metabolismus   MeSH
• hypoglykemika farmakologie   MeSH
• inzulin metabolismus   MeSH
• lidé MeSH
• mezenchymální kmenové buňky * metabolismus   MeSH
• myši obézní MeSH
• myši MeSH
• obezita farmakoterapie   metabolismus   MeSH
• pioglitazon metabolismus   farmakologie   MeSH
• PPAR gama metabolismus   MeSH
• spirosloučeniny MeSH
• thiazolidindiony * farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 10-methyl spiro(4.5)dec-6-en-6-carboxylic acid MeSH Prohlížeč
• 2,4-thiazolidinedione MeSH Prohlížeč
• antigen stromálních buněk kostní dřeně MeSH
• glukosa MeSH
• glutamin MeSH
• hypoglykemika MeSH
• inzulin MeSH
• pioglitazon MeSH
• PPAR gama MeSH
• spirosloučeniny MeSH
• thiazolidindiony * MeSH

Cortical bone plays a vital role in determining overall bone strength. We investigate the structural, compositional, and nanomechanical properties of cortical bone following ovariectomy (OVX) of 12-week-old Sprague Dawley rats, since this animal model is frequently employed to evaluate the performance of implantable biomaterials in compromised bone healing conditions. Morphological parameters and material properties of bone in the geometrical center of the femoral cortex were investigated four and eight weeks post-OVX and in unoperated controls (Ctrl), using X-ray micro-computed tomography, backscattered electron scanning electron microscopy, Raman spectroscopy, and nanoindentation. The OVX animals showed increase in body weight, diminished bone mineral density, increased intracortical porosity, but increased bone mass through periosteal apposition (e.g., increases in periosteal perimeter, cortical cross-sectional thickness, and cross-sectional area). However, osteocyte densities, osteocyte lacunar dimensions, and the nanomechanical behavior on the single mineralized collagen fibril level remained unaffected. Our correlative multiscale investigation provides structural, chemical, and nanomechanical evidence substantiating earlier reports suggesting that rats ovariectomized at 12 weeks undergo simultaneous bone loss and growth, resulting in the effects of OVX being less obvious. Periosteal apposition contradicts the conventional view of bone loss in osteoporosis but appears advantageous for the greater functional demand imposed on the skeleton by increased body weight and fragility induced by increased intracortical porosity. Through a variety of morphological changes, it is likely that 12-week-old rats are able to adapt to OVX-related microstructural and compositional alterations. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 997-1007, 2018.

• Klíčová slova
• Raman spectroscopy, bone, nanoindentation, osteoporosis, ovariectomy,
• MeSH
• biomechanika MeSH
• extracelulární matrix metabolismus   MeSH
• femur patologie   patofyziologie   MeSH
• kortikální kost diagnostické zobrazování   patologie   patofyziologie   MeSH
• lineární modely MeSH
• minerály metabolismus   MeSH
• nanočástice chemie   MeSH
• osteocyty metabolismus   MeSH
• osteoporóza diagnostické zobrazování   patologie   patofyziologie   MeSH
• počet buněk MeSH
• poréznost MeSH
• potkani Sprague-Dawley MeSH
• rentgenová mikrotomografie MeSH
• tělesná hmotnost MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• minerály MeSH