PM2.5对绝经后骨质疏松症影响的作用机制

绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)是原发性骨质疏松症的一种类型,是绝经后妇女的常见病及多发病,主要因女性在绝经后卵巢功能减退、雌激素水平明显下降,导致骨生成和骨吸收代谢失衡,容易发生骨折等并发症。国外有研究显示大气细颗粒物(PM2.5)与骨质疏松症的发生有关。PM2.5可通过影响绝经女性骨代谢的炎性效应机制、受体竞争机制、雌孕激素受体机制等,使骨形成和骨吸收代谢失衡,直接或间接引发或加剧PMOP。但PM2.5是否参与PMOP的发生及进展,其作用机制如何尚未明确,本文就PM2.5与PMOP的相关性及作用机制进行综述。     

雌激素影响绝经后骨质疏松分子机制研究进展

<正>骨质疏松是以骨量减少、骨的微观结构退化为特征的,致使骨的脆性增加以及易于发生骨折的一种全身性骨骼疾病,可分为三大类即原发性骨质疏松、继发性骨质疏松、特发性骨质疏松。绝经后骨质疏松(PMOP)为Ⅰ型原发性骨质疏松,由绝经后机体雌激素水平下降而引发,年龄通常界定在50~70岁。雌激素的缺乏被认为是PMOP的主要原因,其中具体的分子机制仍未达成共识,本文结合近些年研究雌激素对PMOP发病机     

绝经后骨质疏松症患者血清miR-21和Smad7表达变化及其临床意义

目的 探讨绝经后骨质疏松症(PMOP)患者血清微小RNA-21(miR-21)、Smad同源物7(Smad7)表达变化及其临床意义.方法 选择PMOP患者40例(骨质疏松组)、绝经后骨密度降低患者40例(骨密度降低组)、绝经后骨密度正常健康志愿者40例(骨密度正常组),采集清晨空腹肘静脉血,离心留取血清,检测血清miR...     

山茶籽油与不同雌激素受体-β基因型交互作用对广西百色壮族妇女绝经后骨质疏松的影响

目的探讨山茶籽油对不同雌激素受体(ER)-β基因型广西百色壮族妇女绝经后骨质疏松(PMOP)的影响。方法598名长期食用山茶籽油(ECO)的广西百色壮族绝经妇女为ECO组,619名长期不食用ECO的广西壮族绝经妇女为NECO组,用超声骨质密度仪测量两组右侧跟骨超声骨质密度(BUA),用限制性片段长度多态性聚合链反应(PCR-RFLP)检测两组ER-β基因多态性。结果 ECO组PMOP患病率明显低于NECO组(P0.05)。两组ER-β的RsaⅠ酶切rr基因型分布频率差异有统计学意义(P0.05),rr基因型PMOP患病率明显增多(P0.05)。ECO PMOP组携带AluⅠ酶切位点的Aa基因型分布频率明显少于NECO PMOP组(P0.05)。结论 ECO对PMOP有防治作用;ER-β的rr基因型可能是PMOP的遗传易感基因;ER-β的Aa基因型是与山茶籽油起交互作用对PMOP防治的敏感基因型。     

生活方式调整预防老年绝经后骨质疏松的研究进展

<正>绝经后骨质疏松(PMOP)导致的骨折可引起妇女预期寿命缩短、生活质量降低,并大大增加患者及全社会的医疗负担。各种防治PMOP的措施中,生活方式调整因为其经济、实用、安全且有效的特点,一直被国内外学者持续研究并予以完善。本文就近年来该内容的研究新进展做一综述。1饮食习惯1.1高钙饮食作为组成骨骼的重要成分,钙质的足量摄入对于维持骨量的重要性无可争议。然而,由于绝经后妇女雌激     

雌激素替代治疗防治绝经后骨质疏松症的研究

雌激素替代治疗 (ERT)是绝经后骨质疏松症的首选治疗方案。ERT的作用机制尚不完全清楚 ,除通过钙调节激素间接起作用外 ,还可通过雌激素受体 (ER)直接调节成骨细胞 (OB)和破骨细胞 (OC)的增殖、分化或活性 ;也可通过抑制或促进细胞因子或生长因子的生成起作用 ;还可通过抑制OB和骨细胞的凋亡 ,促进OC的凋亡发挥作用。此外 ,新近提出雌激素可降低骨髓的信号强度阈值有利于在靠近骨髓的骨组织启动保存方式骨重建而保留骨组织。开展ERT的机制研究将为绝经后骨质疏松 (PMOP)的发病机制研究和预防、治疗开辟广阔的领域     

QUALEFFO-41量表调查分析影响西安市绝经后妇女骨质疏松患者生活质量的因素

目的调查影响绝经后骨质疏松症(Postmenopausal Osteoporosis,PMOP)患者生活质量(Quality of life,QOL)及主要因素,以便预防和减少本病的发生,以提高整个PMOP人群的QOL。方法对111例绝经后骨质疏松症患者(45-90岁)QOL及影响因素的测量采用QUALEFFO-41量表结合肖建德编著的《实用骨质疏松学》中的骨质疏松症病史采集表进行测评。结果本次研究中PMOP患者QOL水平较低,QOL总评分为(288.420±14.668)。评分越低,代表QOL越好。单因素方差分析显示年龄、文化程度、职业、婚姻状况、体质指数(Body Mass Index,BMI)、有无喝咖啡、有无喝牛奶、绝经年限、既往病史、运动史(近5年)、运动频率以及有无骨折史是影响PMOP患者QOL的因素(P0.05)。通过多元线性回归分析,按照影响QOL评分因素的作用强度由高到低依次是运动史(近5年)、BMI、职业、婚姻状况、既往病史、有无喝牛奶、运动频率、绝经年限。结论调查显示PMOP患者的QOL总体水平较低。因此应改善骨痛等症状,均衡饮食,改变不良生活习惯,适量运动,获得家庭、社会支持,加强心理疏导,积极参加社会活动,以提高患者的QOL。     

骨细胞程序性坏死对绝经后骨质疏松症患者脆性骨折的影响

目的 明确绝经后骨质疏松(postmenopause osteoporosis, PMOP)脆性骨折患者骨细胞是否发生程序性坏死,探讨骨细胞程序性坏死对PMOP患者脆性骨折的影响,进一步完善PMOP的发病机制。方法 收集2020年1月至2021年1月于海南医学院第一附属医院PMOP股骨颈脆性骨折患者的临床病例资料和骨组织标本。采用TUNEL+受体相关蛋白激酶(receptor interaction protein kinase, RIP)3免疫荧光检测骨组织中发生程序性坏死的骨细胞数量,免疫荧光和免疫组化检测程序性坏死标志性蛋白RIP1/3、混合谱系激酶配体(mixed lineage kinase domain-like, MLKL)及凋亡标志性蛋白cleaved caspase-3的表达,并比较两组间的差异,透射电镜观察骨细胞的形态学改变,micro-CT重建股骨颈Ward’s三角骨组织微结构;采用Pearson相关性检验分析骨细胞程序性坏死率与骨组织微结构的相关性。结果 免疫荧光和免疫组化显示：PMOP股骨颈脆性骨折患者RIP1、RIP3、MLKL、cleaved caspas...     

基于肾主骨生髓探讨骨髓基质干细胞与绝经后骨质疏松肾虚证的关系

<正>绝经后骨质疏松(PMOP)是骨量减少导致骨微结构改变骨折发生率增加的一种绝经后女性常见的骨代谢疾病。《黄帝内经》提出"肾主骨髓"的理论,从生理上详细描述了女子骨的强弱与肾气盛衰的关系,从病理上提出了肾虚骨痿的理论。骨髓基质干细胞具有骨向分化的潜能,与女子骨的强弱关系密切。补肾中药能通过特发性促性腺激素低下(IHH)信号通路刺激骨髓基质干细胞向成骨细胞生长,从而改善女性PMOP,提示     

环状RNA hsacirc0001445在绝经后骨质疏松症患者中的表达及作用机制

目的探讨环状RNA(circRNA)hsa_circ₀001445在绝经后骨质疏松症(PMOP)患者中的临床意义和调控机制。方法从临床收集的血液样品中提取RNA, 使用实时荧光定量PCR(qRT-PCR)检测hsa_circ₀001445的表达。荧光素酶报告基因分析、RNA下拉实验研究了RNA之间的相互作用。结果与健康对照组相比, PMOP患者血浆hsa_circ₀001445表达下调(P<0.001)。血浆中hsa_circ₀001445以高灵敏度和特异性将PMOP患者与健康对照组区分开来, 曲线下面积(AUC)为0.9654(95%CI0.9361～0.9947, P<0.001), 灵敏度为94.0%, 特异度为88.0%。Hsa_circ₀001445促进人骨髓间充质干细胞(hBMSCs)的成骨分化、抑制成脂分化(P<0.001)。Hsa_c     

Ethnic difference in contribution of alleles of the interleukin-1 receptor antagonist gene to predisposition to osteoporosis

Background:  The interleukin-1 receptor antagonist (IL-1RA) plays an important role in bone metabolism, and molecular defects are implicated in the pathogenesis of osteoporosis. Studies performed in Caucasian populations have demonstrated an association between allelic variants of the IL-1RA gene and bone mineral density (BMD).
Methods: In the study reported here, we examined whether variation of the IL-1RA gene would correlate with osteoporosis among 287 Japanese postmenopausal women.
Results:  The allele frequencies and distribution in this ethnic group were remarkably different from those reported for Caucasians and phenotypes such as Z scores of lumbar spine (L2–4) and total body BMD, as well as various biochemical markers related to bone metabolism, were not significantly different among groups of IL-1RA genotypes in the present study.
Conclusion:  Our results emphasize the importance of considering ethnic background in assessing the etiological significance of candidate genes in osteoporosis.     

The use of parathyroid hormone in the treatment of osteoporosis

Anabolic skeletal agents have recently broadened our therapeutic options for osteoporosis. By directly stimulating bone formation, they reduce fracture incidence by improving bone qualities in addition to increasing bone mass. Teriparatide [recombinant human parathyroid hormone(1–34)], the only anabolic agent currently approved in the United States for osteoporosis, has emerged as a major therapeutic approach to selected patients with osteoporosis. Teriparatide is approved for both postmenopausal women and men with osteoporosis who are at high risk for fracture. With the use of this anabolic agent, bone density and bone turnover increase, microarchitecture improves, and bone size is beneficially altered. The incidence of vertebral and nonvertebral fractures is reduced with teriparatide use. Combination therapy with parathyroid hormone and an antiresorptive does not appear to offer definitive advantages over the use of PTH or an antiresorptive alone, although recent ideas about combining these agents may offer new insights. In order to maintain increases in bone density acquired during PTH therapy, it is important to follow its use with an antiresorptive agent.     

Possible pathogenetic role of new cytokines in postmenopausal osteoporosis and changes during calcitonin plus calcium therapy

The present study was designed to test if the serum cytokines (interleukin, or IL-1beta, -2, -2r, -6, -6r, -8, and -10, and tumor necrosis factor alpha, or TNF-alpha) and osteocalcin levels were different between 50 osteoporotic and 30 postmenopausal nonosteoporotic women and to evaluate the efficacy of calcitonin therapy during 6 months on serum cytokines and osteocalcin levels in postmenopausal osteoporotic women. In our study, serum levels of osteocalcin, TNF-alpha, IL-2, and IL-8 were significantly higher in the patient group (P < 0.05), whereas serum levels of IL-10 and IL-6r were significantly lower in the patient group (P < 0.05). When analysed separately according to bone turnover, serum levels of IL-10 and IL-6r were significantly lower in the normal-turnover group (P < 0.05), and IL-2, IL-8, and TNF-alpha were significantly higher in the high-turnover group than in the control group (P < 0.05). Statistically significant improvement seemed to happen in the patients receiving calcitonin plus calcium therapy (P < 0.05) concerning levels of serum IL-6r at the 1st month (P < 0.05), IL-10, IL-2r, IL-6r, and osteocalcin at the 3rd month, and IL-6r and osteocalcin at the end of the 6th month. Our findings demonstrate that calcitonin plus calcium therapy appears to be particularly more effective for patients with high turnover. In addition, our study suggests that IL-10 and IL-6r may have an important role in normal-turnover osteoporosis, while IL-2, IL-8, and TNF-alpha may play an important role in high-turnover postmenopausal osteoporosis.     

Ovarian steroid treatment blocks a postmenopausal increase in blood monocyte interleukin 1 release.

In previous studies, we showed that blood monocyte elaboration of interleukin 1 (IL-1), a known stimulator of bone resorption, was higher in osteoporotic patients with rapid bone turnover than in those with slow turnover and in nonosteoporotic subjects. Since an acceleration of bone loss following menopause contributes to the risk of osteoporosis in women, we have studied the effects of menopause and ovarian steroid treatment on IL-1 release by monocytes obtained from nonosteoporotic and osteoporotic women. IL-1 activity in the monocyte culture medium derived from untreated postmenopausal women (nonosteoporotic and osteoporotic) was higher than in the medium derived from either untreated premenopausal or estrogen/progesterone-treated postmenopausal women. A significant negative correlation was found between IL-1 and years since menopause in both the healthy (r = -0.75; P less than 0.005) and the osteoporotic (r = -0.61; P less than 0.01) untreated postmenopausal women. The difference between the two slopes was significant at P less than 0.05. Premenopausal IL-1 levels were achieved within 8 years of menopause in the nonosteoporotic, but not in the osteoporotic, subjects in whom increases were evident as long as 15 years after menopause. IL-1 also correlated inversely with vertebral mineral density (r = -0.37; P less than 0.05), as measured by quantitative computed tomography. In prospective studies, treatment with estrogen/progesterone for 1 month caused a substantial highly significant decrease in IL-1 activity in each of three nonosteoporotic and five osteoporotic women, confirming the apparent effect of hormone therapy observed in the cross-sectional analysis. Although a cause-effect relationship has not been established, it is our hypothesis, based on these data, that alterations in IL-1 production may underlie the postmenopausal acceleration in bone loss and its inhibition by ovarian steroids. Persistent elevation of IL-1 secretion appears to be a feature of postmenopausal osteoporosis.     

Upregulation of hepcidin by interleukin-1beta in human hepatoma cell lines.

Anemia of chronic disease (ACD) is commonly observed in chronic inflammation, although its pathogenesis is poorly understood. Hepcidin is thought to be a key regulator in iron metabolism and has been implicated in ACD. Although the induction of hepcidin by an inflammatory cytokine interleukin-6 (IL-6) seems to have been confirmed, it is still controversial whether interleukin-1beta (IL-1beta), also known as an inflammatory cytokine, regulates hepcidin expression. We demonstrated that hepcidin mRNA was upregulated by IL-1beta in human hepatoma-derived HuH-7 cells, particularly at low concentrations of IL-1beta, while high concentrations of IL-6 were needed for the upregulation of hepcidin mRNA. Therefore, IL-1beta might be more important for the upregulation of hepcidin in physiological conditions than IL-6. Although IL-1beta induces IL-6 production in hepatocytes, our data indicate that the effect of IL-1beta on hepcidin expression is independent from that of IL-6. In conclusion, IL-1beta might have an important role in ACD.     

Effects of estrogen in vivo and in vitro on spontaneous interleukin-1 release by monocytes from postmenopausal women

Estrogen (E) inhibits bone resorption, but the mechanism of this effect is unknown. Interleukin-1 (IL-1) stimulates bone resorption in vitro and may be produced in bone by mononuclear phagocytes. Recently, the spontaneous release of IL-1 from peripheral monocytes was found to reflect bone formation in a subset of patients with idiopathic osteoporosis. We suspected that the action of E on bone is mediated indirectly by its effect on monocyte IL-1 activity. Eleven normal postmenopausal women taking no medications were given conjugated E (0.625 mg daily) for 3-9 weeks. Supernatants from cultured peripheral monocytes were analyzed for IL-1 production by stimulation of a cloned murine helper T-cell line. IL-1 release was expressed as a percentage of maximum release corrected for monocyte number. IL-1 release before E treatment was 11.0 +/- 0.2% (+/- SE), it was 7.8 +/- 1.6% after E treatment (P = NS). IL-1 release fell in each of the three women with the highest initial values (46% to 5%, 25% to 17%, and 18% to 12%). IL-1 release did not correlate with serum osteocalcin or fasting urinary calcium either before or after E treatment. Addition of 10(-7)-10(-10) mol/L 17 beta-estradiol to cultured monocytes obtained before E treatment caused an increase in IL-1 release that did not follow a dose-response relationship. Treatment of postmenopausal women with E did not affect spontaneous IL-1 release by peripheral monocytes in vitro. The addition of E in vitro did not produce consistent changes in IL-1 release by these cells. This does not exclude the possibility that E may affect monocyte IL-1 release in subsets of women with high spontaneous monocyte IL-1 release with or without osteoporosis.     

中波紫外线照射治疗绝经后骨质疏松的临床研究

目的 探讨中波紫外线照射仪对绝经后骨质疏松的治疗作用.方法 选择符合诊断标准的绝经后骨质疏松患者99例随机分为A、B、C三组,在A组35例肾阳虚型绝经后骨质疏松患者用中波紫外线照射治疗;B组34例肾阴虚型绝经后骨质疏松患者用中波紫外线照射治疗,两组均加服钙剂(2 g/ d).对照组C组,30例绝经后骨质疏松患者肌注鲑鱼降钙素,同时加服钙剂 (2 g/ d).观察治疗前后血清1,25(OH)2D3、Young Z、腰椎骨密度(BMD)的变化.结果 中波紫外线照射治疗肾阳虚组血清1,25(OH)2D3、Young Z、腰椎BMD在治疗前后差异均有显著性,与肾阴虚组比较有显著差异.C组各观察指标无明显变化.结论 中波紫外线照射对绝经后肾阳虚型骨质疏松有较好的疗效,可提高骨密度,改善骨代谢.     

Comparison of the effect of alendronate on lumbar bone mineral density and bone turnover in men and postmenopausal women with osteoporosis

The purpose of the present study was to compare the effect of alendronate treatment on lumbar bone mineral density (BMD) and bone turnover in men and postmenopausal women with osteoporosis. Sixty men with primary or secondary osteoporosis and 318 women with postmenopausal osteoporosis were treated with alendronate. The primary end points were lumbar BMD and urinary cross-linked N-terminal telopeptides of type I collagen (NTX) and serum alkaline phosphatase (ALP) levels. The secondary end point was the incidence of vertebral and nonvertebral fractures. Forty-seven (78.3%) men and 254 (79.9%) women who could complete the 12-month trial were analyzed. The mean ages of men and postmenopausal women were 69.1 and 70.4 years, respectively. Both men and postmenopausal women showed higher levels of urinary NTX as compared with normal range of premenopausal women. Alendronate treatment decreased urinary NTX level by 39.2% in men and 45.4% in postmenopausal women at 3 months and serum ALP level by 17.8 and 21.0%, respectively, at 12 months. Following reduction in bone turnover markers, lumbar BMD increased 5.8 and 7.6% in men and postmenopausal women, respectively, at 12 months. Reduction in urinary NTX level and increase in lumbar BMD were smaller in men than in postmenopausal women. The incidence of vertebral and nonvertebral fractures was 10.6 and 8.5%, respectively, in men and 8.3 and 7.5%, respectively, in postmenopausal women, with no significant difference in these incidences between them. These results suggested that alendronate treatment effectively increased lumbar BMD from baseline in men with primary or secondary osteoporosis following reduction in bone turnover, although its efficacy did not appear to be greater than in postmenopausal women with osteoporosis. We have no funding sources; we have no conflict of interest.     

Association of tumor necrosis factor receptor 1 gene polymorphism with bone mineral density

Background:   Estrogen deficiency in postmenopausal women causes an increased production of proinflammatory cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α. These cytokines are associated with an increase of bone turnover and an acceleration of bone loss. Tumor necrosis factor-α is known to promote osteoclastogenesis via TNFR1, one of the tumor necrosis factor receptors (TNFR). Therefore, the purpose of the present report was to investigate the association of TNFR1 gene polymorphism with bone mineral density (BMD) in postmenopausal Japanese women.
Methods:   The question of whether a polymorphism of the TNFR1 gene would correlate with osteoporosis in 320 unrelated healthy postmenopausal women in Japan, was investigated. A single nucleotide polymorphism (SNP) located at Pro12 (CCA to CCG) in exon 1 of TNFR1 was utilized.
Results:   The subjects were categorized into three genotypes: AA, AG, and GG. The frequency of each genotype was 72.2%, 23.8%, and 4.0%, respectively. The association of this polymorphism with BMD of the lumbar spine and total body, and several bone metabolic markers was then examined. Concerning the TNFR1 gene, the AA group had significantly low total body BMD, compared with the AG + GG group (Z score; 0.285 vs 0.568; P  = 0.03), although BMD of the lumbar spine was not statistically different.
Conclusion:   These results suggest an association between this SNP of the TNFR1 gene and BMD, and an involvement of TNFR1 in postmenopausal osteoporosis among Japanese.