阿仑膦酸钠对甲状腺功能减患者骨密度及骨生化、代谢影响的临床研究

目的观察阿仑膦酸钠对甲状腺功能减患者骨密度及骨生化、代谢影响的影响。方法初次诊断为未绝经的甲状腺功能减退女性患者64例,按随机数字表法将其分为治疗组32例,对照组32例。对照组给予左旋甲状腺素替代治疗,治疗组在对照组治疗的基础上给予阿仑膦酸钠70 mg/周,为期12个月。测定治疗不同时间段患者,腰椎1-4(L_(1-4))、左侧股骨颈BMD及血Ca~(2+)、血P~(3+)、1,25-(OH)_2D_3、碱性磷酸酶(ALP)、血清Ⅰ型胶原羧基端吡啶并啉交联肽(ICTP)以及血清骨钙蛋白(bone gla-protein,BGP)水平的变化情况。结果治疗前两组患者的骨密度及骨生化、代谢指标比较不具有统计学意义(P0.05);治疗12个月后,治疗组患者的腰椎1-4(L_(1-4))及股骨颈BMD均显著高于治疗前及同时期对照组(P0.05);治疗后12个月后,两组患者的血ALP、ICTP及BGP均有不同程度升高,治疗组的BGP升高程度明显大于对照组;而对照组的ALP及ICTP升高程度明显大于治疗组,比较有统计学意义(P0.05)。治疗前后两组患者血Ca~(2+)、血P~(3+)、1,25-(OH)_2D_3比较无明显差异(P0.05)。结论阿仑膦酸钠可以明显提升甲状腺功能减患者骨密度,改善骨生化和代谢状态。     

载阿仑膦酸钠骨水泥抑制钛磨屑诱导的假体周围骨溶解

目的 比较载阿仑膦酸钠丙烯酸骨水泥与皮下注射阿仑膦酸钠抑制钛磨眉诱导的骨溶解的效果.方法 48只成年雄性新西兰兔随机均分为无钛磨屑且无阿仑膦酸钠组(A组),有钛磨屑注射且无阿仑膦酸钠组(B组),钛磨屑分别注射0.1%、0.5%、1.0%载阿仑膦酸钠丙烯酸骨水泥组(C、I)、E组),钛磨屑注射且皮下手射阿仑膦酸钠组(F组),每组8只.将载阿仑膦酸钠骨水泥植入兔股骨远端.制备磨屑诱导骨溶解动物模型.术后8周对股骨行组织形态学分析、骨密度(bone mineral density,BMD)测定及界面力学测试结果 B组假体周围可见明显的骨溶解,而C、D、E、F组骨溶解明显少于B组.B组假体周围BMD和骨-骨水泥界面抗剪强度分别较A组下降17%和56%;D组假体周围BMD和界面抗剪强度较B组分别增加29%和62%;E组假体周围BMD和界画抗剪强度较B组分别增加37%和29%;F组假体周围BMD和界面抗剪强度较B组分别增加51%和69%;C组、D组、E组分别与F组比较,假体周围BMD和界面抗剪强度的差异均无统计学意义.结论 载阿仑瞵酸钠丙烯酸骨水泥与皮下注射阿仑瞵酸钠均可在一定程度上抑制磨屑诱导的骨吸收,增强界画抗剪强度.     

五加补骨方及阿仑膦酸钠对模拟失重大鼠骨丢失干预比较

目的:比较五加补骨方及阿仑膦酸钠对3周尾吊模拟失重大鼠前后肢骨胳及肌肉丢失的干预作用.方法:自2009年3月至5月,6周龄雄性Wistar大鼠40只,按体重用随机区组法分为:五加补骨方组(HUC)、阿仑膦酸钠组(HUA)、空白组(CON)、模型组(HU),每组10只.动物实验周期为4周,HUC组全程给予五加补骨方(含刺五加、熟地黄、怀牛膝、牡蛎等)水煎剂,按体重10 ml/kg剂量每日灌胃1次,药液浓度0.704 g/ml;HUA组全程给定量阿仑膦酸钠片溶解混悬剂灌胃,按体重10 ml/kg剂量每周灌胃1次,药液浓度0.9 mg/ml;CON组和HU组均以上述方法全程给予蒸馏水.自第2周始,HU、HUC、HUA组均以尾部悬吊模拟失重3周.第4周末处死大鼠,分别测量血清钙、磷含量及碱性磷酸酶活性(ALP),肱骨和股骨骨密度(BMD)、肱骨和胫骨生物力学性能(biomechanical property)以及肱二头肌和腓肠肌重量指数.结果:与CON组比较,HU组血清Ca显著升高(P＜0.05),后肢BMD、力学性能及肌肉指数均显著降低(P＜0.01);与CON组比较,HUA组血清Ca显著升高(P＜0.05).HUC组血清ALP显著高于其他3组(P＜0.01).与HU组比较,HUC组及HUA组股骨BMD均显著升高,胫骨最大载荷、最大桡度及弹性载荷均有升高趋势;与HU组相比,HUC组及HUA组腓肠肌萎缩分别缓解12.5%和50%(P＞0.05),肱骨BMD均无显著变化,而HUA组肱骨最大桡度(P＜0.01)及弹性桡度(P＜0.05)均较HU组有显著降低.结论:中药复方和阿仑膦酸钠均可有效抑制模拟失重造成的后肢骨及肌肉丢失,改善其力学结构.中药复方在缓解上肢力学性能改变方面表现出一定优势.在治疗航天失重骨丢失类疾病上,五加补骨方与阿仑膦酸钠效果相当.     

阿仑膦酸钠联合钙尔奇D与钙尔奇D单药治疗对老年女性糖尿病骨质疏松疗效的观察

目的观察阿仑膦酸钠(ALN)联合钙尔奇D与钙尔奇D单药治疗老年女性糖尿病骨质疏松症的骨密度变化以及ALN的安全性。方法老年女性2型糖尿病(T2DM)骨质疏松患者72例,随机分为:ALN联合钙尔奇D组37例,给予ALN(70mg/w)和钙尔奇D(600mg/d);钙尔奇D组35例(600mg/d)总疗程6个月。采用双能X线骨密度测量仪(DXA)测定治疗前后腰椎及髋部骨密度。结果钙尔奇D组治疗前后腰椎及髋部骨密度各部位均有增加,但仅在L1及L4部位T值治疗前后有统计学差异(P0.05);ALN联合钙尔奇D治疗组,腰椎和髋部骨密度均有增加,尤其在腰椎的L1、L3、L4及L总部位均有统计学意义(P0.05)。ALN主要不良反应为上腹部不适,钙尔奇D则以便秘为主。结论ALN联合钙尔奇D治疗可以明显提高老年女性糖尿病骨质疏松患者的骨密度,并具有良好的耐受性和安全性。     

阿仑膦酸钠局部给药调节骨代谢在口腔医学中的应用

阿仑膦酸钠(ALN)作为经典的含氮双膦酸盐药物,对治疗骨质流失引起的疾病非常有效,主要通过下调破骨细胞活性,抑制骨吸收,发挥成骨作用。成骨细胞促进骨生成与破骨细胞介导骨吸收在体内形成的平衡被破坏,可能是导致颌骨骨吸收性疾病的唯一原因。尽管ALN在颌骨骨吸收性疾病中应用时具有优势,但长期静脉或口服应用ALN会导致相关性颌骨骨坏死、肾功能衰竭、食道损害等副作用。能否通过改变给药途径减少ALN的不良反应,将其安全有效地应用于颌骨骨吸收疾病中,是目前亟待突破的难点。因此,本文将ALN对骨代谢的作用机制进行简单的阐述,并对其在颌骨骨吸收疾病中应用的优劣进行探讨,以期为ALN局部给药治疗颌骨骨吸收性疾病提供理论指导。     

Periodontitis in Rats Induces Systemic Oxidative Stress That Is Controlled by Bone‐Targeted Antiresorptives

Background: Periodontitis is a chronic, polymicrobial inflammatory disease that degrades connective tissue and alveolar bone and results in tooth loss. Oxidative stress has been linked to the onset of periodontal tissue breakdown and systemic inflammation, and the success of antiresorptive treatments will rely on how effectively they can ameliorate periodontal disease–induced oxidative stress during oral infection. Methods: Rats were infected with polybacterial inoculum consisting of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, as an oral lavage every other week for 12 weeks. Daily subcutaneous injections of enoxacin, bis‐enoxacin, alendronate, or doxycycline were administered for 6 weeks after 6 weeks of polybacterial infection in rats. The serum levels of oxidative stress parameters and antioxidant enzymes, including glutathione peroxidase, superoxide dismutase, and catalase, were evaluated in each of the infected, treated, and sham‐infected rats. Results: Rats infected with the periodontal pathogens displayed a five‐fold increase in the oxidative stress index compared with controls as a result of increased levels of serum oxidants and decreases in total antioxidant activity. The overall decrease in antioxidant activity occurred despite increases in three important antioxidant enzymes, suggesting an imbalance between antioxidant macromolecules/small molecules production and antioxidant enzyme levels. Surprisingly, the bone‐targeted antiresorptives bis‐enoxacin and alendronate inhibited increases in oxidative stress caused by periodontitis. Bis‐enoxacin, which has both antiresorptive and antibiotic activities, was more effective than alendronate, which acts only as an antiresorptive. Conclusion: To the best of the authors’ knowledge, this is the first study to demonstrate that the increased oxidative stress induced by periodontal infection in rats can be ameliorated by bone‐targeted antiresorptives.     

Immunolocalization of Smad-4 in developing molar roots of alendronate-treated rats

Introduction

During root formation, Smad-4 plays a key role during the epithelial–mesenchymal interactions and the Hertwig's epithelial root sheath (HERS) apical proliferation. The root formation and eruption of rat molars is impeded by alendronate treatment due to the inhibition of bone resortion by this drug. The present study aimed to examine the structures affected in the developing root and immunodetect the presence of Smad-4 in rats treated with alendronate.

Methods

Newborn Wistar rats were daily injected 2.5 mg/kg alendronate (ALN) during 9, 12 and 30 days. The controls (CON) were injected with saline. The maxillae were fixed and embedded in paraffin or Spurr resin. Paraffin sections were incubated in Smad-4 antibody that was labelled with DAB. The ultrathin sections were examined in a transmission electron microscope.

Results

In ALN, a short portion of root dentine was formed; the epithelial diaphragm (ED) and the dental follicle (DF) were disorganized by the contact of bone trabeculae. The (CON) molar roots developed normally. Smad-4 labelling was detected in the cytoplasm of fibroblasts and cementoblasts adjacent to the cementum in CON; in ALN group, few ED cells presented weak immunolabelling. Ultrastructurally, the ED and DF appeared disrupted due to the presence of thin bone trabeculae between its cells. It resulted in the lack of apical proliferation of HERS and, consequently, arrest of root formation.

Conclusion

The immunodetection of Smad-4 in the DF cells of ALN specimens indicates that the signalling for the differentiation of these cells into cementum-forming fibroblasts and cementoblasts occurs, despite the impairment of root elongation.     

“六步八法”手法联合阿仑膦酸钠治疗膝关节退行性病变

目的探讨"六步八法"手法联合阿仑膦酸钠治疗膝关节退行性病变临床疗效。方法随机将2012-03—2014-03间收治的60例膝关节退行性病变患均分为对照组和观察组,每组30例。对照组行阿仑膦酸钠治疗,观察组则给予"六步八法"手法联合阿仑膦酸钠治疗。对2组临床疗效、治疗前后VAS及JOA评分进行比较。结果观察组治疗总有效率96.67%,明显高于对照组(80.00%)。两组比较,差异有统计学意义。2组治疗后VAS及JOA评分比较差异有统计学意义(P<0.05)。结论 "六步八法"手法联合阿仑膦酸钠治疗膝关节退行性病变安全有效,能明显改善患者膝关节功能,值得临床推广。