2007年至2012年北京积水潭医院门诊抗骨质疏松药物应用与分析

目的了解医院抗骨质疏松药的应用现状及趋势。方法根据抗骨质疏松药的结构及作用机制不同进行分类,采用世界卫生组织推荐的限定日剂量（DDD）频度分析法,对医院2007年至2012年8月抗骨质疏松药的销售金额、用药频度及日均费用等进行回顾性分析。结果该院抗骨质疏松药的销售金额呈逐年上升趋势,降钙素类药物销售金额占总销售金额的40％,碳酸钙D,片（钙尔奇D600片）用药频度最高,鲑鱼降钙素注射液（密盖息注射液）日均费用最高。结论该院抗骨质疏松药使用基本合理,抗骨质疏松药发展潜力巨大,抗骨质疏松药物应用情况调查对于促进药物合理应用及临床监护具有重要意义。     

不同剂量的环磷酰胺对大鼠骨药理作用探讨

目的　观察不同剂量的环磷酰胺对大鼠骨代谢的影响 ,并探讨用环磷酰胺建立大鼠骨质疏松的动物模型。方法　用三种不同剂量的环磷酰胺分别按每天 1 5mg·kg-1,4 5mg·kg-1,13 5mg·kg-1,灌胃给予♂大白鼠 ,连续 15d ,另设生理盐水正常对照组。各组实验结束后用原子吸收分光光度法和羟脯氨酸法测定该模型大鼠肱骨的骨钙及骨羟脯氨酸含量。同时观察对照组和用药组的体重、白细胞数量以及胸腺、肝、脾、肾、肾上腺和睾丸重量 ,并进行比较。结果　 3种不同剂量的环磷酰胺组大鼠与正常对照组比较 ,大鼠的体重、血白细胞数量、重要的免疫器官等的变化与环磷酰胺的剂量有量效关系 ,随着环磷酰胺的剂量增加而药理作用增强 ,免疫抑制作用增大 ,毒性也增加。对骨代谢的影响观察 ,高、中、低 3种剂量的环磷酰胺均可使大鼠骨钙总量减少和骨钙 /骨干重比值明显降低 ,低剂量的环磷酰胺可使骨羟脯氨酸含量增高 ,中剂量的环磷酰胺可使骨羟脯氨酸含量降低 ,而高剂量环磷酰胺对骨羟脯氨酸没有明显影响。结论　环磷酰胺有促进骨钙释放 ,抑制骨钙沉积的作用 ,中剂量的环磷酰胺 (4 5mg·kg-1)可致大鼠胸腺萎缩 ,可造成大鼠骨矿物质和骨基质等比例的减少的骨质疏松模型。     

补肾方剂对去卵巢大鼠骨质疏松的实验研究

目的:观察补肾方剂预防去卵巢大鼠骨质疏松的作用和作用机理。方法:将大鼠切除双侧卵巢,实验分为假术组、去势组和去势加中药组。另选雌性小鼠,切除卵巢,检测阴道角化上皮细胞阳性率。结果:与假术组比较,去势组胫骨骨小梁体积百分比(TBV%)明显下降(P<0.01),股骨头、股骨近端和远端骨密度(BMD)明显下降(P<0.05)。去势加中药组使 TBV%上升,股骨头、股骨颈和远端处 BMD 上升,与去势组比较差异显著(P<0.05,P<0.01)。去势小鼠加中药组阴道角化上皮细胞阳性率与去势组小鼠比较无显著差异(P>0.05)。结论:补肾方剂有延缓去卵巢大鼠骨质疏松作用,这一作用不是类雌激素作用的结果。     

基于STAT3通路探讨补肾活血方抑制骨细胞凋亡

目的探讨补肾活血方通过信号转导与转录激活子3(STAT3)通路抑制骨细胞的凋亡对骨质疏松的治疗作用。方法选取SPF级健康雌性C57BL/6小鼠75只,随机分为正常对照组11只及造模组64只。造模组采用去势法建立骨质疏松症模型,正常对照组仅暴露双侧卵巢而不切除。将造模成功的小鼠随机分为模型组、补肾活血方低、中、高剂量组及阳性对照组,各12只。模型组和正常对照组分别灌胃给予蒸馏水5 mL·kg^-1,1次/d;补肾活血方低、中、高剂量组分别灌胃给予1.79、3.57、7.14 g·mL^-1补肾活血方药液5 mL·kg^-1,1次/d;阳性对照组灌胃给予0.14 mg·mL^-1尼尔雌醇混悬液5 mL·kg^-1,1次/d。各组小鼠均治疗12周。检测比较各组骨形态参数,骨细胞凋亡指数(AI),以及骨组织B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、Janus激酶2(JAK2)、STAT3表达水平。结果与模型组比较,各组小鼠骨体积分数(BV/TV)、骨小梁厚度(Tb.Th)、...     

Assessing the Association between Important Dietary Habits and Osteoporosis: A Genetic Correlation and Two-Sample Mendelian Randomization Study

Objective: Osteoporosis (OP) is the most common bone disease. The genetic and metabolic factors play important roles in OP development. However, the genetic basis of OP is still elusive. The study aimed to explore the relationships between OP and dietary habits. Methods: This study used large-scale genome-wide association study (GWAS) summary statistics from the UK Biobank to explore potential associations between OP and 143 dietary habits. The GWAS summary data of OP included 9434 self-reported OP cases and 444,941 controls, and the GWAS summary data of the dietary habits included 455,146 participants of European ancestry. Linkage disequilibrium score regression (LDSC) was used to detect the genetic correlations between OP and each of the 143 dietary habits, followed by Mendelian randomization (MR) analysis to further assess the causal relationship between OP and candidate dietary habits identified by LDSC. Results: The LDSC analysis identified seven candidate dietary habits that showed genetic associations with OP including cereal type such as biscuit cereal (coefficient = −0.1693, p value = 0.0183), servings of raw vegetables per day (coefficient = 0.0837, p value = 0.0379), and spirits measured per month (coefficient = 0.115, p value = 0.0353). MR analysis found that OP and PC17 (butter) (odds ratio [OR] = 0.974, 95% confidence interval [CI] = (0.973, 0.976), p value = 0.000970), PC35 (decaffeinated coffee) (OR = 0.985, 95% CI = (0.983, 0.987), p value = 0.00126), PC36 (overall processed meat intake) (OR = 1.035, 95% CI = (1.033, 1.037), p value = 0.000976), PC39 (spirits measured per month) (OR = 1.014, 95% CI = (1.011, 1.015), p value = 0.00153), and servings of raw vegetables per day (OR = 0.978, 95% CI = (0.977, 0.979), p value = 0.000563) were clearly causal. Conclusions: Our findings provide new clues for understanding the genetic mechanisms of OP, which focus on the possible role of dietary habits in OP pathogenesis.     

Network pharmacology explores the mechanisms of Eucommia ulmoides cortex against postmenopausal osteoporosis

Postmenopausal osteoporosis (PMOP) has become one of most frequent chronic disease worldwide with aging population. Eucommia ulmoides cortex (EU), a traditional Chinese medicine, has long since been used to treat PMOP. The aim of this study is to explore pharmacological mechanisms of EU against PMOP through using network pharmacology approach.The active ingredients of EU were obtained from Traditional Chinese Medicine System Pharmacology database, and target fishing was performed on these ingredients in UniProt database for identification of their relative targets. Then, we screened the targets of PMOP using GeneCards database and DisGeNET database. The overlapping genes between PMOP and EU were obtained to performed protein–protein interaction, Gene Ontology analysis, Kyoto encyclopedia of genes, and genomes analysis.Twenty-eight active ingredients were identified in EU, and corresponded to 207 targets. Also, 292 targets were closely associated with PMOP, and 50 of them matched with the targets of EU were considered as therapeutically relevant. Gene ontology enrichment analysis suggested that EU exerted anti-PMOP effects via modulating multiple biological processes including cell proliferation, angiogenesis, and inflammatory response. Kyoto encyclopedia of genes and genomes enrichment analysis revealed several pathways, such as PI3K-AKT pathway, mitogen-activated protein kinase pathway, hypoxia-inducible factors-1 pathway, tumor necrosis factor pathway, and interleukin-17 pathway that might be involved in regulating the above biological processes.Through the method of network pharmacology, we systematically investigated the mechanisms of EU against PMOP. The multi-targets and multi-pathways identified here could provide new insights for further determination of more exact mechanisms of EU.     

Vertical split fracture of the vertebral body following oblique lumbar interbody fusion: A case report

Rationale:Oblique lumbar interbody fusion (OLIF) is an effective and safe surgical technique widely used for treating spondylolisthesis; however, its use is controversial because of several associated complications, including endplate injury. We report a rare vertebral body fracture following OLIF in a patient with poor bone quality.Patient concerns:A 72-year-old male patient visited our clinic for 2 years with lower back pain, leg radiating pain, and intermittent neurogenic claudication.Diagnoses:Lumbar magnetic resonance imaging revealed L4-5 stenosis.Intervention:We performed OLIF with percutaneous pedicle screw fixation and L4 subtotal decompressive laminectomy. We resected the anterior longitudinal ligament partially for anterior column release and inserted a huge cage to maximize segmental lordosis. No complications during and after the operation were observed. Further, the radiating pain and back pain improved, and the patient was discharged. Two weeks after the operation, the patient visited the outpatient department complaining of sudden recurred pain, which occurred while going to the bathroom. Radiography and computed tomography revealed a split fracture of the L5 body and an anterior cage displacement. In revision of OLIF, we removed the dislocated cage and filled the bone cement between the anterior longitudinal ligament and empty disc space. Further, we performed posterior lumbar interbody fusion L4-5, and the screw was extended to S1.Outcomes:After the second surgery, back pain and radiating pain in the left leg improved, and he was discharged without complications.Lesson:In this case, owing to insufficient intervertebral space during L4-5 OLIF, a huge cage was used to achieve sufficient segmental lordosis after anterior column release, but a vertebral body coronal fracture occurred. In patients with poor bone quality and less flexibility, a huge cage and over-distraction could cause a vertebral fracture; hence, selecting an appropriate cage or considering a posterior approach is recommended.     

大鼠椎骨生物力学与骨组织形态计量学的灰色关联分析

目的:运用灰色关联分析,探讨大鼠椎骨生物力学与骨组织形态计量学之间的相关关系.方法:10.5月龄未交配的雌性SD大鼠48只,随机分为6组:① 10.5月龄基础对照组(Basal);② 13月龄假手术组(Sham-1);③ 13月龄去卵巢10周组(OVX-1);④ 16月龄假手术组(Sham-2);⑤ 16月龄去卵巢22...     

利塞膦酸治疗绝经后骨质疏松症的随机双盲对照临床研究

目的:探讨利塞膦酸治疗绝经后骨质疏松症的有效性和安全性。方法:采用随机双盲安慰剂对照平行临床比较研究,共入选病例48例。利塞膦酸组给予利塞膦酸钠片5 mg,qd;安慰剂组给予安慰剂1片,qd;每组均同时给予钙维D,咀嚼片1片,qd;疗程均为12 mo。结果:完成病例共46例,每组各23例。用药后腰椎和髋骨总骨密度,利塞膦酸组增加了(0．04±s 0．04)g·cm-2和(0．03±0．05)g·cm-2,与治疗前比较差异非常显著(P<0．01);安慰剂组无明显变化,2组间比较,差异有非常显著意义(P< 0．01)。利塞膦酸组用药后血骨钙素和I型胶原交联C端多肽分别下降(4±7)μg·L-1和(0．6±0．4)nmol·L-1,与治疗前比较差异非常显著(P<0．01)。不良事件2组各发生1例,组间无显著差异(P>0．05)。结论:利塞膦酸是一种疗效和安全性均良好的治疗绝经后骨质疏松症的药物。