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Objective:Based on Web of Science database, this study aimed to explore the current status, research hotspots and development trends of countries regarding clinical management of osteoporotic fractures using bibliometrics and visualized analysis.Methods:We collected literatures in the field of clinical management of osteoporotic fractures included in Web of Science database, and applied bibliometrics to analyze the publication dates, countries, institutions, journals, authors, highly cited literatures and research hotspots. Visualization was drawn by VOSviewer software.Results:Analysis of the 2 508 articles revealed 3 types of data. (1) The analysis of basic information of the literature showed that: ①The country with the largest number of publications was the United States, which published 672 articles, followed by the United Kingdom and Canada, and China ranked fourth; ②The top three authors in the number of publications were Kanis JA, Cooper C and McCloskey EV respectively; ③The institution with the highest number of publications was the University of Sheffield, UK, followed by the University of Southampton, UK and the University of Toronto, Canada. (2) Network visualization of highly cited literatures showed that 118 highly cited literatures were mainly divided into 5 clusters, which were related to osteoporotic fracture diagnosis, treatment, medication adherence, management consensus and strategies of preventing refracture. (3) Temporal overlay visualization of research hotspots showed that early research mainly focused on traditional therapeutic drugs, and current research hotspots were mainly molecular targeted drugs, trabecular bone score and fracture liaison services.Conclusion:This study shows that the research activity of clinical management of osteoporotic fractures is increasing worldwide, and there is still a huge gap between China and Europe or the United States. Current research hotspots and development trends mainly focus on molecular targeted drugs, osteoporotic fracture treatment concepts, emerging fracture risk assessment tools, and fracture prevention and management models.
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Objective:To explore the changes of bone mineral density (BMD) and type H vessel, which was recently identified as strongly positive for CD31 and Endomucin (CD31 hiEmcn hi) in long bone from ovariectomized (OVX) mice compared withSham group. Methods:C57BL/6Jwild-type mice were used for experiments and bone tissuewas collected. Eight-week-old female mice were randomly divided into bilateral ovariectomy (OVX) and a sham operation (Sham). The bilateral ovaries were exposed and removed in the OVX group. In the sham group, the ovaries were only exposed but left intact. After 4weeks, these mice were killed for experiment and the femurs were collected for Micro CT scanning in order to observe the changes of bone mineral density (BMD) and trabecular indexes, including bone volume (BV), total volume of interest (TV), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number (Tb.N). The fresh tibia of each mouse was fixed, decalcified, dehydrated and embedded for immunostaining. All experimental data were analyzed with t-test. Results:Mouse femora from two groups were dissected at 4 week time points, and the attached soft tissue was completely removed for Micro CT scanning. BMD in OVX is 0.11±0.01 g/cm 3 and 0.21±0.01 g/cm 3 in Sham, which indicated the BMD in OVX significantly decreased. The results showed significant difference between the groups ( P=0.001). The microarchitecture in trabecular bone changed. BV/TV in OVX is 11.52%±1.77% and 25.87%±1.31% in Sham, which indicated the BV/TV in OVX significantly decreased. The results showed significant difference between the groups ( P<0.05). Tb.N in OVX is 1.67±0.33/mm and 2.95±0.82/mm in Sham, which indicated the Tb.N in OVX slightly decreased. The results showed no significant difference between the groups ( P=0.066). Tb.Th in OVX is 0.06±0.01 mm and 0.07±0.01 mm in Sham, which indicated the Tb.Th in OVX significantly thinned. The results showed significant difference between the groups ( P=0.021). Tb.Sp in OVX is 0.29±0.15 mm and 0.19±0.01 mm in Sham, which indicated the Tb.Sp in OVX significantly increased. The results showed significant difference between the groups ( P<0.05). In the groups BMD decreased and trabecular microstructure was broken. Both BMD and trabecular indexes (BV/TV, Tb. Th, Tb. Sp) showed significant changes in OVX group compared with Sham ( P<0.05) except Tb.N. We next examined the expression of CD31 and EMCN via immunostaining in order to observe the changes of type H vessel.By immunostaining, the percentage of HV/TV in OVX group was 9.14%±0.99% and 29.33%±1.22% in the sham-operated mice. Dramatically decreased type H vessels in the metaphysis of OVX mice were observed compared with that of Sham control mice. The results showed significant difference between the groups ( P<0.05). Conclusion:In this study, ovariectomized mice, a widely used model for postmenopausal osteoporosis, exhibited significantly reduced type H vessels accompanied by reduced BMD, which indicatedtype H vessel involved in the occurrence of postmenopausal osteoporosis.
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Objective@#To investigate the effect of endogenous iron accumulation onbone mass, intraosseous vessels and the effect of exogenous iron on endothelial cell activity.@*Methods@#The mice were divided into control group (C57/BL6 mice without hepcidin knockout) and hepcidin-knockout group (10 mice in each group, 8 weeks old and weighing about 22 g). The mice in both groups were killed at the age of 16 weeks. Serum ferritin levels were measured by Enzyme-linked immunosorbent assay (ELISA), and iron accumulation in liver tissue was measured by Prussian blue staining, while femoral micro-structure was measured by micro-CT, and H-type vessel immunofluorescence staining was used to detect the number of H-vessels in bone. Cell experiments were divided into normal culture group (normal cell group) and intervention group (Fe group) with 200 μmol/L ammonium ferric citrate. Scratch test was used to detect the migration ability of vascular endothelial cells, and tube formation test was used to detect the function of vascular endothelial cells. The endothelial activity of vascular endothelial cells was detected by immunofluorescence.@*Results@#The level of serum ferritin (318.30±12.53 ng/ml) in the hepcidin-knockout group was significantly higher than that in control group (109.60±4.66 ng/ml). The percentage of blue area of Prussian liver iron staining in the hepcidin-knockout group (80.80%±3.156%) was significantly higher than that in control group (20.94%±2.813%). Bone mineral density in the hepcidin-knockout group (0.044±0.002 mg/m3) was significantly higher than that in control group (0.131±0.008 mg/m3). The number of intraosseous blood vessels in the hepcidin-depleted mice (17.06%±1.060%) was significantly lower than that in control group (38.76%±4.576%). There were significant differences between the two groups in each index (t=-49.367,-13.788, 35.293, 6.165; all P < 0.05). The scratches of vascular endothelial cells in Fe group were reduced by 24.300%±1.849% after 24 hours of culture, which was significantly lower than that in normal group (39.060%±3.211%). The area of vascular endothelial cells in Fe group (0.035±0.003 mm2) was significantly lower than that in normal group (0.330±0.018 mm2). The EMCN positive cells of vascular endothelial cells in Fe group were significantly lower than those in normal group. The percentage of cell number (12.000%±3.462%) was significantly lower than that of normal cell group (0.035%±0.003%). There were significant differences in cell indices between the two groups (t=9.790, 18.929, 13.922; all P< 0.05).@*Conclusion@#Endogenous iron accumulation aggravated bone loss in mice, and the number of intraosseous blood vessels decreased significantly. Vascular endothelial cells were inhibited by iron intervention in migration, tube-formation and endothelial ability.
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The specimens of femur from wild-type mice(WT) of 6 months and Hepcidin-knockout(KO) mice of 6 months(iron accumulation model) were obtained for Micro-CT examination. Western blot and co-immunoprecipitation were used to detect the changes of related parameters in Wnt signaling pathway. Compared with wild-type mice, the bone mass in Hepcidin-KO mice was significantly decreased, the binding of β-catenin to FOXO3a increased, and binding of β-catenin to TCF4/TCF7L2 decreased in bone tissue, without significant changes in the expression of β-catenin, TCF4/TCF7L2, and FOXO3a. These results suggest that iron accumulation may affect bone formation through interfering with canonical Wnt/β-catenin signaling pathway, finally leading to osteoporosis.
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The specimens of femur from wild-type mice(WT) of 6 months and Hepcidin-knockout(KO) mice of 6 months ( iron accumulation model ) were obtained for Micro-CT examination. Western blot and co-immunoprecipitation were used to detect the changes of related parameters in Wnt signaling pathway. Compared with wild-type mice, the bone mass in Hepcidin-KO mice was significantly decreased, the binding ofβ-catenin to FOXO3a increased, and binding of β-catenin to TCF4/TCF7L2 decreased in bone tissue, without significant changes in the expression ofβ-catenin, TCF4/TCF7L2, and FOXO3a. These results suggest that iron accumulation may affect bone formation through interfering with canonical Wnt/β-catenin signaling pathway, finally leading to osteoporosis.[Summary] The specimens of femur from wild-type mice(WT) of 6 months and Hepcidin-knockout(KO) mice of 6 months ( iron accumulation model ) were obtained for Micro-CT examination. Western blot and co-immunoprecipitation were used to detect the changes of related parameters in Wnt signaling pathway. Compared with wild-type mice, the bone mass in Hepcidin-KO mice was significantly decreased, the binding ofβ-catenin to FOXO3a increased, and binding of β-catenin to TCF4/TCF7L2 decreased in bone tissue, without significant changes in the expression ofβ-catenin, TCF4/TCF7L2, and FOXO3a. These results suggest that iron accumulation may affect bone formation through interfering with canonical Wnt/β-catenin signaling pathway, finally leading to osteoporosis.
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Objective To investigate the effect of endogenous iron accumulation onbone mass, intraosseous vessels and the effect of exogenous iron on endothelial cell activity. Methods The mice were divided into control group (C57/BL6 mice with?out hepcidin knockout) and hepcidin?knockout group (10 mice in each group, 8 weeks old and weighing about 22 g). The mice in both groups were killed at the age of 16 weeks. Serum ferritin levels were measured by Enzyme?linked immunosorbent assay (ELI?SA), and iron accumulation in liver tissue was measured by Prussian blue staining, while femoral micro?structure was measured by micro?CT, and H?type vessel immunofluorescence staining was used to detect the number of H?vessels in bone. Cell experiments were divided into normal culture group (normal cell group) and intervention group (Fe group) with 200 μmol/L ammonium ferric ci?trate. Scratch test was used to detect the migration ability of vascular endothelial cells, and tube formation test was used to detect the function of vascular endothelial cells. The endothelial activity of vascular endothelial cells was detected by immunofluores?cence. Results The level of serum ferritin (318.30±12.53 ng/ml) in the hepcidin?knockout group was significantly higher than that in control group (109.60±4.66 ng/ml). The percentage of blue area of Prussian liver iron staining in the hepcidin?knockout group (80.80%±3.156%) was significantly higher than that in control group (20.94%±2.813%). Bone mineral density in the hepci? din?knockout group (0.044±0.002 mg/m3) was significantly higher than that in control group (0.131±0.008 mg/m3). The number of intraosseous blood vessels in the hepcidin?depleted mice (17.06% ± 1.060% ) was significantly lower than that in control group (38.76%±4.576%). There were significant differences between the two groups in each index (t=-49.367,-13.788, 35.293, 6.165;all P<0.05). The scratches of vascular endothelial cells in Fe group were reduced by 24.300%±1.849% after 24 hours of culture, which was significantly lower than that in normal group (39.060%±3.211%). The area of vascular endothelial cells in Fe group (0.035±0.003 mm2) was significantly lower than that in normal group (0.330±0.018 mm2). The EMCN positive cells of vascular en?dothelial cells in Fe group were significantly lower than those in normal group. The percentage of cell number (12.000%±3.462%) was significantly lower than that of normal cell group (0.035%±0.003%). There were significant differences in cell indices between the two groups (t=9.790, 18.929, 13.922; all P<0.05). Conclusion Endogenous iron accumulation aggravated bone loss in mice, and the number of intraosseous blood vessels decreased significantly. Vascular endothelial cells were inhibited by iron interven?tion in migration, tube?formation and endothelial ability.
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Objective To explore the infiltration and apoptosis of eosinophilia(EOS)and the influence of death receptor(Fas) and B cell lymphoma-2 (Bcl-2) expression after Belamcanda and Ephedra Decoction on asthma rats.Methods40 healthy rats of Holland were selected as the research subjects,they were divided into four groups: control group,asthma model group, dexamethasone group,Belamcanda and Ephedra Decoction group with 10 rats in each group.Rat asthma model was prepared by repeated stimulation of egg protein,the symptoms of asthma in each group were evaluated;the number of EOS infiltration in lung tissue was detected by staining method;EOS apoptosis was detected by methyl thiazolyl tetrazolium(MTT) method;Blot Western was used to detect the expression of Fas and Bcl-2 protein;the flow cytometry was used to detect the apoptosis of EOS in rat.ResultsCompared with the rats in the model group, dexamethasone group, Belamcanda and Ephedra Decoction group rats asthma symptoms were significantly reduced, scores were significantly lower (P< 0.05),there was no significant difference between Dexamethasone group and sheganmahuang Decoction group.In the asthma model group,the number of EOS infiltration and EOS% in venous blood and lung tissue were significantly higher than those in control group,EOS apoptosis rate was significantly lower than that of the control group (P< 0.05).In Dexamethasone group,Belamcanda and Ephedra Decoction group infiltration number of EOS and EOS% were significantly lower than that of model group but higher than the control group, the apoptosis rate of EOS protein was significantly higher than the model group and the control group (P< 0.05),there was no significant difference between Dexamethasone group and sheganmahuang Decoction group.The expression of Fas in dexamethasone group,Belamcanda and Ephedra Decoction group was significantly higher than the control group and model group (P< 0.05),Bcl-2 protein was significantly lower than the control group and model group (P< 0.05),there was no significant difference between Dexamethasone group and sheganmahuang Decoction group.Cell flow cytometry showed that the control group had no cell apoptosis,a large number of apoptotic cells were appeared after Belamcanda and Ephedra Decoction treat with.ConclusionBelamcanda and Ephedra decoction can induce apoptosis of EOS expression,it may be associated with the upregulation of Fas, downregulation of Bcl-2 expression.
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Objective To explore the changes of type H vessel during the low bone mineral density caused by iron accumulation and discuss its clinical meaning.Methods Ten 8-week old male C57BL/6J mice were used for experiments,and randomly divided into two groups:control group and iron group,and 5 mice in each group.In the iron group,0.1 g/kg of iron dextran was injected intraperitoneally once a week for 8 weeks.The control group was injected with the same amount of saline.The femoral and tibial specimens were examined by microscopic CT scan and bone tissue type H vessel immunohistochemical staining.Liver tissue from the two groups were collected for the content of iron by atomic absorption spectroscopy.All experimental data were analyzed with t-test.Results The content of hepatic iron in mice was significantly higher than that in the control group,which indicating that the model was successfully established.The tibia specimens were collected for immunostaining.The vascular area of type H at metaphyseal regions is 11.24％± 1.76％ in iron group and 30.69％±2.78％ in control group,respectively.There is significant difference between the two groups (P＜0.005).The femur specimens were collected for Micro-CT scan,the value of bone mineral density (BMD),bone volume/tissue volume (BV/TV),trabecular thickness (Tb.Th),trabecular number (Tb.N) and trabecular separation (Tb.Sp) was (0.19±0.013) g/cm3,11.92％±1.199％,(35.66±2.684) μm,(2.36±0.429)/mm and (284.41±23.197) μm in iron group and (0.37±0.023) g/cm3,35.76％± 1.336％,(62.05±2.238) μm,(5.68± 1.039)/mm and (163.23± 13.203) μm in control group,respectively.The differences between the two groups were statistically significant (P＜0.05).Conclusion Iron accumulation can lead to low BMD and suppress type H vessel formation in bone,which might provide a new experimental value for mechanism research on osteoporosis caused by iron accumulation.