伊班膦酸钠和辛伐他汀联合治疗老年性骨质疏松症的临床疗效研究

目的观察伊班膦酸钠联合他汀类药物对老年性骨质疏松症患者的临床疗效。方法将110例老年性骨质疏松症患者随机分为两组,每组55例,对照组单独静脉注射伊班膦酸钠,治疗组给予伊班膦酸钠和辛伐他汀,整个疗程共8个月。观察治疗前后左侧尺骨远端、腰2-4、Wards三角部位的骨密度变化,临床疼痛症状改善的疗效和生化指标的变化。结果两组患者治疗后三个观察部位的骨密度较治疗前均有明显上升(P<0.01);治疗组腰2-4、Wards三角区的骨密度上升幅度明显大于对照组(P<0.05)。治疗组疼痛症状改善的总有效率为92.3%,明显高于对照组的81.8%(P<0.05)。两组治疗前后生化指标无明显变化。结论他汀类药物辛伐他汀对伊班膦酸钠治疗老年性骨质疏松症具有协同作用。     

唑来磷酸针与伊班磷酸钠针治疗骨肿瘤的临床对照

目的:探讨唑来磷酸针与伊班磷酸钠针治疗骨肿瘤临床效果,为临床更好治疗骨肿瘤提供依据。方法:选取本院2012年7月－2014年2月我院肿瘤科骨肿瘤患者88例进行研究,按照临床试验数字随机的方法将患者分为A、B两组,其中A组治疗药物为唑来磷酸针(天晴依泰),B组的治疗药物为伊班磷酸钠针(艾本),观察2组治疗后患者疼痛改善情况、不良反应发生情况、治疗费用以及治疗后患者生活质量情况,并对相关数据进行统计学分析。结果:A组治疗后疼痛缓解率为79.55%,显著低于B组的90.91%,差异有统计学意义,P<0.01。A组治疗后的不良反应及患者表现肾毒性明显高于B组,χ²=8.67,P<0.01,差异具有统计学意义。2组费用比较可以看出,唑来磷酸针明显要比伊班磷酸钠针费用高,2组患者的治疗总费用相比,B组更具有经济价值,P<0.01,差异具有统计学意义。A组患者的生活质量(52.27%)较B组(63.64%),P<0.01,差异具有统计学意义。结论:临床上药物治疗骨肿瘤能够很好的改善骨肿瘤患者的生活质量,伊班磷酸钠针治疗骨肿瘤能够明显改善患者的临床骨痛症状,患者治疗费用低,不良反应和毒副作用少,在临床治疗骨肿瘤上具有重要意义,值得在临床上广泛使用。     

伊班膦酸治疗肺癌骨转移痛疗效及安全性分析

目的:对比分析首剂负荷剂量及常规剂量伊班膦酸钠(ibandronate)治疗肺癌转移性骨痛的疗效和安全性。方法:选择2008年1月-2013年1月我院确诊的非小细胞肺癌骨转移患者40例,随机分为A组(首剂负荷剂量组)和B组(首剂常规剂量组)各20例。A组首剂给予负荷剂量,即伊班膦酸钠6mg+0.9%氯化钠100ml静滴15min以上,每天1次,连用3天,以后每4周重复给予1次维持剂量6mg。B组首剂给予常规剂量,即第1天给予伊班膦酸钠6mg+0.9%氯化钠100ml静滴15min以上,第2天及第3天只给予0.9%氯化钠100ml静滴15min以上作为对照,以后剂量及用法同A组。对比分析2组患者的止痛起效时间、止痛维持时间、用药3个周期后的总有效率及不良反应之间的差异。结果:止痛起效时间:A组平均(2.4±1.09)天,B组平均(7.7±1.86)天,差异有统计学意义(P<0.05)。止痛疗效维持时间:A组平均(22.9±8.27)天,B组平均(16.3±3.52)天,差异有统计学意义(P<0.05)。总有效率:A组85%,B组55%,差异有统计学意义(P<0.05)。2组在不良反应发生情况上无统计学差异(P>0.05)。结论:伊班膦酸钠首剂负荷剂量给药止痛起效快,维持时间长,无严重毒副作用,耐受性良好,可明显改善患者转移性骨痛,提高生活质量,是非小细胞肺癌转移性骨痛治疗的一个新选择。     

Double-blind, randomised, placebo-controlled, dose-finding study of oral ibandronate in patients with metastatic bone disease

Background: Bisphosphonates are an important component of the treatment of metastatic bone disease but more potent, oral formulations are required to improve the effectiveness and convenience of treatment. An oral formulation of the new bisphosphonate, ibandronate (BM 21.0955) has recently been developed.Patients and methods: One hundred ten patients with bone metastases (77 breast, 16, prostate, 3 myeloma, 14 others) were recruited from a single institution to this double blind placebo-controlled evaluation of four oral dose levels (5, 10, 20 and 50 mg) of ibandronate. No changes in systemic anti-cancer treatment were allowed in the month before commencing treatment or during the study period. After an initial four-week tolerability phase, patients could continue on treatment for a futher three months without unblinding; patients initially allocated to placebo received ibandronate 50 mg. The primary endpoint was urinary calcium excretion (UCCR). Bone resorption was also assessed by measurement of pyridinoline (Pyr), deoxypyridinoline (Dpd), and the N-terminal (NTX) and C-terminal (Crosslaps) portions of the collagen crosslinking molecules.Results: Two patients did not receive any trial medication thus, 108 patients were evaluable for safety. Ninety-two patients were evaluable for efficacy. A dose dependent reduction was observed in both UCCR and collagen crosslink excretion. At the 50 mg dose level, the percentage reductions from baseline in UCCR, Pyr, Dpd, Crosslaps and NTX were 71%, 28%, 39% 80% and 74% respectively.One or more gastrointestinal (GI) adverse events occurring in the first month of treatment were reported by six (30%), seven (33%), nine (39%), nine (41%) and eleven (50%) patients at the placebo, 5, 10, 20 and 50 mg dose levels respectively. One patient (20 mg dose) developed radiographically confirmed oesophageal ulceration. GI tolerability may have been adversely affected by concommitant administration of non-steroidal anti-inflammatory agents. Nine (8%) patients stopped treatment within the first month due to GI intolerability but these patients were evenly distributed across the five treatment groups. There was no difference in non-GI adverse events between groups.Conclusions: Oral ibandronate has potent effects on the rate of bone resorption at doses which are generally well tolerated. Further development is appropriate to evaluate the effects of long-term administration in the prevention of metastatic bone disease and the management of established skeletal metastases.     

两种静脉使用的双膦酸盐治疗绝经后骨质疏松症的安全性研究

目的评估绝经后骨质疏松症妇女静脉注射唑来膦酸和3个月伊班膦酸钠的安全性。方法分析使用唑来膦酸(n=122)或静脉注射伊班膦酸钠(n=140)治疗的262例绝经后妇女的安全性数据。通过使用标准化问卷在电话访谈中收集安全性数据(包括急性期反应的发生和下颌骨坏死)。结果与伊班膦酸盐治疗的患者相比,唑来膦酸患者的不良事件患者数明显增多,且给药后出现症状类别也较多(P0.05)。除了发烧(在唑来膦酸输注后更常见),其他流感样症状(肌痛、关节痛、头痛)在静脉注射治疗后(24～36 h)出现在相似比例的患者中。大约50%的患者症状持续3 d。输注后症状发生率下降。唑来膦酸治疗后流感样症状发生率高于静脉注射伊班膦酸盐给药后,但之前口服双膦酸盐患者发生率相似。没有发现颌骨坏死、心律失常或骨折愈合延迟。结论尽管静脉注射双膦酸盐通常是安全的,但在临床实践中,静脉注射双膦酸盐后出现的短暂流感样症状似乎比临床试验中报道的更为多见。     

Rapid pain relief and remission of sternocostoclavicular hyperostosis after intravenous ibandronate therapy

Sternocostoclavicular hyperostosis (SCCH) is an infrequent but painful, localized disturbance of bone metabolism of unknown etiology. The diagnosis of SCCH is generally one of exclusion, and it is therefore frequently missed or delayed, leaving patients with pain that frequently fails to respond to standard analgesic therapy. Consequently, SCCH leads to significantly impaired quality of life. Characteristic increased localized bone turnover and inflammatory osteitis provide a strong rationale for using intravenous bisphosphonates to treat the condition. We report on three patients with long-standing, treatment-refractory SCCH in whom intravenous ibandronate injections (a single administration of 4 mg followed by 2 mg every 3 months for up to a year) produced prompt, dramatic, persistent pain relief and resolution of the other symptoms of the disease. We also review recent evidence suggesting that SCCH is more common than generally believed and that technetium-99 bone scanning can aid in making an accurate diagnosis.     

伊班膦酸钠对髋关节置换后假体柄周围骨丢失的预防效果

目的评价全髋关节置换术后伊班膦酸钠的应用对预防股骨假体柄周围骨丢失的临床疗效。方法前瞻性纳入2014年1月—2015年12月汉中市中心医院骨关节创伤科进行全髋关节置换患者100例,采用随机数字表法分为对照组(50例)和试验组(50例),其中试验组患者术后5～7d给予伊班膦酸钠4mg静滴,并于术后每3个月滴注1次。对照组患者不给予,其余治疗方案相同。比较两组患者术前及术后12个月的股骨假体柄周围基于Gruen分区法的7个感兴趣区(region of interest,ROI)的骨密度值改变,以及血钙、磷和碱性磷酸酶水平改变。结果术后12个月,两组股骨假体柄周围骨密度均较术前有所下降,差异有统计学意义(P<0.05),但试验组患者术后12个月的骨密度显著高于对照组,试验组和对照组股骨各测量ROI的骨密度分别为1区(0.94±0.14)g/cm^2vs.(0.81±0.19)g/cm^2,2区(1.54±0.2)g/cm^2vs.(1.34±0.31)g/cm^2,3区(1.71±0.23)g/cm^2vs.(1.39±0.19)g/cm^2,4区(2.04±0.29)g/cm^2vs.(1.74±0.38)g/cm^2,5区(1.81±0.31)g/cm^2vs.(1.62±0.39)g/cm^2,6区(1.62±0.28)g/cm^2vs.(1.40±0.14)g/cm^2,7区(1.21±0.32)g/cm^2vs.(0.94±0.29)g/cm^2,总体均值(1.49±0.32)g/cm^2vs.(1.29±0.41)g/cm^2,差异均有统计学意义(P<0.05)。试验组患者术后12个月的碱性磷酸酶水平显著低于对照组患者[(56.41±8.74)mmol/L vs.(56.41±8.74)mmol/L,P<0.05],但血钙和血磷差异无统计学意义(P>0.05)。试验组中有11例患者在滴注伊班膦酸钠后出现体温升高、头痛、肌肉酸痛等症状,予以对症处理后好转。结论全髋关节置换术后应用伊班膦酸钠能够有效减少股骨假体柄周围骨密度的丢失。     

伊班膦酸钠合成工艺的改进

目的改进伊班膦酸钠的合成工艺。方法以N-甲基正戊胺为原料经加成、水解、成盐、膦酸化、水解、成盐得伊班膦酸钠。结果与结论改进的工艺明显提高了反应收率,工艺条件温和,合成步骤简洁,适合工业化生产。     

Intravenous bisphosphonates for post-menopausal osteoporosis: adherence to a network guideline

What is known and Objective: An evidence‐based guideline on the use of intravenous (i.v.) bisphosphonates in post‐menopausal osteoporosis was developed across a healthcare system and approved by clinical experts and Pharmacy and Therapeutics Committees. The objective of the study was to evaluate adherence to the guideline at hospitals in the healthcare system. Methods: Post‐menopausal women who received i.v. zoledronic acid or i.v. ibandronate for osteoporosis between September 2007 and October 2008 were identified through a data repository that provides patient‐level longitudinal information on diagnoses, medications and laboratory tests. Manual review of electronic medical records supplemented the data capture. The guideline recommends use of i.v. bisphosphonates in patients: (i) who have had a recent vertebral or hip fracture; (ii) who cannot stand or sit upright for 30–60 min; (iii) who have oesophageal dysmotility or varices; (iv) who have documented adherence issues or, (v) who failed to tolerate oral bisphosphonates after 12 months. In addition, specific monitoring tests are recommended prior to administration. Results and Discussion: Among the 220 women that received an i.v. bisphosphonate (hospitals A/B: n = 92 vs. hospital C: n = 128), 72% met the criteria for use. The results were similar when examined by institution (hospitals A/B 66% vs. hospital C 77%; P = 0·094). On review of the electronic medical records, an additional reason for using i.v. bisphosphonates was identified: persistent bone loss despite oral bisphosphonate therapy. When this criterion for use was included, the adherence rate increased to 80% (hospitals A/B 72% vs. hospital C 86%; P = 0·009). Serum calcium and 25‐OH vitamin D were performed in 75% (hospitals A/B 77% vs. hospital C 73%; P = 0·53), and 86% (hospitals A/B 84% vs. hospital C 87%; P = 0·53) of patients respectively. What is new and Conclusion: Adherence to an i.v. bisphosphonates evidence‐based guideline was adequate (defined as at least 80%) although room for improvement in meeting the criteria for use at one hospital and for conducting baseline serum calcium levels was noted. A future project is warranted to re‐assesses adherence after the measures to improve guideline adherence are implemented.     

唑来膦酸和伊班膦酸钠治疗乳腺癌骨转移的疗效和安全性比较

目的评价发生骨转移的乳腺癌患者在接受唑来膦酸和伊班膦酸钠治疗的有效性和安全性。方法47例发生骨转移的乳腺癌分别接受唑来膦酸和伊班膦酸钠治疗。用Kaplan-Meier曲线及Log-rank检验骨相关事件（skeletal related event,SRE）生存时间及总生存率差异,止痛效果及不良反应发生率用x。检验。结果①止痛总有效率唑来膦酸组和伊班膦酸钠组分别为88．9％（24／27）和85％（17／20）（P=0．467）。②1、2、3年无SRE生存率唑来膦酸组分别为88．7％、44．4％、24．2％,伊班膦酸钠组分别为94．7％、40．5％、5．8％（P=0．744）。（觐、3、4年总生存率唑来膦酸组分别为70．4％、40．7％、23．1％,伊班膦酸钠组分别为85％、46．7％、17．5％（P=0．994）。①②③差异均无统计学意义。④1、2、3年无SRE生存率首发表现单纯骨转移组为92％、50．8％、23．8％,首发合并局部复发及其他脏器转移组为85．4％、21．4％、5．3％（P=0．012）。⑤2、3年总生存率首发单纯骨转移组95．8％、74．2％,首发合并局部复发及其他脏器转移组为56．5％、10．1％（P〈0．001）。④⑤差异有统计学意义。不良反应发生2组无明显差别。结论唑来膦酸在延迟乳腺癌骨转移SRE发生及总生存方面不优于伊班膦酸钠,首发合并其他脏器转移患者预后不良,在不良反应发生率及疼痛控制方面2者疗效相当。