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Role of Sclerostin in the Bone Loss of Postmenopausal Chinese Women with Type 2 Diabetes 被引量:16
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作者 Yi-jun Zhou Ai Li +3 位作者 Yu-ling Song Hui Zhou Yan Li Yin-si Tang 《Chinese Medical Sciences Journal》 CAS CSCD 2013年第3期135-139,共5页
Objective To evaluate the role of sclerostin in bone loss of postmenopausal Chinese women with type 2 diabetes me|litus. Methods The postmenopausal patients suffering from type 2 diabetes mellitus and age, body mass... Objective To evaluate the role of sclerostin in bone loss of postmenopausal Chinese women with type 2 diabetes me|litus. Methods The postmenopausal patients suffering from type 2 diabetes mellitus and age, body mass index, and duration of menopause matched healthy controls were enrolled into this cross-sectional study according to criteria of inclusion and exclusion. 展开更多
关键词 sclerostin type 2 diabetes mellitus postmenopausE bone markers bone mineral density
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Calcium-fortified fresh milk ameliorates postmenopausal osteoporosis via regulation of bone metabolism and gut microbiota in ovariectomized rats 被引量:1
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作者 Qishan Wang Bin Liu +5 位作者 Xianping Li Junying Zhao Zongshen Zhang Weicang Qiao Xinyue Wei Lijun Chen 《Food Science and Human Wellness》 SCIE CSCD 2024年第3期1258-1270,共13页
The aging of the global population has made postmenopausal osteoporosis prevention essential;however,pharmacological treatments are limited.Herein,we evaluate the effect of calcium-fortified fresh milk(FM)in ameliorat... The aging of the global population has made postmenopausal osteoporosis prevention essential;however,pharmacological treatments are limited.Herein,we evaluate the effect of calcium-fortified fresh milk(FM)in ameliorating postmenopausal osteoporosis in a rat model established using bilateral ovariectomy.After 3 months of FM(containing vitamin D,and casein phosphopeptides,1000 mg Ca/100 g)or control milk(110 mg Ca/100 g milk)supplementation,bone changes were assessed using dual-energy X-ray absorptiometry,microcomputed tomography,and bone biomechanical testing.The results revealed that FM can regulate bone metabolism and gut microbiota composition,which act on bone metabolism through pathways associated with steroid hormone biosynthesis,relaxin signaling,serotonergic synapse,and unsaturated fatty acid biosynthesis.Furthermore,FM administration significantly increased bone mineral content and density in the lumbar spine and femur,as well as femoral compressive strength,while improving femoral trabecular bone parameters and microarchitecture.Mechanistically,we found that the effects may be due to increased levels of estrogen,bone formation marker osteocalcin,and procollagen typeⅠN-propeptide,and decreased expression of the bone resorption marker C-telopiptide and tartrate-resistant acid phosphatase 5b.Overall,the findings suggest that FM is a potential alternative therapeutic option for ameliorating postmenopausal osteoporosis. 展开更多
关键词 Dairy products CALCIUM Vitamin D Bone turnover markers Gut microbiota postmenopausal osteoporosis
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Research trends in exercise therapy for the treatment of pain in postmenopausal osteoporosis over the past decade:A bibliometric analysis
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作者 Zhao-Qiu Dai Xiao-Yan Gong +8 位作者 Rong Zhang Mei-Qin Jin Wei Lu Wen Wen Jie Chen Fang-Jie Lu Yi-Fan Yang Lei Wang Xiao-Jin He 《World Journal of Orthopedics》 2024年第10期950-964,共15页
BACKGROUND Postmenopausal osteoporosis(PMOP)is the most common form of primary osteoporosis among women,and the associated pain often drives patients to seek clinical intervention.Numerous studies have highlighted the... BACKGROUND Postmenopausal osteoporosis(PMOP)is the most common form of primary osteoporosis among women,and the associated pain often drives patients to seek clinical intervention.Numerous studies have highlighted the unique clinical benefits of exercise therapy(ET)in alleviating PMOP-related pain.However,bibliometric analyses examining collaboration,development trends,and research frontiers in the field of ET for PMOP pain remain scarce.AIM To explore the research trends in ET for pain treatment in PMOP patients over the past decade.METHODS All scholarly works were meticulously sourced from the Science Citation Index-Expanded within the prominent Web of Science Core Collection.Utilizing the capabilities of CiteSpace 6.2.R5,we conducted a thorough analysis of publications,authors,frequently cited scholars,contributing nations,institutions,journals of significant citation,comprehensive references,and pivotal keywords.Additionally,our examination explored keyword cooccurrences,detailed timelines,and periods of heightened citation activity.This comprehensive search,from 2014 through 2023,was completed within a single day,on October 11,2023.RESULTS In total,2914 articles were ultimately included in the analysis.There was a rapid increase in annual publication output in 2015,followed by stable growth in subsequent years.Boninger,Michael L,is the most prolific author,whereas Ware JE has the most citations.The United States’global influence is significant,surpassing all other nations.The University of California System and Harvard University are the most influential academic institutions.J Bone Joint Surg Am is the most influential journal in this field.“Spinal cord injury”is the keyword that has garnered the most attention from researchers.The developmental pattern in this field is characterized by interdisciplinary fusion,with different disciplines converging to drive progress.CONCLUSION The academic development of the field of ET for pain in PMOP has matured and stabilized.Clinical management and rehabilitation strategies,along with the mechanisms underlying the relationship between ET and bone resorption analgesia,continue to be the current and future focal points of research in this field. 展开更多
关键词 Exercise therapy PAIN postmenopausal osteoporosis CITESPACE Bibliometric analysis Web of Science
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Serum sclerostin levels associated with lumbar spine bone mineral density and bone turnover markers in patients with postmenopausal osteoporosis 被引量:19
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作者 XU Xiao-juan SHEN Lin YANG Yan-ping LU Fu-rong ZHU Rui SHUAI Bo LI Cheng-gang WU Man-xiang 《Chinese Medical Journal》 SCIE CAS CSCD 2013年第13期2480-2484,共5页
Background Sclerostin, expressed exclusively by osteocytes, is a negative regulator of bone formation. To gain insights into the action of sclerostin in postmenopausal osteoporosis, we evaluated serum sclerostin level... Background Sclerostin, expressed exclusively by osteocytes, is a negative regulator of bone formation. To gain insights into the action of sclerostin in postmenopausal osteoporosis, we evaluated serum sclerostin levels in postmenopausal women and investigated its possible associations with bone turnover markers in patients with postmenopausal osteoporosis. Methods We detected serum sclerostin, and measured lumbar spine bone mineral density in 650 Chinese postmenopausal women. We also assessed serum levels of 13-isomerized C-terminal crosslinking of type I collagen, intact N-terminal propeptide of type I collagen, N-mid fragment of osteocalcin, 25-hydroxyvitamin D, and estradiol. Results Serum sclerostin levels were lower in postmenopausal osteoporotic women compared with non-osteoporotic postmenopausal women ((38.79+7.43) vs. (52.86+6.69) pmol/L, P 〈0.001). Serum sclerostin was positively correlated with lumbar spine bone mineral density (r=0.391, P 〈0.001) and weakly negatively correlated with [3-isomerized C-terminal crosslinking of type I collagen, intact N-terminal propeptide of type I collagen, N-mid fragment of osteocalcin (t= -0.225, P 〈0.001; r= -0.091, P=0.046; r= -0.108, P=0.018; respectively) in postmenopausal osteoporosis. There was no significant association of serum sclerostin with age, body mass index, 25-hydroxyvitamin D, and estradiol (r= -0.004, P=0.926; r=0.067, P=0.143; r=0.063, P=0.165; r= -0.045, P=0.324; respectively).Conclusion Sclerostin may be involved in the pathogenesis of postmenopausal osteoporosis and may play a role in bone turnover. 展开更多
关键词 sclerostin postmenopausal osteoporosis bone mineral density
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Postmenopausal Osteoporosis and Osteopenia Management with a Combination of Once-Monthly Oral Ibandronate and Cholecalciferol—A Systematic Review
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作者 Mauro Geller Mendel Suchmacher +4 位作者 Marcio Cohen Spyros G. E. Mezitis Flavia Wajnsztajn-Theil Karin G. Cunha Rafael Nigri 《International Journal of Clinical Medicine》 CAS 2023年第1期34-57,共24页
Postmenopausal osteoporosis and osteopenia are chronic and uncurable conditions that invariably lead to an increased risk of vertebral, hip, and femoral neck fracture if left untreated. Clinical guidelines establish, ... Postmenopausal osteoporosis and osteopenia are chronic and uncurable conditions that invariably lead to an increased risk of vertebral, hip, and femoral neck fracture if left untreated. Clinical guidelines establish, in general, pharmacological combinations allied to lifestyle changes as the mainstay of their management, and also increasing bone marrow density, lowering fracture risk, and improving quality of life are their main therapeutic goals. The objective of this systematic review was to analyze the available data in the scientific medical literature regarding the role of the ibandronate and cholecalciferol combination in postmenopausal osteoporosis and osteopenia management. Based on our results, we concluded that the above combination is safe and feasible for the clinical control of both conditions. 展开更多
关键词 IBANDRONATE CHOLECALCIFEROL postmenopausal osteoporosis postmenopausal Osteopenia Systematic Review
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Erxian decoction potentially prevents postmenopausal osteoporosis by modulating miR-335: a study based on bioinformatics analysis and preliminary clinical case validation
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作者 Hao-Qiang Huang Ye Feng +4 位作者 Xiao-Feng Shen Yu Zhou Li Qin Feng Xu Qing Wang 《Traditional Medicine Research》 2023年第6期1-8,共8页
Background:miRNAs are closely related to bone metabolism.Studies have shown that Erxian decoction can improve bone metabolism,possibly achieving this regulatory effect through miRNA targets.Netinfer was used to predic... Background:miRNAs are closely related to bone metabolism.Studies have shown that Erxian decoction can improve bone metabolism,possibly achieving this regulatory effect through miRNA targets.Netinfer was used to predict the miRNA targets of Erxian decoction for the treatment of postmenopausal osteoporosis,and the results were validated by clinical trials.Methods:In this study,we identified possible targets of Erxian decoction in osteoporosis by means of network pharmacological analysis and bioinformatic prediction.Fifteen cases of postmenopausal osteoporosis with kidney Yin and Yang deficiency(In traditional Chinese medicine,kidney Yin nourishes and moistens the tissues of the internal organs of the body,while kidney Yang promotes and warms the tissues of the internal organs of the body.)were treated with Erxian decoction for four weeks,and serum bone metabolism indices(P1NP,osteocalcin,andβ-CTX)and miRNA-335-5p expression were measured before and after treatment.Results:The constructed miRNA postmenopausal osteoporosis related gene network of the effective compound of the Erxian decoction has 296 points and 981 edges.The 39 postmenopausal osteoporosis related genes regulated by miRNA-335-5p were enriched in ossification,while the signaling pathways were enriched in rheumatoid arthritis,the Toll signaling pathway,the HIF-1 signaling pathway,and the MAPK signaling pathway.After taking Erxian decoction,the expression of the serum bone formation index(P1NP,osteocalcin)and miRNA-335-5p gene expression levels increased significantly.The alterations in P1NP and osteocalcin were correlated with the changes in miRNA-335-5p.Conclusion:Circulating miRNA-335-5p may serve as an important target of Erxian decoction in the treatment of postmenopausal women.The effect of Erxian decoction on bone formation is significant,but the underlying mechanism requires further investigation. 展开更多
关键词 Erxian decoction postmenopausal osteoporosis miRNA-335-5p bone formation BIOINFORMATICS clinical cases
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血清中Sclerostin、RANKL及OPG在老年股骨转子间骨折早期的含量改变及其临床意义 被引量:5
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作者 曹燕明 朱晓峰 胡健辉 《中国骨质疏松杂志》 CAS CSCD 北大核心 2013年第3期199-202,共4页
目的观察正常成年男女、老年男女及低外力作用下发生髋部骨折的老年男女血清中sclerostin、RANKL及OPG的含量变化并分析其临床意义。方法收集正常成年男女、老年男女及在2010年10月至2011年10月我院收治的低外力作用下发生股骨转子间骨... 目的观察正常成年男女、老年男女及低外力作用下发生髋部骨折的老年男女血清中sclerostin、RANKL及OPG的含量变化并分析其临床意义。方法收集正常成年男女、老年男女及在2010年10月至2011年10月我院收治的低外力作用下发生股骨转子间骨折的老年患者血清样本。采用酶联免疫吸附实验(ELISA)检测各血清样本中sclerostin、RANKL及OPG的水平。数据均以均数±标准差表示。采用SPSS13.0对数据进行统计分析。结果正常成年组(A组):sclerostin 76.6±10.5 pmol/l、RANKL 0.58±0.18 ng/ml、OPG 17.3±4.6 pmol/l;正常老年组(B组):sclerostin 102.0±12.3 pmol/l、RANKL 0.25±0.12 ng/ml、OPG 12.1±3.5 pmol/l;老年骨折组(C组):sclerostin 90.8±11.0 pmol/l、RANKL 0.23±0.13 ng/ml、OPG 11.7±3.5 pmol/l。结论由以上结果经统计分析后得出,sclerostin,RANKL及OPG在不同年龄层次其表达水平具有明显差异,与年龄有相关性。在老年骨折的早期阶段(骨折后3天内)血清中sclerostin的含量已出现显著变化。而RANKL及OPG的含量在骨折早期阶段并无明显改变。由此我们认为,骨折早期血清sclerostin的水平下降在促进骨折愈合的过程中可能起到一定作用,通过人为干涉抑制sclerostin的水平对预防老年髋部骨折可能存在一定的价值。 展开更多
关键词 sclerostin RANKL OPG 老年骨折 骨质疏松
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sclerostin在骨代谢中的作用和机制 被引量:7
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作者 张爽 高艳虹 《上海交通大学学报(医学版)》 CAS CSCD 北大核心 2015年第4期589-593,共5页
sclerostin是由SOST编码的糖蛋白,可以通过与Lrp4/5/6受体结合抑制Wnt信号通路,发挥调节骨代谢的作用。硬化性骨病、Van Buchem病、颅骨骨干发育异常等染色体异常性疾病及骨质疏松症均与SOST基因突变有关。近年来研究证实sclerostin不... sclerostin是由SOST编码的糖蛋白,可以通过与Lrp4/5/6受体结合抑制Wnt信号通路,发挥调节骨代谢的作用。硬化性骨病、Van Buchem病、颅骨骨干发育异常等染色体异常性疾病及骨质疏松症均与SOST基因突变有关。近年来研究证实sclerostin不仅可以通过多种途径阻碍成骨细胞分化而发挥抑制骨形成的作用,还可以通过促进破骨细胞生成和依赖RANKL的方式激活破骨细胞功能促进骨吸收。sclerostin单克隆抗体为骨质疏松症的治疗提供了新的途径,目前正在进行临床试验,其有效性及安全性需要进一步研究。 展开更多
关键词 sclerostin 骨代谢 WNT信号通路 骨质疏松
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抑制Dickkopf-1和Sclerostin表达对人成骨肉瘤细胞MG63骨代谢调节相关蛋白表达水平的影响 被引量:4
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作者 王吉利 万雷 +5 位作者 张志海 黄宏兴 黄红 肖本浩 魏合伟 曾国勇 《中医正骨》 2016年第9期13-18,共6页
目的:观察抑制Dickkopf-1和Sclerostin表达对人成骨肉瘤细胞MG63骨代谢调节相关蛋白表达水平的影响。方法:培养MG63细胞,构建沉默Dickkopf-1重组腺病毒载体和沉默Sclerostin重组腺病毒载体。将培养好的MG63细胞(每孔2×105个)分为4... 目的:观察抑制Dickkopf-1和Sclerostin表达对人成骨肉瘤细胞MG63骨代谢调节相关蛋白表达水平的影响。方法:培养MG63细胞,构建沉默Dickkopf-1重组腺病毒载体和沉默Sclerostin重组腺病毒载体。将培养好的MG63细胞(每孔2×105个)分为4组,Scr组以Scr腺病毒转染、Dickkopf-1组以沉默Dickkopf-1重组腺病毒载体转染、Sclerostin组以沉默Sclerostin重组腺病毒载体转染、Dickkopf-1+Sclerostin组以沉默Dickkopf-1重组腺病毒载体和沉默Sclerostin重组腺病毒载体共同转染。各组MG63细胞转染重组腺病毒48 h后以Western Blot法测定各组细胞中骨保护素(osteoprotegerin,OPG)、低密度脂蛋白受体相关蛋白-5(low density lipoprotein receptor-related protein-5,Lrp-5)、骨形态发生蛋白-2(bone morphogenetic protein-2,BMP-2)、成纤维细胞生长因子-2(fibroblast growth factor-2,FGF-2)、Runt相关转录因子-2(Runt-related transcription factor-2,Runx-2)、结缔组织生长因子(connective tissue growth factor,CTGF)、骨桥蛋白(osteopontin,OPN)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)等骨代谢调节相关蛋白的表达水平。结果:Dickkopf-1组的OPG表达量与Scr组、Sclerostin组比较,组间差异均无统计学意义(P=0.050,P=0.196);Sclerostin组、Dickkopf-1+Sclerostin组的OPG表达量均高于Scr组(P=0.010,P=0.000);Dickkopf-1组和Sclerostin组的OPG表达量均低于Dickkopf-1+Sclerostin组(P=0.000,P=0.000)。Dickkopf-1组、Sclerostin组、Dickkopf-1+Sclerostin组的Lrp-5表达量均高于Scr组(P=0.012,P=0.010,P=0.000);Dickkopf-1组的Lrp-5表达量与Sclerostin组比较,差异无统计学意义(P=0.119);Dickkopf-1组和Sclerostin组的Lrp-5表达量均低于Dickkopf-1+Sclerostin组(P=0.000,P=0.000)。Dickkopf-1组的BMP-2表达量与Scr组比较,差异无统计学意义(P=0.185);Dickkopf-1组的BMP-2表达量低于Sclerostin组(P=0.037);Dickkopf-1组和Sclerostin组的BMP-2表达量均低于Dickkopf-1+Sclerostin组(P=0.000,P=0.000)。Dickkopf-1组、Sclerostin组、Dickkopf-1+Sclerostin组的FGF-2表达量均高于Scr组(P=0.010,P=0.000,P=0.000);Dickkopf-1组的FGF-2表达量低于Sclerostin组和Dickkopf-1+Sclerostin组(P=0.000,P=0.000);Sclerostin组的FGF-2表达量低于Dickkopf-1+Sclerostin组(P=0.000)。Dickkopf-1组、Sclerostin组、Dickkopf-1+Sclerostin组的Runx-2表达量均高于Scr组(P=0.000,P=0.000,P=0.000);Dickkopf-1组的Runx-2表达量低于Sclerostin组和Dickkopf-1+Sclerostin组(P=0.000,P=0.000);Sclerostin组的Runx-2表达量低于Dickkopf-1+Sclerostin组(P=0.000)。Dickkopf-1组、Sclerostin组、Dickkopf-1+Sclerostin组的CTGF表达量均高于Scr组(P=0.010,P=0.000,P=0.010);Dickkopf-1组的CTGF表达量与Sclerostin组比较,差异无统计学意义(P=0.080);Dickkopf-1组和Sclerostin组的CTGF表达量均低于Dickkopf-1+Sclerostin组(P=0.000,P=0.004)。Dickkopf-1组、Sclerostin组、Dickkopf-1+Sclerostin组的OPN表达量均高于Scr组(P=0.002,P=0.000,P=0.000);Dickkopf-1组和Dickkopf-1+Sclerostin组的OPN表达量与Sclerostin组比较,差异均无统计学意义(P=0.050,P=0.170);Dickkopf-1组的OPN表达量低于Dickkopf-1+Sclerostin组(P=0.000)。Dickkopf-1组、Sclerostin组、Dickkopf-1+Sclerostin组的TNF-α表达量均低于Scr组(P=0.000,P=0.000,P=0.000);Dickkopf-1组的TNF-α表达量高于Sclerostin组和Dickkopf-1+Sclerostin组(P=0.000,P=0.000);Sclerostin组和Dickkopf-1+Sclerostin组的TNF-α表达量比较,差异无统计学意义(P=0.125)。结论:抑制MG63细胞Dickkopf-1和Sclerostin表达,均能上调具有骨形成和双向调节作用的骨代谢调节相关蛋白表达水平、下调具有骨吸收作用的骨代谢调节相关蛋白表达水平,其中抑制Sclerostin表达对骨代谢调节相关蛋白表达水平的影响强于抑制Dickkopf-1表达,而且抑制Dickkopf-1和Sclerostin表达在调节骨代谢调节相关蛋白表达水平方面具有协同作用。 展开更多
关键词 骨质疏松 基因沉默 DICKKOPF-1 sclerostin 腺病毒 MG63细胞
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Sclerostin单克隆抗体:即将出现的治疗骨质疏松症的新药物 被引量:3
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作者 朱晓峰 曹燕明 《中国骨质疏松杂志》 CAS CSCD 北大核心 2012年第6期568-572,541,共6页
骨质疏松是一种很常见的骨病,主要表现为单位体积内骨量减少、骨密度及骨强度的下降,加大骨折的风险增加。目前骨质疏松的药物治疗方法主要有:(1)激素替代治疗,(2)钙剂及维生素D,(3)抑制骨吸收,(4)促进骨形成,(5)中药治疗。Sclerostin... 骨质疏松是一种很常见的骨病,主要表现为单位体积内骨量减少、骨密度及骨强度的下降,加大骨折的风险增加。目前骨质疏松的药物治疗方法主要有:(1)激素替代治疗,(2)钙剂及维生素D,(3)抑制骨吸收,(4)促进骨形成,(5)中药治疗。Sclerostin是由骨细胞分泌的一种糖蛋白,拮抗性结合到LRP6和LRP6,阻断成骨细胞中Wnt信号/β-catenin信号,从而抑制成骨细胞分化、活动和生存。其作用机制使得Sclerostin成为治疗骨质疏松的一个新的靶点。目前,作用于Sclerostin的Sclerostin单克隆抗体已经进行了动物实验及临床前实验。实验结果显示Sclerostin单克隆抗体能促进骨形成,增加骨密度。目前Sclerostin单克隆抗体的安全性仍需进一步研究,但对治疗人类骨质疏松症有广阔的前景。 展开更多
关键词 sclerostin 骨质疏松症 单克隆抗体 骨代谢
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骨质疏松合并2型糖尿病老年男性患者血清Sclerostin水平及临床意义 被引量:6
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作者 叶燕彬 安荣泽 +3 位作者 齐新文 邝立鹏 陈军平 王兆杰 《中国医药导报》 CAS 2016年第21期99-102,共4页
目的分析骨质疏松合并2型糖尿病(T2DM)老年男性患者血清骨硬化蛋白(Sclerostin)表达水平及临床意义。方法选择2014年7月。2015年10月在遵义医学院第五附属(珠海)医院确诊骨质疏松症的老年男性患者80例,依据是否合并T2DM分为T2DM... 目的分析骨质疏松合并2型糖尿病(T2DM)老年男性患者血清骨硬化蛋白(Sclerostin)表达水平及临床意义。方法选择2014年7月。2015年10月在遵义医学院第五附属(珠海)医院确诊骨质疏松症的老年男性患者80例,依据是否合并T2DM分为T2DM组(合并T2DM)与NDM组(非糖尿病),每组各40例。比较两组患者的Sclerostin水平;比较两组患者血钙、血磷、空腹血糖(FPG)、糖化血红蛋白(HbA1c)等生化指标以及k~L4、股骨颈、Ward三角区及大转子区域骨密度数值。应用直线相关分析评估Sclerostin血清水平与骨密度相关性。结果T2DM组血清Sclerostin、FPG及HbA。。显著高于NDM组(均P〈0.01),而两组血钙、血磷比较差异无统计学意义(P〉0.05)。T2DM组股骨颈、Ward三角区及大转子区域骨密度较NDM低(P〈0.05或P〈0.01),而两组L2~L4的骨密度比较差异无统计学意义(P〉O.05)。相关性分析显示,血清Sclerostin与股骨颈及ward三角的骨密度呈负相关(r=-O.650、-0.674,均P〈0.05),而与大转子区域及L2~L4的骨密度无相关性(P〉0.05)。结论骨质疏松合并T2DM老年男性患者血清Sclerostin表达水平较高,且与骨质疏松部位、糖尿病病程及血糖水平有相关性。 展开更多
关键词 骨硬化蛋白 骨质疏松 2型糖尿病 骨密度
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抗Sclerostin单链抗体基因的构建、表达及活性分析 被引量:1
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作者 姚琦 张立才 +4 位作者 倪杰 侯宇 刘长振 郁卫东 张里程 《武警医学》 CAS 2013年第12期1047-1052,共6页
目的构建抗Sclerostin(SOST)单链抗体原核表达载体并对表达蛋白进行活性分析。方法提取抗SOST单克隆抗体5H3D1杂交瘤细胞总RNA,用RT-PCR方法扩增抗体轻链可变区基因(VL)和重链可变区基因(VH)并通过重叠延伸拼接(SOE)PCR方法,在VL和VH基... 目的构建抗Sclerostin(SOST)单链抗体原核表达载体并对表达蛋白进行活性分析。方法提取抗SOST单克隆抗体5H3D1杂交瘤细胞总RNA,用RT-PCR方法扩增抗体轻链可变区基因(VL)和重链可变区基因(VH)并通过重叠延伸拼接(SOE)PCR方法,在VL和VH基因之间引入Linker(Gly4Ser)3,连接成单链抗体SOST-scFv(VL-Linker-VH)。将scFv基因克隆至表达载体PET-22b(+)后转入HEK293细胞进行分泌表达,聚丙烯酰胺凝胶电泳SDS-PAGE鉴定表达产物,ELISA和West-blot检测表达蛋白的反应活性,茜素红结节染色法评估单链抗体对体外培养骨髓间充质干细胞成骨矿化的影响。结果 VL基因序列全长为339个碱基对,VH基因序列全长330个碱基对,均符合小鼠免疫球蛋白可变区基因特征,而SOST-scFv基因全长包括4个框架区(FR)、3个抗原互补决定区(CDR)以及具有抗体特征性的2个半胱氨酸残基;本研究构建的scFv全长687个碱基对,VL-Linker-VH为连接结构,SDS-PAGE分析表明大肠杆菌表达的scFv为可溶性蛋白,ELISA和West-blot检测证实表达scFv具有与SOST特异性结合的活性,细胞实验结果证实scFv能够促进骨髓间充质细胞成骨分化及矿化结节的形成。结论成功构建抗SOST单链抗体表达载体,而且表达的scFv产物具有确切的免疫结合活性以及体外诱导成骨分化、矿化作用,为该抗体应用于骨质疏松疾病治疗奠定了实验基础。 展开更多
关键词 骨硬化素 单链抗体 骨质疏松 表达 活性
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Effects of sclerostin antibody on bone healing 被引量:1
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作者 Atsushi Mihara Kiminori Yukata +5 位作者 Toshihiro Seki Ryuta Iwanaga Norihiro Nishida Kenzo Fujii Yuji Nagao Takashi Sakai 《World Journal of Orthopedics》 2021年第9期651-659,共9页
Promoting bone healing after a fracture has been a frequent subject of research.Recently,sclerostin antibody(Scl-Ab)has been introduced as a new anabolic agent for the treatment of osteoporosis.Scl-Ab activates the ca... Promoting bone healing after a fracture has been a frequent subject of research.Recently,sclerostin antibody(Scl-Ab)has been introduced as a new anabolic agent for the treatment of osteoporosis.Scl-Ab activates the canonical Wnt(cWnt)-β-catenin pathway,leading to an increase in bone formation and decrease in bone resorption.Because of its rich osteogenic effects,preclinically,Scl-Ab has shown positive effects on bone healing in rodent models;researchers have reported an increase in bone mass,mechanical strength,histological bone formation,total mineralized callus volume,bone mineral density,neovascularization,proliferating cell nuclear antigen score,and bone morphogenic protein expression at the fracture site after Scl-Ab administration.In addition,in a rat critical-size femoral-defect model,the Scl-Ab-treated group demonstrated a higher bone healing rate.On the other hand,two clinical reports have researched Scl-Ab in bone healing and failed to show positive effects in the femur and tibia.This review discusses why Scl-Ab appears to be effective in animal models of fracture healing and not in clinical cases. 展开更多
关键词 Canonical Wnt-β-catenin pathway Fracture healing osteoporosis Romosozumab sclerostin antibody
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Association of CA Repeat Polymorphism in Estrogen Receptor β Gene with Postmenopausal Osteoporosis in Chinese
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作者 耿力 姚珍薇 +3 位作者 杨洪昌 骆建云 韩力力 卢起 《Journal of Genetics and Genomics》 SCIE CAS CSCD 北大核心 2007年第10期868-876,共9页
Postmenopausal osteoporosis (PMO) is considered a polygenic disease. The estrogen receptor β (ESR2) gene is a candidate mediating the genetic influence on bone mass and the risk of osteoporosis. The aim of this s... Postmenopausal osteoporosis (PMO) is considered a polygenic disease. The estrogen receptor β (ESR2) gene is a candidate mediating the genetic influence on bone mass and the risk of osteoporosis. The aim of this study is to investigate the association of a cytosine-adenine (CA) repeat polymorphism in the fifth intron of the ESR2 gene with PMO in Chinese Han population. The CA repeat polymorphism was genotyped in a case-control study, involving 78 femoral neck PMO patients vs. 122 controls and 108 lumbar spine (L2-4) PMO patients vs. 92 controls. The (CA)n〈22 and (CA)n≥22 alleles were designated short (S) and long (L), respectively. ESR2 genotype was categorically defined as SS (2 S alleles), SL (having the mixed S and L alleles), and LL (2 L alleles). At both the femoral neck and the L2-4 region, LL genotype and L allele frequencies of the PMO group were significantly higher than those of the control group (P〈0.01). The subjects with the SL, the LL, and the combined SL and LL genotype had a significant increased risk of PMO when compared with those with the SS genotype (P〈0.05). After adjustments for age, years since menopause, menopausal age, and body mass index, logistic regression analysis showed that the subjects with the combined SL and LL genotype had increased risk of PMO when compared with those with the SS genotype both at the femoral neck (adjusted OR 4.923, 95% CI 1.986-12.203 , P=0.001) and the L2-4 (adjusted OR 2.267, 95% CI 1.121-4.598, P=0.023). This extensive association study has identified the ESR2 CA repeat polymorphism to be independently associated with PMO at the femoral neck and the L2-4 in Chinese Han population. The data also suggested that the presence of the L allele may dominantly increase the risk of PMO at the two regions. 展开更多
关键词 osteoporosis postmenopausal estrogen receptor β (ESR2) POLYMORPHISMS bone mineral density
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Study on the Correlation between Adiponectin and Bone Mineral Density in Postmenopausal Women from Guangxi Zhuang Autonomous Region
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作者 Ying Li Peizhao Shi +6 位作者 Songyi Mo Jiahui Li Xinling Ma Ziyang Fang Lingling Huang Ruiqun Lu Jinhua Wang 《Journal of Biosciences and Medicines》 2024年第5期178-189,共12页
Objectives: To explore the relationship between adiponectin (APN) and bone mineral density in this Zhuang ethnic group, thus providing a basis underpinning the prevention and treatment of osteoporosis (OP). Methods: Z... Objectives: To explore the relationship between adiponectin (APN) and bone mineral density in this Zhuang ethnic group, thus providing a basis underpinning the prevention and treatment of osteoporosis (OP). Methods: Zhuang women over 50 years old in Guangxi Zhuang Autonomous Region were included in the study. The broadband ultrasound attenuation (BUA) was adopted as the reference to calculate the T value. Quantitative ultrasonic bone density was measured on the right. Body composition measuring instrument was used to measure weight, fat, and muscle mass. Plasma APN level was detected by ELISA and blood lipids were detected by enzymatic method. Results: Plasma APN level was found with significant differences in the normal bone mineral density group, bone mineral density reduction group, and osteoporosis group (P β = −0.176, P = 0.001) when the partial correlation coefficient of APN is −0.210. Elevated APN was an independent risk factor for bone mineral density reduction (OR = 1.191, 95%CI: 1.004 - 1.407, P = 0.04) and OP (OR = 1.1337, 95%CI: 1.137 - 1.572, P Conclusion: Increased APN in postmenopausal women of Zhuang is an independent risk factor for OP. The application of APN in the OP screening and prevention of middle-aged and ageing Zhuang women still needs further research. 展开更多
关键词 postmenopausal osteoporosis ADIPONECTIN Broadband Ultrasound Attenuation
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糖皮质激素性骨质疏松大鼠Sclerostin表达变化的实验研究 被引量:1
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作者 任强 彭志 《菏泽医学专科学校学报》 2019年第2期6-9,44,共5页
目的探索建立糖皮质激素性骨质疏松症(GIOP)大鼠模型的方法;检测骨硬化蛋白(Sclerostin)在GIOP大鼠胫骨组织中的表达变化,初步探讨Sclerostin与GIOP的关系;初步探讨Sclerostin变化与调控GIOP的Wnt/β-catenin信号通路的关系。方法将30... 目的探索建立糖皮质激素性骨质疏松症(GIOP)大鼠模型的方法;检测骨硬化蛋白(Sclerostin)在GIOP大鼠胫骨组织中的表达变化,初步探讨Sclerostin与GIOP的关系;初步探讨Sclerostin变化与调控GIOP的Wnt/β-catenin信号通路的关系。方法将30只SD大鼠随机分为空白对照组、假手术组、实验组,每组10只。空白对照组正常喂养,不做任何处理;假手术组仅切开、缝合,不植入激素;实验组予以糖皮质激素(甲泼尼龙片)皮下植入,制备骨质疏松模型。测定大鼠的BMD测定;鼠骨组织取材、病理及HE染色;Real-timePCR检测大鼠骨组织中sclerostin基因的表达变化。结果GIOP大鼠模型成功建立;测定大鼠BMD含量,差异有统计学意义。病理切片及HE染色结果显示:GIOP组大鼠股骨组织的骨小梁破坏严重,骨小梁数量明显减少。Real-time PCR检测结果显示:实验组sclerostin的mRNA在骨组织表达成增高趋势,差异有统计学意义(P<0.05)。结论皮下植入激素(甲泼尼龙)可以成功建立GIOP大鼠模型;Sclerostin在糖皮质激素性骨质疏松症中表达升高;Sclerostin可通过影响Wnt信号通路的表达,对Wnt/β-catenin信号通路介导的成骨细胞增殖、分化以及成熟起到抑制作用,加速骨质疏松的发生。 展开更多
关键词 sclerostin 糖皮质激素 骨质疏松症 WNT信号通路 骨密度
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Sclerostin单克隆抗体治疗骨质疏松的研究进展 被引量:4
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作者 张阳洋 高艳虹 《中国骨质疏松杂志》 CAS CSCD 北大核心 2017年第10期1376-1380,共5页
硬骨素(Sclerostin)是由硬化性骨病(sclerosteosis,SOST)基因编码的蛋白质,可以通过与低密度脂蛋白受体相关蛋白5/6(low density lipoprotein receptor-related protein,LRP5/6)结合达到拮抗Wnt蛋白并抑制成骨的作用,已经作为新的药物... 硬骨素(Sclerostin)是由硬化性骨病(sclerosteosis,SOST)基因编码的蛋白质,可以通过与低密度脂蛋白受体相关蛋白5/6(low density lipoprotein receptor-related protein,LRP5/6)结合达到拮抗Wnt蛋白并抑制成骨的作用,已经作为新的药物靶点用于抗骨质疏松药物研发。目前,围绕Sclerostin单克隆抗体已经进行了许多基础研究和临床研究,结果提示该类药物可以提高骨量、促进骨形成、抑制骨吸收,对于骨质疏松有一定治疗效果。但该类药物应用后的副反应,对骨折的影响等方面的研究数据尚不足,有待完善进一步研究。 展开更多
关键词 骨质疏松 骨硬化蛋白单克隆抗体 Romosozumab Blosozumab
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A Clinical Study of Yigu Capsule (益骨胶囊) in Treating Postmenopausal Osteoporosis 被引量:7
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作者 张荣华 陈可冀 +2 位作者 陆大祥 朱晓峰 马晓昌 《Chinese Journal of Integrated Traditional and Western Medicine》 SCIE CAS 2005年第2期97-103,共7页
Objective: To observe the efficacy and safety of Yigu capsule (益骨胶囊, YGC), a Chinese herbal compound preparation, in treating postmenopausal osteoporosis (PMO) and to explore its possible mechanism. Methods: The c... Objective: To observe the efficacy and safety of Yigu capsule (益骨胶囊, YGC), a Chinese herbal compound preparation, in treating postmenopausal osteoporosis (PMO) and to explore its possible mechanism. Methods: The clinical study was conducted in a prospective, randomized, double blinded method lasting for 6 months with placebo and positive control. Two hundred and ten PMO patients with confirmed diagnosis were assigned into the YGC group, the calciferol group and the placebo group. Besides being administered element calcium, they were treated with YGC, calciferol capsule and placebo capsule respectively. And such symptoms as newly found fracture and ostealgia, bone mineral density (BMD) of the 2nd-4th lumbar vertebrae (L_ 2-4 ) and upper femur, blood and urinary indexes for bone metabolism, sex hormone level and adverse reaction that occurred in patients were observed.Results: In the YGC group, the total effective rate was 95.50%, with no new occurrence of fractures, which was significantly better than that in the other two groups (P<0.05). Moreover, in the YGC group,the increase rate of BMD was 9.83% in L_ 2-4 , 4.09% in femoral neck, 4.60% in Wards triangle, 3.00% in greater trochanter, which was also better than that in the placebo group (P<0.05, P<0.01). As compared with the placebo group, levels in the YGC group of urinary oxyproline hydroxyproline/creatinine, urinary calcium/creatinine were significantly lower, serum and bone alkaline phosphatase, osteocalcin, estradiol and estradiol/testosterone were significantly higher, but no difference was shown in the comparison of testosterone level. In the observation period, no abnormality in blood or urine routine, liver or renal function was found. Only mild, transient gastro-intestinal response occurred in individual patients, but it did not affect the treatment. Conclusion: YGC could treat PMO effectively, as it could obviously increase the BMD of lumbar vertebrae and coxafemoral bone, elevate the alleviating rate of ostealgia and incessant motion time, yet causing no newly found compressive fracture of vertebrae, or and any related adverse reaction. YGC could not only promote the formation, but also inhibit the absorption of bone as well as increase the sex hormone level. Therefore, it is a pure Chinese herbal compound preparation worthy of further research and development. 展开更多
关键词 postmenopausal osteoporosis TREATMENT Yigu capsule
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Efficacy and Safety of Risedronate Sodium in Treatment of Postmenopausal Osteoporosis 被引量:3
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作者 李裕明 张众志 +1 位作者 邓秀玲 陈璐璐 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2005年第5期527-529,共3页
Summary: To evaluate the efficacy and safety of risedronate sodium in treatment of postmenopausal osteoporosis, one-year randomized, double blind clinical trial was performed among 54 women with postmenopausal osteop... Summary: To evaluate the efficacy and safety of risedronate sodium in treatment of postmenopausal osteoporosis, one-year randomized, double blind clinical trial was performed among 54 women with postmenopausal osteoporosis. The changes were compared in bone mineral density (BMD), bone metabolism markers and adverse events after 12 months oral administration of risedronate sodium. BMD was measured by dual energy X-ray absorptionmetry (DEXA) and bone turnover marker was detected. The results showed that there was a significant increase in BMD of the lumbar spine (3.29 %±41.18 %, 4.51%±1.64 % respectively) after 6 and 12 months in the risedronate treatment group versus placebo control group (-0.62 %±0.24 %, 0.48 %±0. 18 % respectively). Bone turnover was decreased to a stable nadir over 6 and 12 months for resorption markers [N-Telopeptide (NTx), P〈0.05] and over 12 months for formation marker (ALP, P〈0.05; BGP, P〈0. 05). The safety profile of risedronate sodium was similar to that of placebo. There were no trends toward increased frequency of any adverse experience except for gastrointestinal symptoms (7.1%), rash (7.1%) and hematuria (3.6 %), which were usually mild, transient, and resolved with continued treatment. It was concluded that risedronate was an efficacious and safe drug in treatment of postmenopausal osteoporosis. 展开更多
关键词 risedronate sodium postmenopausal osteoporosis bone mineral density
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Association of Serum Dkk-1 Levels with β-catenin in Patients with Postmenopausal Osteoporosis 被引量:9
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作者 田峻 徐晓娟 +7 位作者 沈霖 杨艳萍 朱锐 帅波 朱习文 李成刚 马陈 吕林 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2015年第2期212-218,共7页
Wnt signaling plays an important role in the bone development and remodeling. The Wnt antagonist Dkk-1 is a potent inhibitor of bone formation. The aims of this study were firstly to compare the serum Dkk-1 levels in ... Wnt signaling plays an important role in the bone development and remodeling. The Wnt antagonist Dkk-1 is a potent inhibitor of bone formation. The aims of this study were firstly to compare the serum Dkk-1 levels in postmenopausal osteoporosis patients with age-matched healthy controls, and secondly, to assess the possible relationship between Dkk-1 and β-catenin, sclerostin, or bone turnover markers [CTX, PINP, N-MID-OT and 25(OH)D] in the setting of postmenopausal osteoporosis. A total of 350 patients with postmenopausal osteoporosis and 150 age-matched healthy controls were enrolled, and the serum levels of Dkk-1, β-catenin, sclerostin, OPG, and RANKL were detected by ELISA, and bone turnover markers [CTX, PINP, N-MID-OT and 25(OH)D] were measured by Roche electrochemiluminescence system in two groups. Serum Dkk-1 levels were significantly higher in postmenopausal osteoporosis group than in control group(P〈0.001). Univariate analyses revealed that serum Dkk-1 levels were weakly negatively correlated to β-catenin(r=–0.161, P=0.003) and OPG(r=–0.106, P=0.047), while multiple regression analysis showed a negative correlation between serum Dkk-1 levels with β-catenin(β=–0.165, P=0.009) and BMD(β=–0.139, P=0.027), and a positive correlation between serum Dkk-1 levels and CTX(β=0.122, P=0.040) in postmenopausal osteoporosis group. No similar correlations ware observed in control group. The results provided evidence for the role of Dkk-1 in bone metabolism and demonstrated the link of Dkk-1 and Wnt/β-catenin in some ways. 展开更多
关键词 osteoporosis postmenopausal catenin RANKL Serum remodeling negatively metabolism turnover matched
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