The comparative effects of dichloromethylene diphosphonate (Cl2MDP) and ethane-1-hydroxy-1,1-diphosphonate (EHDP) on growth and modeling of the rat tibia

Summary Male rats weighing 100 g were assigned to groups and injected daily for 10 days with vehicle (control), 0.4, 2.0, 4.0, 10.0, or 20.0 mg/kg/day of ethane-1-hydroxy-1,1-diphosphonate (EHDP) or dichloromethylene diphosphonate (Cl₂MDP). The proximal tibial metaphysis and epiphysis were assayed for changes in percentage of hard tissue and bone formation parameters. From the data, information about hard tissue resorption was deduced.All doses of Cl₂MDP and doses of 2.0 mg EHDP/kg/day and greater caused significant increases in percentage of hard tissues with Cl₂MDP being more effective than similar doses of EHDP in decreasing bone resorption.Osteoclast population parameters were increased with all doses of both Cl₂MDP and EHDP with Cl₂MDP having a greater effect than similar doses of EHDP. Decreases in the proliferation of the osteoprogenitor pool parallel the decreases in osteoblasts and bone formation parameters. These decreases in osteoprogenitor pool proliferation do not account for the increases with diphosphonates in osteoclast population parameters.     

骨改良药治疗骨转移的研究进展

骨改良药是一类缓解因骨转移引起的疼痛、病理性骨折、脊髓压迫、高钙血症等一系列骨相关事件药物的总称。目前主要有双膦酸盐类药物和地诺单抗。骨改良药应用于证实有骨质破坏的骨转移患者,作为化疗、放疗的辅助用药,可以明显提高疗效,延长患者的生存期。此外,中医中药也可以有效缓解骨转移引起的一系列相关症状,改善预后。临床工作中要选择合理的药物,才能最大限度地降低骨转移患者的痛苦,提高生活质量。     

双侧上颌骨二膦酸盐颌骨坏死1例报道

二膦酸盐类（bisphosphonates,BP）药物作为一种强效骨吸收抑制剂已用于临床30余年,广泛用于控制与骨代谢改变相关的疾病,如：骨质疏松症、恶性肿瘤骨转移、恶性肿瘤引起的高钙血症、多发性骨髓瘤和Paget骨病。自2003年Marx［1］首次报道二膦酸盐类药物可导致颌骨坏死的现象以来,相关病例报道逐渐增多。根据2014年美国口腔颌面外科医师协会（American Association of Oral and Maxillofacial Surgeons,AAOMS）发布的最新临床指南［2］：由于越来越多患者的颌骨坏死与使用包括二膦酸盐类药物在内的抗骨吸收药物及其他抗血管生成药物（如地诺单抗）相关,推荐把二膦酸盐相关性颌骨坏死（bisphosphonate associated osteonecrosis of the jaw,BRONJ）更名为药物相关性颌骨坏死（medication related osteonecrosis of the jaw,MRONJ）。该指南将MRONJ定义为：以往或目前正在应用抗骨吸收或抗血管生成药物;在口内骨暴露或经过口内、外瘘口可以探及骨面,骨不愈合的时间超过8周;颌骨未曾接受过放疗,或无明确的颌骨转移灶。 本文报道1例拔牙术后出现双侧上颌骨二膦酸盐相关性颌骨坏死的病例,通过手术治疗,效果满意。     

二膦酸盐药物治疗乳腺癌骨转移发生颌骨坏死的临床特点

目的：乳腺癌是女性最常见的恶性肿瘤之一,骨转移在该类患者中较为常见。二膦酸盐药物是预防和控制恶性肿瘤骨转移的一线化学治疗药物,长期应用可以发生颌骨坏死。本研究旨在深入了解应用二膦酸盐药物治疗乳腺癌骨转移后患者发生颌骨坏死的临床特点。方法：回顾分析自2011年1月至2015年8月于北京大学口腔医院就诊并明确诊断为二膦酸盐颌骨坏死的患者,筛选出其中的乳腺癌患者,分析其临床症状、影像学特征及治疗情况。结果：共纳入14例乳腺癌患者,平均年龄60.21岁,平均罹患肿瘤时间9.77年,平均出现骨转移时间为5.67年,平均应用二膦酸盐药物的时间为3.29年。患者均无系统应用激素治疗史,无糖尿病史。9例患者曾经拔牙,口腔内颌骨坏死症状的平均时间为8.58个月,发生在下颌骨者10例,上颌骨3例,上、下颌骨1例。10例经手术治疗的患者中,3例治愈,6例好转,而4例经保守治疗的患者中2例临床症状明显加重。结论：乳腺癌患者自开始应用二膦酸盐药物至发生颌骨坏死的用药时间较长,多数患者没有糖尿病及应用激素治疗史。拔牙本身与颌骨坏死的严重程度没有直接关系,下颌骨是最常受累的部位,手术治疗可以在一定程度上缓解乳腺癌患者发生二膦酸盐相关性颌骨坏死的临床症状。     

伊班膦酸钠治疗绝经妇女骨质疏松的Meta分析

BACKGROUND: Alendronate has a marked enhancing effect on bone mineral density. Ibandronate is the newest (the third generation) bisphosphonates. Evidence-based medicine data on the therapeutic effects of both two drugs remain lacking because of different administration routes and time. OBJECTIVE: To compare the therapeutic effects of ibandronate and alendronate on postmenopausal osteoporosis. METHODS: A computer-based online search was conducted in CNKI, PubMed, CECDB, BMA, VIP, CQVIP, CBM, EMbase, ASP, The Cochrane Library, and EMCC databases from August 1999 to August 2015 to screen the relevant randomized controlled trials. Meta-analysis was performed using Stata/SE version 12.0 software by extracting data from the relevant articles. RESULTS AND CONCLUSION: A total of 10 randomized controlled trials involving 725 patients (ibandronate and alendronate for 379 and 346 patients, respectively) were included. The meta-analysis results showed that bone mineral density was significantly increased (P=0.174, I2= 29.4%, WMD=0.03, 95%CI (0.01-0.04)) at 6 months after treatment and incidence rate of fracture was significantly decreased (P=5.810, I2=0%, OR=0.32, 95%CI: (0.10-1.00)) during 1-year treatment with ibandronate compared with alendronate treatment. However, no significant differences were found between two drug treatments in lumbar spine bone mineral density at 1 year after treatment and the incidence rate of fracture during 6-month treatment. Six-month treatment of ibandronate can improve bone mineral density and reduce the incidence rate of fracture of patients with postmenopausal osteoporosis. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

唑来膦酸抗肿瘤作用研究

双膦酸盐的抗骨吸收机制研究比较明确,已成为治疗恶性肿瘤骨转移的标准药物.越来越多的体内外临床前实验表明,包括唑来膦酸在内的双膦酸盐能通过抑制肿瘤细胞的增殖、黏附、侵袭以及血管牛成、调节免疫等发挥其抗肿瘤作用,与放化疗联合有增效作用.     

Bifosfonati e terapia ortodontica: implicazioni cliniche

ObjectivesThe present review aims to discuss the use of bisphosphonates, the complications associated with their use and their impact on orthodontic treatment.Materials and methodsWe performed a systematic search in PubMed covering publications from January 2000 to January 2013. We also analysed the references of the identified articles.Results and ConclusionsBisphosphonates are frequently used drugs, administered either orally or systemically, for the treatment of osteoporosis or as part of a chemotherapy regimen for varying malignancies. Since orthodontic treatment in adults has become more and more accepted, orthodontists should be aware of the risks, benefits and effects of bisphosphonates on the patient's general health, as well as of their possible influence on orthodontic treatment.     

Incadronate在大白鼠佐剂性关节炎中的关节保护作用

目的 研究二膦酸盐对大白鼠佐剂性关节炎的关节炎症、肿胀以及结构破坏的治疗作用。方法 40只雌性Lewis大白鼠随机分为5组，其中4组通过接种乳酪分枝杆菌诱发关节炎。取接种组中3组自接种后15～42d给予incadronate不同剂量每日1次皮下注射。通过观测关节炎表现，并结合放射学和组织学等方法，分析药物的治疗作用。结果 在incadronate的三种治疗剂量中，大剂量组较小剂量组对关节炎症的抑制作用和关节的保护作用更强。组织学显示，经药物治疗，关节软骨及其下面的骨质结构得到保护；破骨细胞数量减少，并呈现出功能不活跃的彤态。结论 Incadronate可抑制大白鼠佐剂性关节炎的关节炎症、肿胀，保护关节软骨及其下面的骨质结构。提示二膦酸盐类药物可作为类风湿关节炎的辅助治疗药物。     

阿仑膦酸钠对骨质疏松大鼠关节软骨的影响

目的评价阿仑膦酸钠对骨质疏松大鼠关节软骨的保护作用。方法选取36只6月龄的SD雌鼠随机分为3组(每组12只):假手术组(SHAM)仅手术,不切除卵巢;去卵巢+生理盐水(OVX+NS)组和OVX+阿仑膦酸钠(ALEN)组切除双侧卵巢,其中OVX+ALEN组给予阿仑膦酸钠液(3mg/ml)每周36mg/kg剂量灌胃,SHAM组和OVX+NS组给予同等剂量0.9%生理盐水灌胃,于灌胃后4、8、12周时取大鼠近端胫骨常规脱钙,苏木素-伊红(HE)染色切片测量软骨厚度,甲苯胺蓝和Ⅱ型胶原免疫组织化学染色,切片用图像分析仪测量平均灰度值。结果4周时各组的软骨厚度相近;8、12周时OVX+NS组与OVX+ALEN组及SHAM组相比软骨厚度变薄(P<0.05);12周时OVX+NS组Ⅱ型胶原免疫组织化学染色灰度值低于OVX+ALEN组和SHAM组(P<0.05)。结论骨质疏松情况下关节软骨的结构、代谢会发生改变,服用阿仑膦酸钠对关节软骨具有保护作用。     

载双磷酸盐骨水泥的静态机械强度和疲劳极限

目的:研究载双磷酸盐骨水泥的疲劳极限和静态机械强度及相关影响因素.方法制备不同载荷的载双磷酸盐纯粉骨水泥试件,根据纯粉载荷及试件的贮存环境进行分组,检测抗压强度、压缩弹性模量、抗张强度、抗弯强度和疲劳极限,威布尔频率函数分析疲劳极限,激光散射法测定双磷酸盐纯粉的粒径.结果:增加纯粉载荷可提高试件的抗压强度极限、抗张强度极限,降低疲劳极限.体液浸泡可降低试件的抗压强度极限、压缩弹性模最、抗张强度极限及疲劳极限.结论:双磷酸盐纯粉的粒径及分布范围较小,载入后丙烯酸骨水泥的静态机械强度高于美国材料实验协会/国际标准化组织标准,但疲劳极限有一定程度下降.与文献报道双磷酸盐的液剂或片剂磨粉相比,纯粉对骨水泥疲劳极限和静念机械强度的影响最小.