雌激素受体α、转化生长因子β1在去势大骨组织中的表达及意义

骨质疏松症是以低骨量及骨组织微结构退变为特征的一种全身性骨骼疾病,伴有骨脆性增加.绝经后骨质疏松症为多因素引起的代谢性骨病,雌激素缺乏是主要原因.我们通过建立绝经后骨质疏松模型,观察去势大鼠中不同时期胫骨雌激素受体(ER)α、转化生长因子(TGF)β1原位杂交情况,来探讨它们在去势后骨质疏松发病机制中的作用,对于临床防治骨质疏松提供参考.     

骨形态发生蛋白2（BMP-2）诱导血管钙化相关机制的新进展

研究表明血管钙化是一个类似成骨的主动、可预防和可逆转的高度可调控的生物学过程。骨形态发生蛋白（bone morphogenetic proteins,BMPs）家族作为转化生长因子β（transforming growth f a c t o r-β,TG F-β）超家族的成员,因具有诱导骨形成的特点而得名,到目前为止,已发现3 0余种BMP成员,其中BMP-2是一类唯一能够单独诱导骨组织形成的局部生长因子。目前有关动脉粥样硬化及血管钙化中BMP-2作用机制的研究日益增多。本文就近年BMP-2诱导动脉钙化（arterial calcification,AC）的相关研究进展作一综述。     

雌激素受体基因多态性与骨质疏松

从雌激素的结构和功能、雌激素受体与骨代谢、人工破坏雌激素受体基因小鼠模型的建立、雌激素受体基因突变的男性病例分析、雌激素受体的同工型及雌激素受体基因多态性等 6个部分综述雌激素及其受体基因在骨质疏松发病中的作用及意义 ,旨在阐明骨质疏松症 ,尤绝经后骨质疏松症的发病及分子机制 ,为基础和临床研究提供系统的思路。     

中药补肾活骨方对去势骨质疏松大鼠骨代谢的影响

背景：中药补肾活骨方可有效防治骨质疏松症,但其具体的药理学机制仍不是很清楚。25-羟基维生素D3和1,25-二羟基维生素D3是调节骨吸收与骨形成的重要的偶联因子。 目的：观察补肾中药对去势骨质疏松大鼠骨密度、骨生物力学、血清及肝肾组织中25-羟基维生素D3和1,25-二羟基维生素D3水平的影响。 方法：健康雌性SD大鼠108只随机等分为假手术组、模型组和治疗组。后2组摘除双侧卵巢,导致雌激素缺失,从而诱导骨质疏松症模型。治疗组大鼠造模后以中药补肾活骨方2 mL灌胃,2次/d。 结果与结论：与模型组相比,治疗组股骨头骨密度明显提高(P < 0.05),最大应力和最大负荷指数明显增强(P < 0.05),血液、肝脏和肾脏组织中25-羟基维生素D3和1,25 二羟基维生素D3水平明显提高(P < 0.05);且接近于假手术组(P < 0.05)。提示补肾中药在雌激素缺失早期即可在分子水平上调节25-羟基维生素D3和1,25-二羟基维生素D3的表达水平,激活骨代谢提高骨密度增强骨质量达到预防骨质疏松的作用。关键词：补肾活骨方;1,25-二羟基维生素D3;骨密度;骨生物力学;骨质疏松症;骨代谢 doi:10.3969/j.issn.1673-8225.2012.15.006 中图分类号: R318  文献标识码: A       

绝经后骨质疏松症患者细胞因子、骨密度及雌激素水平的关系

绝经后骨质疏松症是指绝经后妇女由于体内卵巢功能低下，雌激素水平低落，骨偶联过程失调，破骨细胞的骨吸收大于成骨细胞的骨形成作用所导致的骨量减少，骨脆性增加，进而易于发生骨折的代谢性骨疾病。雌激素水平降低是绝经后骨质疏松发病的首要原因，本文旨在观察绝经后骨质疏松症（PMOP）的雌激素水平与细胞因子的关系。     

骨形态发生蛋白与骨质疏松症

背景:骨形态发生蛋白能够诱导骨髓间质充质细胞分化为成骨细胞或成软骨细胞,并能够抑制破骨细胞活性,为治疗骨质疏松症开辟了一条新的途径。目的:综述骨形态发生蛋白与骨质疏松症的研究进展,以便寻求有效控制手段,指导临床合理用药和新药开发。方法:应用计算机检索CNKI和PubMed数据库中1995-01/2010-06关于骨形态发生蛋白及骨质疏松症的相关文章,检索词分别为"骨形态发生蛋白;细胞因子;骨;骨质疏松症"和"bone morphogenetic protein;cytokines;bone;osteoporosis",语言分别设定为中文和英文。选择内容与骨形态发生蛋白和骨质疏松症相关的文章,同一领域文献则选择近期发表或发表在权威杂志文章,排除重复研究或Meta分析类文章。结果与结论:收集到287篇相关文献,排除不符合标准的文献,共纳入30篇符合标准的文献。经分析得出以下结论:骨形态发生蛋白促进骨髓间质细胞向成骨细胞方向转化,有利于更合理选择临床用药,有效地预防骨质疏松的进展。骨形态发生蛋白能够明显促进成骨活性,但其作用机制尚未完全清楚,有可能是多因素共同的协同作用,通过该方面的机制研究可指导临床用药和新药开发。     

雌激素类治疗骨质疏松研究进展

雌激素在骨质疏松发生中的作用已获共识 ,雌激素可通过甲状旁腺素、降钙素和维生素D发挥间接作用 ,从而保持正常骨代谢过程。当内源性雌激素缺乏时 ,骨量丢失 (绝经后的妇女每年丢失骨量约 4.2 % ) ,女性一生中有 1 / 3的时间在绝经后度过 ,因此这一问题更为突出。并发骨质疏松的可能性也随之增加 ,在西方国家女性骨质疏松发病率明显高于东方妇女 ,雌激素替代(ERT)是本症的重要治疗措施。但是 ,用雌激素替代疗法有促发子宫内膜癌、乳腺癌和阴道出血的危险 ,历时 50余年的雌激素替代疗法被广泛接纳与应用 ,但由于不良反应较多而受到限制[1 …     

PMO患者血清E2、IL-6及IGF-Ⅰ水平的临床观察

目的：通过观察绝经后骨质疏松症（PMO）患者血清E2、IL-6及IGF-Ⅰ含量的变化,探讨E2、IL-6及IGF-Ⅰ在绝经后骨质疏松症发病机理中的作用。方法：根据腰椎骨密度（BMD）扫描结果,将受试者分为三组,即绝经后骨质疏松组32例、绝经后非骨质疏松组30例、绝经前健康组30例。采用放免法测定血清IL-6、BGP、IGF-Ⅰ水平,用化学发光免疫分析法测定血清E2水平,同时测定血清P、Ca、AKP水平。结果：绝经后妇女血清IL-6水平高于绝经前妇女,骨质疏松组又高于非骨质疏松组。IL-6与BMD、E2呈负相关关系（r分别为-0．587、-0．438,P〈0．05）,与BGP呈正相关关系（r=0．545,P〈0．05）。绝经后妇女IGF-Ⅰ含量降低,骨质疏松组IGF-Ⅰ含量最低。IGF-Ⅰ与BMD、E2呈显著正相关关系（相关系数r分别为0．569、0．433,P〈0．01）,与年龄呈显著负相关关系（r=-0．538,P〈0．01）。结论：绝经后骨质疏松为高转换率骨质疏松,IL-6高表达与骨质疏松症发病以及雌激素减少有关,雌激素水平下降可导致IL-6分泌的增多。体内雌激素还有助于维持IGF-Ⅰ的水平,绝经后骨质疏松患者体内IGF-Ⅰ水平明显下降。IL-6分泌增多、IGF-Ⅰ水平下降均可以导致骨吸收超过骨形成,引起骨丢失和骨质疏松症的发生。因此,IL-6、IGF-Ⅰ可作为一种预测骨质疏松症发病的检测手段。合理应用雌激素、IGF-Ⅰ可预防绝经后骨质疏松症的发生。     

骨代谢标志物与不同类型骨质疏松症的相关性研究

目的:比较不同类型骨质疏松症患者血清中骨代谢标志物的水平差异以及骨代谢标志物之间的相关性。方法:采用免疫电化学发光法检测2016年6月至2017年12月在我院确诊为骨质疏松无骨折患者134例,骨质疏松伴骨折患者118例,甲状旁腺功能亢进合并骨质疏松症患者126例和我院体检中心健康人群116例受试对象血清中I型前胶原氨基端延长肽(Procollagen type I N-terminal peptide,P1NP)、骨钙素(N-terminal midfragment of osteocalcin,N-MID)、I型胶原羧基端肽β特殊序列(βisomer of the C-terminal telopeptide of type I collagen,β-CrossLaps)、血清25羟维生素D(25-hydroxyvitamin D,25-OH(vit)D)、甲状旁腺素(Parathyroid hormone,PTH)的水平。结果:三种不同类型骨质疏松症患者血清中PINP及β-Crosslaps的水平均明显高于健康对照组(P0.05),其中PTH增高性骨质疏松组增加最为明显;各组受试对象中女性患者血清25-OH(vit)D水平均明显低于同组男性患者(P0.05),PINP、β-CrossLaps、N-MID的水平与同组男性患者相比均呈增加的趋势;Pearson相关性分析结果显示PTH与25-OH(vit)D呈负相关,PINP与N-MID,β-CrossLaps与N-MID,PINP与β-CrossLaps均呈正相关(P0.05)。结论:分析骨代谢标志在不同类型骨质疏松症患者血清中的水平差异及骨代谢标志物之间的相关性,可合理评价骨组织的转换率,有利于早期发现骨代谢紊乱,能更有效地预防骨质疏松症的发生与发展,减少骨质疏松合并骨折的发生率。     

骨质疏松的分子遗传学研究进展

骨质疏松是导致老年性骨折的常见疾病，遗传因素在骨质疏松的发病机理中占有重要地位。本文从分子遗传学角度简述了维生素D受体基因、雌激素受体基因、Ⅰ型胶原α链基因，甲状旁腺素,钙素受体基因，转化生长因子β基因等基因多态性与骨质疏松之间关系。     

Regulatory mechanisms in vascular calcification

Vascular calcification is increasingly recognized as a significant contributor to cardiovascular morbidity and mortality as well as a biologically regulated process potentially subject to prevention and reversal. Both coronary and aortic calcification are common and influence plaque rupture, angioplasty and surgical complications, and compensatory enlargement. Aortic calcification increases aortic rigidity and contributes to cadiac ischemia, left ventricular hypertrophy, heart failure, and stroke. Calcification is also common in aortic valve leaflets further compounding adverse hemodynamic effects. Vascular calcification has often been attributed to "passive" crystallization. However, functional similarities between atherosclerotic lesions and bone contradict this view and indicate that it is no more "passive" than in embryonic bone formation or bone repair. Similarities include presence of all the major components of bone osteoid, bone regulatory factors, and subpopulations of artery wall cells that retain osteoblastic lineage potential. Several animal models for vascular calcification are available. Spontaneous vascular calcification occurs in null mice for matrix GLA protein (MGP), a small matrix protein of unknown function, and osteoprotegerin (OPG), known to modulate osteoclast differentiation. Vascular calcification may also be induced by feeding vitamin D and calcium or warfarin to normal animals, or by fat-feeding mice null for apoE or the LDL-receptor. Overall, regulation of vascular calcification is a growing field with surprising mechanisms and connections to other fields of biology.     

Cardioprotective effects of ovarian hormones and the HERS in perspective

The increased population of women in menopause living in the industrialized countries is associated with an increase of diseases which are dependent or facilitated by a state of estrogen deficiency such as cardiovascular and cerebrovascular diseases. Several studies have shown that estrogen replacement therapy reduces the occurrence of coronary and may be of cerebrovascular disease by nearly 50% in treated women compared to non-users. These findings are supported by the evidence that estrogens have a beneficial effect on cholesterol metabolism and deposition, contributing to the inhibition of atherosclerotic plaque formation in arterial walls as well as a direct effect on the vessel wall. Progestins may, in some cases, counteract the beneficial effect of estrogens upon cardiovascular functions. More androgenic progestins may have a detrimental effect upon vascular reactivity while less androgenic progestins seem not to reduce the beneficial effect of estrogens. Of interest, continuous combined administration of hormone replacement therapy seem to be preferable for women with coronary artery disease or for those with increased cardiovascular risk. Case-control and cohort studies have shown that estrogen progestin therapy is associated with a significant reduction of cardiovascular mortality and morbidity. The HERS study has added critical data regarding the cardioprotective effect of hormone replacement therapy in elderly women with proven coronary artery disease. Because of the several methodological and statistical flaws of the HERS study, further studies are warranted to evaluate the effect of hormone replacement therapy on cardiovascular prognosis. Large scale randomized studies will evaluate the effect of estrogen and estrogen-progestin replacement therapy upon cardiovascular events in menopausal women. Until completion of these studies hormone replacement therapy in women with increased cardiovascular risk should be seen with no enthusiasm but also with no fear.     

Association between atherosclerosis and osteoporosis,the role of vitamin D

The latest data support the correlation of atherosclerosis and osteoporosis, indicating the parallel progression of two tissue destruction processes with increased fatal and non-fatal coronary events, as well as higher fracture risk. Vitamin D inadequacy associated with low bone mineral density increases fall and fracture risk, leads to secondary hyperparathyroidism, calcifies coronary arteries and significantly increases cardiovascular disease. Randomized clinical trial evidence related to extraskeletal vitamin D outcomes was limited and generally uninformative. A recent recommendation on vitamin D dietary requirements for bone health is 600 IU/d for ages 1-70 years and 800 IU/d for 71 years and older, corresponding to a serum 25-hydroxyvitamin D level of at least 20 ng/ml (50 nmol/l). Further large randomized controlled trials are needed to reassess laboratory ranges for 25-hydroxyvitamin D in both diseases, in order to avoid under- and over-treatment problems, and completely clarify the relationship between atherosclerosis and osteoporosis.     

Osteoporosis,osteopenia, and atherosclerotic vascular disease

Older women with low bone mineral density (BMD) have a higher prevalence of atherosclerotic vascular disease (coronary artery disease, ischemic stroke, or peripheral arterial disease) than older women with normal BMD. Three coronary angiographic studies have shown that low BMD is associated with obstructive coronary artery disease. Low BMD has been shown to be associated with stress test-induced myocardial ischemia, reduced exercise capacity, and with aortic valve calcification. Women with osteoporosis have an increased risk for cardiovascular events. Treatment of osteoporosis or osteopenia should include therapeutic measures to prevent cardiovascular events.     

Vitamin D and menopause—A narrative review

There is accumulating evidence that vitamin D (VD) has important effects besides its well-known role in calcium and bone metabolism. Hypovitaminosis D is associated with cardiovascular disease, the metabolic syndrome, type 2 diabetes mellitus, cancer as well as with increased mortality. Further, VD deficiency is related to depression and impaired cognitive function. Increasing age and elevated body fat mass contribute to an increased risk of VD deficiency. Further, some studies report a relationship between VD and estrogen metabolism.     

Osteoporotic fractures: background and prevention strategies

Objectives: To review current knowledge of the epidemiology, pathogenesis, prevention and treatment of osteoporosis, with particular reference to issues related to the menopause. Methods: Peer-reviewed publications were assessed. Results: Much international variation exists in the prevalence of osteoporosis and the incidence of fracture. Risk fractures for osteoporosis are numerous. The menopause and other causes of hypogonadism in both women and men strongly predispose to osteoporosis. Various endocrinopathies, especially glucocorticoid excess, also are important. The contribution of family history may be explained by one or more genetic markers. Poor vitamin D and calcium nutrition, smoking, high alcohol consumption and inactivity increase risk. Reduced bone mass is a major risk factor for fracture, although the magnitude of that risk may vary between populations. In addition, bone fragility, length of the femoral neck (for hip fracture), history of prior fracture (for vertebral fracture) and falls affect fracture risk. Useful methods for measuring bone density are available for both epidemiologic surveillance and for clinical practice. Dual energy x-ray absorptiometry is the most desirable method in clinical care settings. Some risk factors can be modified for prevention of osteoporosis. Postmenopausal bone loss can be inhibited with estrogen or estrogen plus progestin therapy. Bone loss in the elderly may be moderated with calcium and vitamin D supplementation. Maintenance of muscle tone and strength through exercise may reduce falls. Conclusions: Osteoporosis is a large and growing health problem in many countries. Prevention of osteoporosis is a high priority, especially because treatment of the established disease remains sub-optimal. Prevention requires immediate, intermediate-term and long-term strategies. First line therapy for established osteoporosis in women in many countries is estrogen or estrogen plus progestin, calcium and vitamin D. Prospects for improved prevention of osteoporotic fractures are encouraging.     

High Prevalence of Vitamin D Deficiency in Adults Aged 50 Years and Older in Gwangju,Korea: the Dong-gu Study

Vitamin D plays an important role in bone metabolism and maintaining bone health. Recently, new evidence has revealed that vitamin D affects chronic diseases such as autoimmune diseases, cardiovascular diseases and certain cancers. The aim of this study was to evaluate the vitamin D status and the prevalence of vitamin D deficiency in an urban Korean population. This study included 8,976 participants (3,587 men and 5,389 women) aged 50 yr and older. Serum 25(OH)D level was measured by chemiluminescent microparticle immunoassay. The prevalence of vitamin D deficiency [25(OH)D < 20 ng/mL] was 59.7% and 86.5% in men and women, respectively. The prevalence of vitamin D deficiency increased significantly with age in men, but not in women and it decreased from April to July, more prominently in men than in women. These results suggest that sun exposure, intake of vitamin D supplement, and regular physical activities is recommended in an urban Koreans, especially in women.     

缓释阿托伐他汀钙纳米纤维支架对细胞黏附增殖的影响

文题释义：去溶剂化法：如果溶胶的溶剂化层和胶粒较强的结合力被破坏,则会导致两者的分离,胶体就会聚沉,这个过程就是去溶剂化过程,一般通过加热或者加入去溶剂化溶剂实现,乙醇是常见制备蛋白微粒的去溶剂化溶剂。 静电纺丝：是一种特殊的纤维制造工艺,高分子聚合物溶液或熔体在强电场中进行喷射纺丝。在电场作用下,针头处的液滴会由球形变为圆锥形(即“泰勒锥”),并从圆锥尖端延展得到纤维细丝,是高分子流体静电雾化的一种形式,在材料学领域已有较为广泛的应用。  摘要背景：他汀类药物在调节血脂、治疗和预防心脑血管疾病方面有显著作用,近些年研究发现他汀类药物在促骨形成及治疗骨质疏松方面具有一定的潜力。 目的：制备牛血清白蛋白微球及聚己内酯静电纺丝双重屏障缓释支架,用于药物阿托伐他汀钙的局部缓释,并探讨药物缓释支架对成骨细胞黏附及增殖的影响。 方法：采用去溶剂化法制备载阿托伐他汀钙的牛血清白蛋白微球,通过静电吸附作用在牛血清白蛋白微球表面包裹一层壳聚糖,达到增加微球稳定性的作用;将壳聚糖稳定的牛血清白蛋白微球纯化并冷冻冻干,备用。将微球冻干粉加入有机溶剂中充分溶解,再加入适当量纳米羟基磷灰石搅拌均匀,利用静电纺丝技术制作缓释阿托伐他汀钙纳米纤维支架,表征支架的微观形貌、降解性能与缓释性能。将缓释阿托伐他汀钙纤维支架与MC3T3-E1细胞共培养,观察细胞的黏附与增殖。结果与结论：①透射电镜显示,牛血清白蛋白纳米微球为规整的圆形,分散在静电纺丝中,其微球的基本形态得到保留;②扫描电镜显示,缓释阿托伐他汀钙纳米纤维支架的纳米纤维由直径均匀且表面连续光滑的丝构成,细丝交织形成网状结构;③缓释阿托伐他汀钙纳米纤维支架第1个月降解速度最快,后期降解速度减缓,降解3个月时材料已经不完整;④缓释阿托伐他汀钙纳米纤维支架有缓慢缓释药物的性能,时间长达1个月以上,总体释放类似零级动力学过程;⑤缓释阿托伐他汀钙纳米纤维支架可促进MC3T3-E1细胞的黏附与增殖;⑥结果表明,缓释阿托伐他汀钙纳米纤维支架具有良好的生物相容性,可促进成骨细胞的增殖与黏附。ORCID: 0000-0003-3316-061X(王乐) 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     

The importance of vitamin D in the pathology of bone metabolism in inflammatory bowel diseases

Etiological factors of bone metabolism disorders in inflammatory bowel diseases have been the subject of interest of many researchers. One of the questions often raised is vitamin D deficiency. Calcitriol acts on cells, tissues and organs through a vitamin D receptor. The result of this action is the multi-directional effect of vitamin D. The reasons for vitamin D deficiency are: decreased exposure to sunlight, inadequate diet, inflammatory lesions of the intestinal mucosa and post-gastrointestinal resection states. This leads not only to osteomalacia but also to osteoporosis. Of significance may be the effect of vitamin D on the course of the disease itself, through modulation of the inflammatory mechanisms. It is also necessary to pay attention to the role of vitamin D in skeletal pathology in patients with inflammatory bowel diseases and thus take measures aimed at preventing and treating these disorders through the supplementation of vitamin D.