IL-17在绝经后骨质疏松方面的相关研究

白介素-17(IL-17),CD4*细胞亚群Thl7细胞分泌的特征性细胞因子,在抵抗胞外细菌、真菌 感染的宿主防御以及各种自身免疫性疾病发病中起到了重要作用。绝经后骨质疏松现被认为可能是 一种炎症过程,现有研究表明IL-17在绝经后骨质疏松的发病机制中具有重要作用。本文综述了近 几年IL-17在绝经后骨质疏松相关研究中的研究进展,为后续相关研究提供理论支撑。     

Thl7细胞及相关因子IL-17与绝经后骨质疏松的相关性研究

目的 观察辅助性T细胞17 (T helper cell 17,Thl7)及及相关因子白细胞介素17( imerleukin 17,IL17)在绝经后骨质疏松（Postmenopausal osteoporosis, PMOP)患者外周血及血清中的表达水平,并探讨IL-17细胞与绝经后骨质疏松的发病的关系。方法 选取2011年7月?2014年7月在我院确诊的绝经后骨质疏松患者（60例）为研究组,选取同期来我院体检的绝经后骨量正常人群为对照组（60例）,采用流式细胞术检测绝经后骨质疏松患者及骨质正常人外周血中Thl7细胞水平,采用 ELISA法检测两组人群外周血中IL-17 、IL-6及TGF-β的蛋白水平;采用RT-PCR法检测两组人群外周血中转录因子T孤独核受体（retinoid-related orphan receptor gamma 1,RORγT)的mRNA水平。通过Pearson相关分析绝经后骨质疏松患者中IL-17水平与骨密度（bone mineral density,BMD)以及血清钙可能存在的关系。结果 绝经后骨质疏松患者外周血中Thl7细胞比例为 (2. 17 ±0.41)%,显著高于健康对照组人群的（0.61 ±0. 45)% ,差异有统计学意义（P <0.001);绝经后骨质疏松患者血清IL- 17水平（31. 51 ±10. 09)pg/mL,显著高于对照组人群的（16. 61 ±9. 93)pg/mL,差异有统计学意义（P <0. 001);绝经后骨质疏松患者外周血RORγTmRNA的表达水平显著高于正常人群,差异有统计学意义（P<0. 001)。绝经后骨质正常对照组人群外周血血清中IL-6及TGF-β水平均显著低于绝经后骨质疏松患者,差异有统计学意义(t=8. 99,P=0. 000;t = 4. 71 ,P = 0. 000); 此外,Pearson相关分析结果显示,绝经后骨质疏松患者血清中IL-17与BMD呈显著负相关（r =–0. 788 ,P<0. 05)。结论 Thl7 细胞可能通过分泌IL-17促进绝经后骨质疏松的产生,IL-17可能作为治疗绝经后骨质疏松的重要靶点。     

Fas/Fas-L信号系统在绝经后骨质疏松症中作用的研究进展

Fas/Fas-L信号系统是外源性凋亡通路的重要组成部分。近年来大量研究发现,Fas/Fas-L信号系统通过诱导细胞凋亡,不仅参与了免疫系统稳态的维持,而且在骨内环境稳态的调节中也发挥了重要的作用。Fas/Fas-L信号系统在不同骨细胞上的表达和分布可能随体内雌激素水平波动而发生变化。当绝经后雌激素分泌不足时,Fas/Fas-L信号系统可通过启动骨细胞外源性凋亡通路,介导成骨和破骨平衡向破骨方向偏移,参与绝经后骨质疏松症的发生发展。通过调节骨细胞上Fas/Fas-L信号系统来平衡破骨细胞骨吸收和成骨细胞骨形成,将为绝经后骨质疏松症的治疗提供新的思路。     

细胞因子配体3和绝经后骨质疏松症严重程度相关性研究

目的 探讨绝经后骨质疏松症患者血清细胞因子配体3(CCL3)水平是否与疾病严重程度相关。方法 82例绝经后骨质疏松症妇女,76例绝经后非骨质疏松症妇女,80例育龄健康妇女。采用双能X线骨密度仪测定全髋、股骨颈和腰椎L1-L4骨密度;使用商用酶联免疫吸附测定试剂盒检测血清CCL3水平;同时检测血清炎症细胞因子白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和1型交联的羧基末端端肽(CTX-1)和抗酒石酸酸性磷酸酶5b(TRACP-5b)。视觉模拟评分和OSwestry残疾指数评分用于评估临床严重程度。结果 绝经后骨质疏松症组患者血清CCL3水平明显高于绝经后非骨质疏松症组[(40.9±15.1) pg/mL vs (24.2±8.7) pg/mL,P＜0.001]和对照组[(40.9±15.1) pg/mL vs (23.9±9.1) pg/mL,P＜0.001]。血清CCL3水平与全髋(r=-0.345,P=0.002)、股骨颈(r=-0.329,P=0.003)和腰椎L1-L4(r=-0.354,P =0.001)的骨密度呈负相关,与视觉模拟评分(r=0.413,P＜0.001)和OSwestry残疾指数(r=0.360,P＜0.001)呈正相关。此外,血清CCL3水平与肿瘤坏死因子-α(r=0.305,P=0.005)、白细胞介素-6(r=0.288,P=0.008)、CTX-1(r=0.371,P＜0.001)和TRACP-5b(r=0.317,P=0.004)密切相关。在调整了体重指数和年龄后,所有的相关性仍然显著。结论 CCL3可能是一种有用的生物标志物,可用于预测绝经后骨质疏松症的病情严重程度。     

Bisphosphonates for postmenopausal osteoporosis

Bisphosphonates are effective in reducing bone turnover, increasing BMD and reducing fracture risk in postmenopausal women with osteoporosis. The licensed bisphosphonates exhibit some differences in potency and speed of onset and offset of action. These differences mean that different agents may be more advantageous in different situations. Uncertainties still exist around the optimum duration of treatment and treatment holidays, how best to use bisphosphonates with anabolic treatments, and the benefits of treatment in patients who do not have a BMD T-score below -2.5.     

Variations in treatment of postmenopausal osteoporosis

The purpose of this study was to determine trends and differences between various medical specialties with regard to the treatment of postmenopausal osteoporosis. The method used was a cross-sectional survey, and the authors' sample was composed of 116 physicians. There was an overall lack of consensus on choice of treatment for postmenopausal osteoporosis. Treatment varies with the individual physician without any strict adherence to a formal therapeutic protocol. Calcium was the treatment modality most widely used by all the specialties. Gynecologists and endocrinologists show the greatest usage of estrogens, while orthopedic surgeons show the least. Fluoride was used significantly less than calcium, vitamin D, estrogen, diet, and exercise by all the specialties surveyed. One in three postmenopausal women in the United States has osteoporosis, and one in five will sustain a hip or vertebral fracture. Twelve to twenty percent of elderly patients die within six months of sustaining a hip fracture. There is an obvious need for carefully constructed clinical programs evaluating multiple agents and diagnostic techniques.     

绝经后骨质疏松症治疗的研究进展

骨质疏松症是一种多发于妇女绝经后的骨疾病,其预防、治疗已是当前许多国家重要保健课题之一。笔者主要就近几年来国内外治疗绝经后骨质疏松症的方法,分别从中药、西药和非药物治疗三方面做一综述。目前3种治疗方法均能取得较好的疗效,但都存在一定的问题,需要更深入地开发、研究中药和西药,探索有效而安全的个体化治疗方案,将两者结合起来,辅以非药物治疗,实行优势互补。     

绝经后妇女骨质疏松侯选基因ER、IL-6、COLIA1的研究

目的　骨质疏松是一种多基因疾病 ,本研究目的是探讨绝经后妇女的雌激素受体(ER)、白介素 6 (IL 6 )和Ⅰ型胶原α1(COLIA1)基因多态性与骨密度等指标的关系。方法　用DEXA检测 2 0 5例绝经后妇女的腰椎和股骨颈骨密度 ,用PCR RFLP方法检测ER基因PvuII和XbaⅠ多态性和Ⅰ型胶原α1(COLIA1)基因多态性 ;PCR扩增IL 6基因 3’端非翻译区的多态性区域。结果　ER基因PP、Pp和pp基因型频率分别为 13 7%、5 1 2 %和 35 1% ,pp型的绝经后妇女股骨颈骨密度Z值明显高于Pp型。ER基因XX、Xx和xx基因型分别占 6 8%、2 5 9%和 6 7 3%。XX基因型的妇女虽然停经时间更长 ,但腰椎骨密度仍高于Xx和xx型。发现了D/D、D/E、C/D、C/C和E/E5种IL 6基因型 ,93%以上的绝经后妇女属于D/D和D/E型。在绝经 10年以上的妇女中 ,D/E型的腰椎骨密度明显高于D/D型 ,且前者的体重指数更高。所有样本的COLIA1基因型检测结果都是无突变的纯合子SS。结论　ER基因型中的pp和XX型可能分别对股骨颈和腰椎有保护作用 ;IL 6基因多态性与停经时间较长的绝经后妇女腰椎骨密度有一定关系 ;COLIA1基因型可能不适于评估本地区绝经后妇女骨密度的差异。这些骨质疏松候选基因的意义尚有待在不同种族的人群进行更大样本的研究     

Placebo therapy for postmenopausal osteoporosis

Eighteen postmenopausal osteoporotic (PMO) women on placebo therapy were followed for 1 year. Serial measurements of calcium balance and kinetics, bone histomorphometry, photon absorptiometry, and radiogrammetry were obtained. Few significant changes in balance and kinetics or bone histology were seen in these women over time. Photon absorptiometry and radiogrammetry of the femoral cortex showed a significant annual bone loss however. When compared with premenopausal and healthy postmenopausal women, the annual bone loss in those with PMO was significantly greater. The ability of balance studies, photon absorptiometry, and radiogrammetry to predict the magnitude of this bone loss was similar. Finally, there was an illustration of the use of the estimated variance provided by this study for estimating sample size for future studies.     

丹参酮防治绝经后骨质疏松症

选择45-74岁、绝经1～25年的妇女6l例，对照组28例．用具有雌激素样活性的中药丹参酮治疗．对照组用尼尔雌醇治疗．同时补充钙剂。分别于治疗前后检测血清雌二醇(E2)血清碱性磷酸酶(AKP)、骨钙素(BGP）、尿钙(u-Ca)尿肌酐(UCr)及尿羟脯氯酸(U-Hpt)。结果表明：治疗组服药后AKP、BGP、尿Ca／Cr及Hpr／Cr明显低于治疗前(P＜0．05)。E2治疗前后无差异。提示丹参酮和尼尔雌醇均有抑制骨吸收及降低骨转换率延缓或阻断绝经后快速骨丢失的作用。     

绝经后妇女骨质疏松症的治疗进展

近年来,骨质疏松症治疗的研究进展发展很快。本文针对绝经后妇女的骨质疏松症,从诊疗方案的设计原则到具体药物的治疗进展进行综述。     

绝经后骨质疏松的骨免疫学机制

绝经后骨质疏松是雌激素缺乏引起骨形成与骨吸收解耦联,导致骨吸收大于骨形成,进而引起骨量减少,一般表现为骨密度的降低及骨微结构的破坏,最终骨脆性增加易于骨折。随着我国社会经济的发展,人口老龄化日益增加,绝经后骨质疏松的患病率也日趋上升,给患者家庭及社会医疗带来了极大的挑战。绝经后骨质疏松被认为是一种慢性低度炎症的全身性疾病。雌激素缺乏使得B细胞及T细胞被激活,激活的淋巴细胞分泌TNF-α、IL-17、IL-6及RANKL等促骨吸收因子促进破骨细胞骨吸收。目前认为雌激素缺乏导致的骨丢失与趋化因子、免疫细胞及其分泌的细胞因子密切相关,即绝经后骨质疏松的骨免疫学机制。     

社区绝经后妇女骨质疏松症的健康教育

目的 普及和加强社区内绝经后妇女对骨质疏松的认知和预防.方法 我科于2015年6月至2016年5月对来自广东省深圳市罗湖区社区的802名绝经骨质疏松妇女进行社区教育,年龄为52~69岁,平均为(60.0±8.9)岁.教育内容包括:①骨质疏松症的知识;②合理饮食和营养;③加强身体锻炼;④保持规律生活和健康习惯;⑤防治剧烈的肢体冲击和配备拐杖.结果 802名绝经骨质疏松妇女在经过关于骨质疏松的普及教育后,情况均有所好转:①骨质疏松诊断标准认知率由11.97%提高到69.82%(P<0.05);②预防认知率从14.96%提升到87.78%(P<0.05);③治疗方法认知率由4.98%提高到60.84%(P<0.05);④对危险因素的意识由9.97%提高到78.80%(P<0.05);⑤社区妇女在饮食营养、锻炼、规律服药和自我保护(配拐杖)等认知均有显著变化(P<0.05).结论 本研究的社区教育取得了较好的效果.今后应加强社区教育,科学的认知、预防和治疗骨质疏松,提高骨质疏松绝经后妇女的生存质量.     

IL-33与绝经后骨质疏松女性骨密度和骨代谢指标相关性研究

目的 探索血清白细胞介素-33(IL-33)与绝经后骨质疏松女性骨密度和骨代谢指标相关性。方法 采用酶联免疫吸附法测定50例绝经后骨质疏松患者和50例正常绝经后妇女血清IL-33水平。采用双能X线骨密度仪(DXA)测量患者和对照组的骨密度(BMD)。检测维生素D、钙、碱性磷酸酶(ALP)、甲状旁腺激素(PTH)水平,以及1型胶原C末端肽(CTX)和1型前胶原N端前肽(P1NP)等骨转换指标。结果 在绝经后骨质疏松症女性中,IL-33水平显著低于健康对照组[(3.53±2.45) pg/mL vs (13.72±5.39) pg/mL,P=0.007];Spearman相关分析表明血清IL-33水平与年龄、BMI、PTH、CTX和P1NP水平呈负相关,与腰椎BMD和股骨颈BMD呈正相关。多元回归分析表明,年龄、BMI、腰椎BMD、PTH、股骨颈BMD和血清CTX和P1NP水平是骨质疏松症患者血清IL-33水平降低的独立预测因子。结论 血清IL-33降低是绝经后骨质疏松患者股骨颈和腰椎骨密度降低和骨转换增速的危险因素。     

Long-term fluoride therapy of postmenopausal osteoporosis

The benefit of sodium fluoride (NaF) in the therapy of osteoporosis is still controversial. For 3 years we monitored patients with postmenopausal osteoporosis subjected to a continuous treatment with 80 mg NaF/day and patients without fluoride treatment. Every 3 months peripheral total and trabecular bone densities were evaluated with high-precision low-dose quantitative computed tomography, every 6 months biochemical parameters were measured, and every year new crush fractures were determined. The untreated osteoporotics as a group lost bone at a rate of 2.5%/year. In the fluoride-treated group trabecular bone density of the distal tibia remained unchanged in 5 of 15 treated patients; 2 patients experienced a bone loss, 8 patients showed at least a temporary bone gain. After 3 years trabecular bone density of the treated patients was 8% higher than that of the untreated patients. Total bone density was not increased. The fracture rates in a group of untreated and a group of NaF-treated patients matched with regard to age, height, weight, initial fracture rate, and initial trabecular bone density were significantly different in the first year, with 0.3 new fractures in the untreated group and 2.9 new fractures in the treated group. During the second and third year the mean number of new fractures was approximately equal in both groups. In 47% of the treated patients, osteoarticular side effects were observed. In 27%, scintigraphy of the ankle was positive, alkaline phosphatase was increased, and radiologic signs of healing stress fractures were present.(ABSTRACT TRUNCATED AT 250 WORDS)     

绝经后骨质疏松小鼠模型肝脏铁调素表达增加

目的 观察去卵巢小鼠铁代谢及铁调素表达量的改变,探讨铁代谢紊乱在绝经后骨质疏松中的作用机制。方法 16w龄雌性C57BL/6小鼠分为双侧去卵巢手术（OVX组）和假手术（SHAM组）两组,6w后处死,取血清、子宫、肝脏、脾脏、股骨等组织。检测股骨生物力学指标、血清骨代谢标志物、血清铁及肝脾铁的水平,肝脏铁调素的表达采用PCR技术进行检测。结果 与SHAM组相比,OVX组股骨最大弯曲应力及弹性模量降低,血清骨钙素降低,1型胶原C端肽升高,同时,血清铁降低,肝脾铁含量升高,肝脏铁调素表达升高。结论 雌激素不足增加铁调素的表达,导致组织内铁过载,与绝经后骨质疏松的发生发展有密切联系。