去势雌性山羊骨质疏松模型的特点

背景：加强骨质疏松模型的研究,对骨质疏松性骨折的防治非常必要。 目的：综述现有的山羊骨质疏松模型的特点,为骨质疏松和骨质疏松性骨折的防治提供帮助。 方法：应用计算机检索中国知网和PubMed数据库中2005-06/2011-02关于去势雌性山羊骨质疏松模型的文章,在标题和摘要中以“骨质疏松症、动物模型、山羊、卵巢切除”或“osteoporosis, animal model, goats, ovariectomy”为检索词进行检索。选择文章内容与建立骨质疏松模型的方法、评价标准,骨质变化等有关的研究,排除重复研究及建立雄性动物骨质疏松模型的研究。 结果与结论：初检得到48 篇文献,根据纳入标准选择21篇文章进行综述。山羊来源方便,容易处置,具有自动排卵和与成年妇女相似的排卵周期,是理想的实验动物材料;能获取大量血、尿和骨骼标本,是理想的制备骨质疏松模型的实验动物。去势法是建立骨质疏松模型常用的方法,山羊骨质疏松模型的建立将为骨质疏松和骨质疏松性骨折防治药物的开发、改进内置物设计等提供研究的基础。 关键词：卵巢切除术;骨质疏松;模型;雌激素;骨代谢;山羊 doi:10.3969/j.issn.1673-8225.2012.07.038             

补肾活血方药对去睾大鼠血清性腺激素及IL-6水平的影响

老年男性骨质疏松症已日益引起社会的关注 ,其发病率也逐年增高 ,而雄激素减少是老年男性骨质疏松的重要发病原因之一[1 ] 。既往的研究表明 ,补肾活血方药—骨康防治老年性骨质疏松症疗效显著 ,为进一步探讨中药骨康防治老年性骨质疏松症的作用机制 ,本实验观察补肾活血方药—骨康对去睾大鼠血清睾酮 (Ｔ)、雌二醇 (Ｅ2 )、黄体生成素 (ＬＨ)、卵胞生成素 (ＦＳＨ)、白细胞介素 - 6(ＩＬ - 6)水平变化的影响。材料和方法一、动物 :选用 8月龄雄性ＳＤ大鼠 ,体重 2 80～ 30 0ｇ,由广东省卫生厅实验动物中心提供。二、药物及试剂 :补肾活血中…     

计算机辅助骨形态计量学分析系统的构建与应用

本研究旨在构建计算机辅助的骨形态计量学分析系统。基本方法为利用显微镜、数码相机、计算机及相关软件构建不脱钙切片的显微图像数码整合系统,利用Freeplus和自编软件对每一幅图像进行基本测量,再根据骨形态计量学的定义,计算出反映骨量、骨结构与骨代谢变化的计量参数。此方法已应用于骨质疏松症的动物实验和临床研究,在骨质疏松性骨折风险预测和药物疗效评定中都发挥了重要作用。     

中药复方对成骨细胞增殖及骨密度的影响

背景：复方中药是由多种矿物植物动物等物质组成的复方药物,在治疗骨代谢疾病方面,能通过多途径,多靶点发挥综合治疗作用。 目的：研究复方中药对成骨细胞增殖及骨密度的影响,探讨复方中药对骨质疏松症的药理作用。 方法：回顾性分析以往经实验研究证实的某些复方中药对骨质疏松症动物模型成骨细胞增殖分化及骨密度的影响,分析影响复方中药促进骨形成的因素,通过对成骨细胞体外培养方法进行筛选,找出促进细胞增殖分化、提高骨密度的药物适宜剂量,与化学药物结果进行对照研究。 结果与结论：复方中药能够促进成骨细胞增殖分化、提高骨密度,在治疗骨质疏松症方面具有标本兼治、毒副作用小等优点,但复方中药在改善骨密度水平方面不及化学药物,并且应通过长期、大样本的临床研究,降低骨质疏松性骨折风险的干预作用。     

骨质疏松动物模型的研究现状

背景：骨质疏松的发病机制十分复杂,但又不能直接在人体上进行实验,需要复制类似人类骨质疏松的动物模型进行研究。 目的：全面分析各种骨质疏松动物模型的造模方法及优缺点,为今后研究骨质疏松症,在模型选择上提供参考。 方法：电子检索中国知识资源总库(CNKI)系列数据库和ESBCO Medline数据库1990-01/2010-07收录的骨质疏松模型的相关综述和论文报告。中文检索词为“骨质疏松,动物模型”;英文检索词为“osteoporosis,animal models”。共检索到469篇相关文献,对文章进行初审,纳入文献主题内容与此文联系紧密;原创、论点论据可靠的试验文章;观点明确,分析全面的文章。排除内容陈旧或重复文献及试验设计中不是采用随机对照试验的文章。 结果与结论：共纳入符合标准的38篇文献。目前用于骨质疏松症研究的动物模型主要有诱发性动物模型和转基因动物模型。各种骨质疏松动物模型可能只侧重于表现该疾病的某种病因、某一阶段、某些主要症状及某些病理生理变化,必须根据研究目的,选择合适的造模方法和实验动物。     

骨质疏松症的治疗进展

骨质疏松症是一种骨代谢性疾病,其发生发展主要是由骨形成和骨吸收失衡造成的.一旦发生骨质疏松,可严重影响患者的身心健康及生活质量,因此,如何防治骨质疏松症是极为重要的问题.目前,骨质疏松症的治疗方法主要有非药物治疗和药物治疗两大类.本文对近几年新型的骨质疏松症的治疗进展进行综述.     

可吸收生物玻璃注射体在骨质疏松大鼠椎体内的支撑及诱导成骨机制

文章快速阅读：  文题释义：可吸收生物玻璃注射体：为生物玻璃与磷酸钙骨水泥的复合物,主要成分为SiO₂、CaO、P₂O₃和Na₂O,与人体骨类似,能够在材料界面与人体骨组织之间形成牢固化学键,增加连接强度,提高移植物与界面的稳定性,传导性优于磷酸钙骨水泥。骨质疏松症模型：目前临床中主要有7种动物模型：①绝经后骨质疏松症模型,通过手术或药物“去势法”,模拟人类绝经后雌激素缺乏而导致的骨质疏松,最符合人体骨质疏松的发病特点,为目前研究骨质疏松症模型应用最多的模型方法;②老年性骨质疏松症模型,是目前惟一一种能证明增龄性骨脆性骨折的理想模型;③老年男性骨质疏松症模型可通过将雄性大鼠去睾18周;④内分泌代谢性骨质疏松症模型,可将雌性Wistar大鼠制成糖尿病模型后进行去势手术;⑤营养缺乏性骨质疏松症模型,通过高蛋白低钙饮食可模拟膳食不平衡导致的骨质疏松;⑥药物性骨质疏松症模型,通过糖皮质激素、维甲酸导致骨质疏松;⑦失用性骨质疏松症模型,通过全身或局部制动方法来模拟临床中继发骨折或其他手术后不同程度的制动,而导致的骨质疏松。 背景：生物玻璃与磷酸钙骨水泥复合形成的可吸收生物玻璃注射体,能在材料界面与人体骨组织之间形成牢固化学键,提高移植物与界面的稳定性。 目的：观察可吸收生物玻璃注射体在骨质疏松大鼠模型椎体内的支撑及诱导成骨机制。 方法：切除30只雌性SD大鼠双侧卵巢,制备骨质疏松模型。造模成功后,随机分成3组,在L3-5椎体骨缺损处分别置入聚甲基丙烯酸甲酯、注射性磷酸钙骨水泥和可吸收生物玻璃注射体。置入后12周取置入节段椎体,进行生物力学、降解性能、Ca、P、碱性磷酸酶、骨密度、骨形态发生蛋白2和转化生长因子β水平检测,以及骨组织切片观察。  结果与结论：可吸收生物玻璃注射体组的降解性能、抗压强度、表面羟基磷灰石沉积量、骨密度显著高于其余两组(P < 0.05),骨小梁相对体积、厚度和数量显著大于其他两组(P < 0.05),血清Ca、碱性磷酸酶、骨形态发生蛋白2和转化生长因子β水平显著高于其他两组(P < 0.05),血清P水平低于其他两组(P < 0.05)。结果表明,可吸收生物玻璃注射体可增强骨质疏松椎体内支撑力,诱导成骨,可能与提高骨形态发生蛋白和转化生长因子β的表达有关。 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程 ORCID: 0000-0003-3640-1589(郑红梅)     

药物治疗骨质疏松肱骨拉伸力学特性的对比

背景：力学性能指标是评价药物治疗骨质疏松动物模型效果的重要方法,以拉伸力学性能指标评价多种药物治疗老龄雌性骨质疏松模型大鼠的效果评价罕见报道。 目的：评定中药骨疏康胶囊、西药阿仑膦酸钠、维生素K、钙剂逸得乐对骨质疏松模型大鼠肱骨拉伸力学的影响。 方法：四五个月龄雌性Wistar大鼠180只分为6组,每组30只。除正常对照组外对所有大鼠于0周摘除双侧卵巢制备骨质疏松动物模型。骨疏康胶囊组动物每日给服骨疏康胶囊0.9 g/kg、阿仑膦酸钠治疗组动物每日给服阿仑膦酸钠1 mg/kg、维生素K组动物每日给服维生素K 0.1 mg/kg、钙剂组动物每日给服钙剂逸得乐2 mg/kg。15周后取大鼠左、右侧肱骨在电子万能试验机上以5 mm/min的实验速度进行拉伸实验,试样破坏后观察试样的断口形貌。 结果与结论：骨质疏松动物模型组大鼠肱骨拉伸实验最大载荷、最大应变显著小于正常对照组和骨疏康胶囊组、阿仑膦酸钠组、维生素K组(P < 0.05);钙剂组最大载荷,最大应力,最大应变和模型组差异不显著(P > 0.05)。结果说明,中药、西药、维生素K治疗骨质疏松模型大鼠拉伸力学性能均有一定提高,中药骨疏康胶囊治疗骨质疏松模型大鼠拉伸力学性能明显提高。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

骨质疏松性骨折的特点及临床与研究进展

骨质疏松性骨折是骨质疏松症最严重的后果,骨质疏松性骨折的患病率与年龄、性别、种族等因素密切相关。骨质疏松性骨折的特点是:骨质量差,骨折愈合时间迟缓,再骨折的发生率较高。骨质疏松性骨折治疗包括骨折的外科治疗和抗骨质疏松症的治疗。抗骨质疏松的治疗,一方面可以提高骨量、改善骨质量,另一方面有降低再骨折风险的重要临床意义;骨折的外科治疗应以简便、安全、有效为原则。由于骨的质量差,骨折后内固定物及植入物固定的牢固程度差,易发生松动,因此需要寻找更接近骨刚度和骨弹性模量的内植物,研发能更快速、有效改善骨量与骨质量的制剂以改进骨质疏松性骨折的治疗。在骨质疏松性骨折的治疗过程中骨折的外科治疗和抗骨质疏松症的治疗应并重,才可以达到更理想的骨质疏松性骨折的治疗效果。     

促骨形成药物的研究进展

骨质疏松症所引起的脆性骨折严重影响老年人的健康和生活质量。目前,抗骨质疏松治疗的药物主要有骨吸收抑制剂和骨形成促进剂两大类;而临床用于治疗的大多为骨吸收抑制药物,仅有重组人甲状旁腺激素是唯一上市的治疗骨折疏松的促骨形成药物。胰岛素样生长因子-1、钙离子受体拮抗剂、骨形成蛋白、Wnt信号通路阻滞剂等一批新型促骨形成药物正在体内和体外实验之中。随着研究的不断深入,这些促骨形成药物必将会有广阔的应用前景。     

构建骨质疏松动物模型研究进展

骨质疏松症(osteoporosis,OP)是一组代谢性骨病,其原因复杂,主要特点为骨微结构破坏、骨量低下、骨脆性增加。随着社会生产力的稳步提升,老龄化社会成为多数发达国家及部分发展中国家的社会形态。正因为老年人在人口结构的占比不断攀升,骨质疏松症的占比也不断增高,所以如何防治骨质疏松症已成为当前人们关注的重点和难点。为了研制更为有效的临床药物及推广正确的诊疗康复方案,构建行之有效的骨质疏松实验动物模型起着关键的作用,这也将推进临床转换这一过程。本文就如何构建骨质疏松动物模型进行系统的讲述,对涵盖动物模型的造模方法进行了详细的综述。     

近5年骨质疏松英文文献的计量学及可视化分析：Web of Science来源数据

文题释义：CiteSpace：是由美国德雷塞尔大学学者陈超美博士利用JAVA语言开发，应用于科学文献可视化分析的软件，通过对某一研究领域大量文献数据进行共现和共被引分析，可对该领域的研究前沿和发展趋势作出分析和预测，目前国内医学领域已有应用。 突现词：是一段时间内出现频次或使用频率较多的词，它能探测某一学科领域发展趋势和突变点，在一定程度上可揭示具有潜在价值的研究方向。 背景：骨质疏松一直是医学研究的热点，对骨质疏松研究领域的英文文献进行可视化分析，能更直观地了解该领域的研究现状、热点及前沿，有助于科研人员把握科研选题及方向。 目的：对有关骨质疏松的英文文献进行计量、共现、共被引及可视化分析，探索该领域近5年的研究现状、热点及前沿。 方法：以Web of Science(WOS)中Science Citation Index Expanded(SCI-E)收录的2015至2019年骨质疏松相关文献为对象，应用CiteSpace软件进行作者、机构、国家、关键词共现分析，被引作者、文献、期刊共被引分析，并绘制可视化图谱。 结果与结论：①共得到2 980篇文献，高产国家包括中国、美国、日本、韩国、英国等，主要研究机构有匹兹堡大学、哈佛大学、麦克马斯特大学、牛津大学等世界知名大学，上海交通大学占有一席之地。②高产作者HONG-WEN DENG关注基因与骨质疏松机制；HIROYUKI KATO、YUKIO NAKAMURA、TAKAKO SUZUKI共同关注地诺单抗、伊班膦酸等抗骨质疏松药物开发；JONATHAN D ADACHI关注维生素D与骨质疏松、骨代谢的研究；WILLIAM D LESLIE关注双能骨密度仪评估骨质疏松；JA KANIS关注抗骨质疏松的适宜人群及时机。《国际骨质疏松症杂志》《骨与矿物研究杂志》收录文献最多；《新英格兰医学杂志》《柳叶刀》《美国医学会杂志》等顶级刊物同样关注骨质疏松研究成果。③研究学科涉及临床及基础学科，以基础学科为主。抗骨质疏松药物开发获得进展是目前基础医学研究重要切入点。缺乏引起的骨质疏松、唑来膦酸、糖皮质激素诱发的骨质疏松、脂肪量、卵巢切除术、骨质疏松、矿物质密度、卵巢癌组、抗骨质疏松药、骨代谢是骨质疏松研究前沿领域。④2015至2016年，动物研究、老年骨质疏松是热点；2016至2017年，随机试验的设计、成人骨代谢、体力活动的干预是此阶段新兴领域；2017至2019年，糖皮质激素诱导的骨质疏松、间充质干细胞，细胞通路激活等关键词取得了爆发增长，是目前骨质疏松研究新兴领域。⑤结果表明，应用CiteSpace进行骨质疏松英文文献计量能相对直观地展示近5年整体发展，在选题参考内容和发展方向能够骨质疏松学者提供参考，结果具有一定意义。 ORCID: 0000-0001-6523-1035(张强) 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程     

Smokeless tobacco and osteoporosis: a new relationship?

Osteoporosis is a common disorder of bone predominantly affecting postmenopausal women in which bone mineral density declines making bone more likely to break. Although cigarette smoking is a well-established risk factor for osteoporosis, smokeless tobacco (ST) use has never been suggested or evaluated as a risk factor for this bone disorder. This would be important to consider since in certain regions of the world, ST use is more prevalent than cigarette smoking, particularly among women. This paper reviews the animal and human evidence lending support to this new hypothesis, as well as the epidemiology of ST use that underscores the potential impact this modifiable behavior might have on osteoporosis world wide.     

Bone regeneration related to calcium phosphate-coated implants in osteoporotic animal models: a meta-analysis

Background: Osteoporosis is a frequent human metabolic bone disorder. Prospectively, global ageing of populations will lead to a major increase of subjects being diagnosed with osteoporosis and in need for dental rehabilitation. However, as local osteoporosis of the jaws affects bone quantity and quality of edentulous regions, osseointegration of dental implants might be hampered. Consequently, calcium phosphate ceramic-coated implants have been suggested to compensate for low bone quantity/density and for impaired bone healing in osteoporosis. Nonetheless, up to now no meta-analytical assessment of the relevant preclinical literature to quantify such a possible positive effect has been undertaken. Materials and Methods: PubMed search, limited to animal models, to identify a possible positive effect of calcium phosphate-coated implants on bone regeneration, was carried out. Further, the reference lists of related review articles and publications selected for inclusion in this review were systematically screened. The primary outcome variables were bone-to-implant contact percentage as assessed histomorphometrically and mechanical stability testing. Results: The electronic search in the database of the National Library of Medicine resulted in the identification of 2704 titles. These titles were initially screened by the two independent reviewers for possible inclusion, resulting in further consideration of 51 publications. Screening the abstracts led to 22 full-text articles. From these articles, 16 reports were excluded. Finally, six of these original research reports could be selected for evaluation. Additionally, eight publications were identified by manual search. Thus, a total of 14 articles were included for analysis. Conclusions: It was concluded that (1) in osteoporotic animal models calcium phosphate ceramic-coated implants are associated with improved bone-to-implant healing as compared to noncoated implants. Moreover, (2) essentially due to quality characteristics of the analyzed original research articles a negative impact of osteoporosis on bone-to-implant healing could not be confirmed. Besides, (3) the established positive bone-to-implant healing effect of calcium phosphate ceramic coatings does not differ between osteoporotic and nonosteoporotic, healthy animal models.     

构建骨质疏松动物模型建模方法的改进及评价

BACKGROUND: Animal models of osteoporosis play an important role in the research of the pathogenesis, occurrence and development of osteoporosis, as well as in the clinical diagnosis, prevention and treatment of osteoporosis.   OBJECTIVE: To summarize and discuss the establishment and research ideas of osteoporosis models, explore the current situation and advance of osteoporosis models, compare the advantages and disadvantages of various methods, and provide evidence for clinical investigation. METHODS: A computer-based online search was conducted in SinoMed, VIP, Wanfang and PubMed databases by using the key words of “animal model, osteoporosis” from January 1969 to October 2015. The language was limited to both Chinese and English. Relevant articles were screened according to inclusion and exclusion criteria. The documents about the methods of osteoporosis model preparation, method improvement as well as their advantage and disadvantage were summarized. RESULTS AND CONCLUSION: A total of 576 articles were included. Among them, articles published earlier, duplicated, and similarly were excluded, and 53 articles were finally included. Various animal models of osteoporosis may only focus on the certain causes, certain stage, some of the main symptoms and some pathophysiological changes of disease. Accordingly, appropriate modeling methods and experimental animals should be selected based on research objective. Rat undergoing castration is the most commonly used model in the modeling of osteoporosis. Among drug methods for constructing osteoporosis model, glucocorticoids is the most commonly used one. Disuse method and nutritional method have limitations, and always combined with castration and drug methods. The effects of gene transfer, gene mutation and brain-derived model deserve further investigation.       

Viewpoint: Dried plum, an emerging functional food that may effectively improve bone health

Osteoporosis is a debilitating disorder that affects both female and male, albeit to a greater extent in women than men. As the demographic shift to a more aged population continues, a growing number of men and women will be afflicted with osteoporosis and a search for potential non-pharmacological alternative therapies for osteoporosis is of prime interest. Aside from existing drug therapies, certain lifestyle and nutritional factors are known to reduce the risk of osteoporosis. Among nutritional factors, recent observations suggest that dried plum, or prunes (Prunus domestica L.) is the most effective fruit in both preventing and reversing bone loss. Animal studies and a 3-month clinical trial conducted in our laboratories have shown that dried plum has positive effects on bone indices. The animal data indicate that dried plum not only protects against but more importantly reverses bone loss in two separate models of osteopenia. Our initial animal study indicated that dried plum prevented the ovariectomy-induced reduction in bone mineral density (BMD) of the femur and lumbar vertebra. In another study, to mimic established osteoporosis, rats were ovariectomized and allowed to lose bone before the initiation of treatment. Dried plum as low as 5% (w/w) restored BMD to the level of intact rats. More importantly, dried plum reversed the loss of trabecular architectural properties such as trabecular number and connectivity density, and trabecular separation. We have also shown the effectiveness of dried plum in reversal of bone loss due to skeletal unloading. Analysis of BMD and trabecular bone structure by microcomputed tomography (μCT) revealed that dried plum enhanced bone recovery during re-ambulation following skeletal unloading and had comparable effects to parathyroid hormone. In addition to the animal studies, our 3-month clinical trial indicated that the consumption of dried plum daily by postmenopausal women significantly increased serum markers of bone formation, total alkaline phosphatase, bone-specific alkaline phosphatase and insulin-like growth factor-I by 12, 6, and 17%, respectively. This review summarizes the findings of studies published to date which examine the beneficial effects of dried plum on bone in both female and male animal models of osteoporosis as well as the only published clinical study.     

骨髓间充质干细胞移植治疗骨质疏松的研究进展

骨质疏松症被定义为一种系统性骨骼疾病,其特征是骨量低、骨组织微结构恶化、骨脆性和骨折易感性增加。 目前有2亿多人患有骨质疏松症,但由于人口老龄化和人均寿命延长,受影响的人数仍在急剧增加,这是一个重大的公共卫生问题。目前,治疗骨质疏松症的药物开发已经取得了重大进展,但药物治疗并不能逆转骨丢失,且会给患者带来一系列毒副作用。大量研究表明,骨髓间充质干细胞的归巢作用、成骨分化和细胞因子作用在骨质疏松发病过程中发挥重要作用。 移植骨髓间充质干细胞作为一种新方法,不仅能避开药物治疗的副作用而且能从根本上治疗骨质疏松,具有巨大的潜能和应用价值,但许多问题也有待解决。     

骨小梁Micro-CT图像形态计量学参数计算方法综述

骨质疏松症是骨科领域的研究热点之一,研究发现,除骨密度(骨量)改变的因素外,骨小梁的结构变化也是患病的重要影响因素。骨小梁形态计量学分析是研究骨小梁结构形态变化的一种重要方法。基于骨小梁的Micro-CT图像介绍部分骨小梁形态学参数的计算方法,主要包括骨小梁各向异性、连通性、结构模型指数以及纹理等不同特征,同时列举部分相关研究实例,总结上述形态学参数的适用性以及优缺点,为更加有效地评价骨质疏松状态以及药物治疗效果提供依据。     

Preclinical development of agents for the treatment of osteoporosis.

Because of the high cost and long time frame of clinical testing, animal models play a crucial role in the identification and selection of agents for the treatment of osteoporosis. The use of animal models early in a program focuses on the establishment of efficacy, while animal models used later in a program to examine bone safety. More specifically, animal models are used to gain information on the skeletal mechanism of action, to examine multiple skeletal sites (axial and appendicular), and to examine the effects of higher doses than will be used in humans. Animal models also predict the usefulness of surrogate markers in clinical trials, such as formation and resorption markers, as well as bone density. The hazard of using surrogate markers for fracture prevention is highlighted by high dose fluoride administration, which can increase bone density (considered a strong predictor of fracture protection) while not protecting against fractures. Estrogen-deficient models are most commonly used to mimic the postmenopausal bone loss in women; these models are characterized by increased bone turnover and a negative bone balance. The timing of the administration of the new therapy in animal models can help determine whether the agent will be more effective in the prevention of osteoporosis or in the treatment of established osteoporosis. New methods for the measurement of bone mass or volume are less invasive, require shorter acquisition time, and have enhanced resolution, resulting in increased knowledge concerning architectural changes and specific sites of bone deposition. Finally, the measurement of biomechanical strength of bones from animal models can be used to predict protective effects on fracture rates in clinical trials. When used in combination with other methods, animal models can greatly increase our understanding of the pathophysiology of osteoporosis and can expedite the development of new therapies.