骨质疏松中的自噬相关信号通路

骨质疏松症（osteoporosis，OP）是以全身性骨量的丢失、骨微观结构的退行性改变为特征的骨骼疾病，根本原因在于成骨细胞和破骨细胞的动态平衡失调。自噬（Autophagy）能够通过影响成骨和破骨细胞分化的过程改变两者的平衡关系，这就提示我们可以从调控自噬的角度对骨质疏松的病情发展进行干预。本文就自噬的信号通路在骨质疏松症方面的研究进展进行综述，希望为进一步探究自噬信号通路的内在调控机制，选择适当的干预靶点，选择性发挥自噬对成骨、破骨细胞的调节作用，为临床上治疗骨质疏松症提供新的思路。     

A meta-analysis of the secondary fractures for osteoporotic vertebral compression fractures after percutaneous vertebroplasty

To identify the risk factors of the secondary fractures for osteoporotic vertebral compression fractures (OVCFs) after percutaneous vertebroplasty (PVP).We conducted a search of relevant articles using Cochrane Library, PubMed, Medline, Science Direct, Embase, the Web of Science and other databases. The time range we retrieved from establishment of the electronic database to November 2017. Gray studies were found in the references of included literature reports. STATA version 11.0 (Stata Corporation, College Station, Texas) was used to analyze the pooled data.Fourteen studies involving 1910 patients, 395 of whom had fracture secondary to the surgery were included in this meta-analysis. The result of meta-analyses showed the risk factors of the secondary fractures for OVCFs after PVP was related to bone mineral density (BMD) [95%CI (−0.650, −0.164), SMD=−0.407, P=.001], cement leakage ((RR=0.596, 95%CI (0.444,0.798), P = .001)), and kyphosis after primary operation ((SMD=0.741, 95%CI (0.449,1.032), P = .000)), but not to gender, age, body mass index, cement volume, thoracolumbar spine, and cement injection approaches.Bone mineral density, cement leakage, and kyphosis after primary operation are the risk factors closely correlative to the secondary fracture after PVP. There have not been enough evidences to support the association between the secondary fracture and gender, age, body mass index, cement volume, thoracolumbar spine, and cement injection approaches.     

唑来膦酸对芳香化酶抑制剂辅助治疗乳腺癌患者骨密度的影响

目的观察唑来膦酸对芳香化酶抑制剂辅助治疗乳腺癌患者骨密度的影响。方法前瞻性评估了102例绝经后临床激素受体阳性乳腺癌I-III A期患者术后12个月内腰椎和双侧股骨颈的骨密度(bone mineral density,BMD)改变。患者术后接受芳香酶抑制剂作为辅助治疗且患有骨质疏松症(腰椎或双侧股骨颈BMD,相当于T值分类≤-2. 5)的女性。患者12个月内接受补充钙、维生素D和5 mg静脉注射唑来膦酸治疗。结果腰椎骨密度在6个月和12个月时分别增加了4. 9%和6. 6%。右股骨颈和左股骨颈的BMD分别为3. 3%和4. 1%。在该研究中未观察到低钙血症、颌骨坏死和非创伤性临床骨折。结论本研究表明,接受佐剂芳香酶抑制剂治疗的妇女接受一次唑来膦酸治疗后BMD大幅增加,无论其芳香酶抑制剂治疗的历史如何。     

补肾中药诱导骨髓间充质干细胞增殖分化防治骨质疏松的研究进展

骨髓间充质干细胞(Bone marrow mesenchymal stem cells,BMSCs)是干细胞研究领域的热点。BMSCs增殖分化成成骨细胞与中医"肾藏精"理论有一定联系,应用补肾中药干预BMSCs增殖分化防治OP具有良好研究的前景。从中医"肾藏精"理论与BMSCs的关系以及补肾中药(单味中药与单体,中药复方)两个方面,对近年来补肾中药诱导BMSCs增殖分化防治OP的研究进展进行了综述。     

地舒单抗在类风湿性关节炎中的应用

骨质疏松是类风湿性关节炎的常见并发症。地舒单抗是一种可与核因子kappa-B 受体激动剂配体结合 的全人源性单克隆抗体，能抑制破骨细胞活性，增加骨密度，减少骨折发生率，并且安全性良好。地舒单抗越来越 多的用于类风湿性关节炎的治疗。地舒单抗可以增加类风湿关节炎患者的骨密度，阻止骨侵蚀和关节周围骨质 流失的发生，降低骨折的发生率，但不影响滑膜炎症和关节活动度。地舒单抗与治疗类风湿性关节炎的药物联合 应用可协同抑制骨侵蚀，且耐受性良好，感染的发生率并未增加，同时需关注颌骨坏死和非典型股骨骨折等罕见 副作用，建议补充维生素D 及钙剂预防低钙血症。地舒单抗在停药后，警惕骨密度下降及锥体骨折等风险，建议 在医师指导下停药，可在停药后转换为双膦酸盐等继续治疗。     

Association between periodontitis and medication-related osteonecrosis of the jaw: A systematic review and meta-analysis

Consensus has yet to be reached about the prevention and treatment of medication-related osteonecrosis of the jaw (MRONJ), which is a treatment sequela of several antiresorptive therapies and other pharmaceutical interventions. Several epidemiologic studies have identified periodontal disease (PD) as a risk factor for this outcome. Thus, the objective of this systematic review and meta-analysis was to investigate this association and its magnitude. A systematic search in MEDLINE via PubMed, Scopus and ISI Web of Science, and a meta-analysis were undertaken. Observational studies that gathered information regarding prefixed definitions for both outcomes were selected, and the relevant information was then extracted, and their risk of bias was evaluated using the Newcastle-Ottawa Scale. The protocol of the study was registered on PROSPERO (CRD42019125646). The initial search yielded 757 eligible records, of which 12 were deemed adequate for inclusion (5 cohort studies and 7 case-control studies). On a random-effects meta-analysis, the risk of PD in MRONJ-affected sites compared with at-risk non-affected patients was significantly greater, with a risk ratio of 2.75 (95% CI: 1.67-4.52). Nonetheless, from a pooled analysis of three standardized periodontal measures (ie plaque index, clinical attachment loss and probing depth) no significant results were obtained. MRONJ appears to be associated with an increase in prevalence of PD. The direction of this association, and the factors influencing it must be investigated using further prospective data, and likewise, the possibility for using periodontal therapy as a prevention strategy must be looked into. Periodontal screening needs to be made an indispensable requisite for clinicians in order to establish a correct multidisciplinary approach in MRONJ.     

补肾壮骨膏治疗围绝经期骨质疏松症临床观察

目的观察补肾壮骨膏治疗围绝经期骨质疏松症的临床疗效。方法选取2014年3月～2017年3月在我院就诊的围绝经期骨质疏松症患者80例,随机分为观察组与对照组。观察组40例,服用补肾壮骨膏、碳酸钙片;对照组40例,口服克龄蒙、碳酸钙片。观察组及对照组以4周为1个疗程,3个疗程结束后评估两组治疗效果,检测骨骼矿物质密度(BMD)及性激素(雌激素E2、卵泡刺激素FSH)。结果 3个月后随访,观察组总有效率90.0%高于对照组82.5%,差异有统计学意义(P0.05);两组BMD治疗前后比较,差异有统计学意义(P0.01);观察组E2水平明显高于对照组,FSH水平明显低于对照组,差异有统计学意义(P0.05)。结论补肾壮骨膏治疗围绝经期骨质疏松症临床疗效显著,值得临床推广。     

慢性肾衰患者褪黑素水平、氧化应激、炎症水平与骨密度相关性研究

目的研究慢性肾功能衰竭维持性血液透析(MHD)中褪黑素(MT)水平、氧化应激和炎症状态与骨密度(BMD)的关系。方法选择我院收治的94例慢性肾功能衰竭患者,于2016年5月至2019年2月接受MHD治疗3个月以上;按照BMD分为骨质疏松组(观察组,n=49)和非骨质疏松组(对照组,n=45)。通过酶联免疫吸附试验检测患者血清高级氧化蛋白产物(AOPP),MT水平和炎症因子[肿瘤坏死因子-α(TNF-α),白细胞介素-6(IL-6)和IL-1](ELISA)。此外,通过硫代巴比妥酸(TBA)测定法检测血清中的丙二醛(MDA)水平,并检测腰椎BMD,然后进行相关性分析。结果观察组MT水平显着低于对照组,但AOPP和MDA水平显着高于对照组(P<0.05)。观察组炎症因子(TNF-α,IL-6和IL-1)水平明显高于对照组(P<0.05)。此外,观察组腰椎BMD和T值明显低于对照组(P<0.05)。Pearson相关分析显示AOPP、MDA、TNF-α、IL-6和IL-1水平与BMD呈负相关,但MT与BMD呈正相关(P<0.05)。结论MHD患者容易发生骨质疏松症;氧化应激和炎症程度与BMD呈负相关,但MT与BMD呈正相关。     

丹参川芎联合骨瓜或骨肽对糖尿病骨质疏松患者糖代谢和骨代谢的影响

目的:探讨在丹参川芎治疗基础上,结合骨瓜或骨肽应用于糖尿病骨质疏松症对糖代谢、骨代谢作用价值。方法:选取2016年3月至2017年9月湖北省黄石市第二医院受诊的糖尿病骨质疏松症患者253例作为研究对象。将应用丹参川芎结合骨瓜治疗的128例归为骨瓜组,将予以丹参川芎结合骨肽治疗的125例归为骨肽组,分析2组糖化血红蛋白(Hb A1c)、空腹血糖(FBG) N-端中段骨钙素(N-MID-OT)、骨特异性碱性磷酸酶(BAP),骨形态发生蛋白-2(BMP-2),骨钙素(BBGP)。骨密度(BMD),甲状旁腺素(PTH)、碱性磷酸酶(ALP),β-胶原特殊序列(β-CTx),并比较药物安全性。结果:1)骨瓜组糖代谢Hb A1c(7. 41±0. 64)%、钙离子(2. 21±0. 28) mmol/L、FBG(6. 12±0. 59) mmol/L、血磷(1. 42±0. 25)mmol/L在治疗后与骨肽组Hb A1c(7. 79±0. 51)%、钙离子(2. 27±0. 33) mmol/L、FBG(6. 37±0. 83) mmol/L、血磷(1. 35±0. 31) mmol/L差异无统计学意义(P 0. 05); 2)骨肽组N-MID-OT(16. 37±2. 83) ng/m L和骨瓜组差异无统计学意义(P0. 05),BAP(142. 26±10. 66)μg/L、BGP(5. 07±1. 32)μg/L显著低于骨瓜组,BMP-2 (86. 35±6. 24) ng/L显著高于骨瓜组,差异有统计学意义(P 0. 05); 3)骨肽组BMD(0. 57±0. 13) g/cm3显著高于骨瓜组,PTH(32. 26±2. 15) pg/m L、ALP(72. 35±5. 19) U/L显著低于骨瓜组,差异有统计学意义(P 0. 05),β-CTx(0. 39±0. 02) ng/m L和骨瓜组(0. 42±0. 04)ng/m L差异无统计学意义著(P 0. 05); 4)骨瓜组不良反应率(3. 13%)显著低于骨肽组(9. 60%),差异有统计学意义(P 0. 05)。结论:对于糖尿病骨质疏松症的治疗,基于丹参川芎,增加注射用骨肽比较注射用骨瓜提取物,更能促进患者多项骨代谢指标、血清生化指标及BMD的恢复,二者具有相似的调节糖代谢的作用,但骨肽不良反应相对较高,临床上应结合患者实际情况进行药物的选择。     

腰痛宁胶囊联合碳酸钙D3片治疗老年性骨质疏松性骨痛的临床疗效

目的 探讨腰痛宁胶囊联合碳酸钙D₃片在缓解老年性骨质疏松性骨痛方面的临床疗效。方法 收集自2018年9月-2019年12月在陕西中医药大学附属医院骨伤科门诊就诊，符合老年性骨质疏松症诊断标准，疼痛视觉模拟评分法（visual analogue scale，VAS）评分在3~8分患者120例，随机分为对照组（60例）和治疗组（60例）。对照组口服碳酸钙D₃片作为基础治疗，每次0.6 g，1次/d；治疗组在对照组基础上内服腰痛宁胶囊治疗骨质疏松性骨痛，每次4粒，每晚睡前0.5 h黄酒10 mL兑少量温开水送服。降钙素类其他抗骨质疏松药物，医师知情可不改变剂量的情况下继续使用。连续用药2周，入组前及入组后3、7、14 d各随访1次，共4次，时间窗±1 d。治疗结束后根据各访视期VAS评分改变，以疼痛程度改善情况进行疗效评价。测定治疗前、后患者血清中疼痛相关因子。结果 治疗组60例患者总有效率91.7%。对照组60例患者总有效率23.3%，有效率明显低于治疗组，两组差异具有统计学意义（P<0.05）。治疗组治疗后与治疗前比较，从静息痛、触压痛、活动痛三方面观察，VAS评分均有所下降（P<0.05、0.01），疗效肯定；而对照组治疗后与治疗前比较，VAS评分的变化不明显，疗效不佳。经14 d治疗后，对照组患者血清前列腺素E2（PGE₂）、P物质（SP）和5-羟色胺（5-HT）的水平无显著变化，治疗组均显著下降（P<0.01）。结论 腰痛宁胶囊联合碳酸钙D₃片在缓解老年性骨质疏松症骨痛方面起效快，疗效显著。