唑来膦酸对高龄女性骨质疏松症患者骨密度和血清骨转换标志物的影响

目的了解唑来膦酸对高龄女性骨质疏松症患者骨密度(BMD)和血清骨转换标志物(BTMs)的影响。方法纳入年龄≥80岁的女性骨质疏松症患者30例,予碳酸钙D3咀嚼片1片,嚼服,bid;骨化三醇胶丸0.25μg,po,bid。12个月后予唑来膦酸5 mg静脉滴注1次,并维持原补钙和活性维生素D方案。检测入组时、唑来膦酸治疗前、治疗后12个月患者血清Ⅰ型胶原交联C-末端肽(CTX)、Ⅰ型前胶原N-端前肽(PINP)和骨钙素(OC)的水平,同时测量股骨颈、总髋部和腰椎1-4处的BMD。观察应用唑来膦酸72 h内不良反应发生情况。结果与入组时比较,唑来膦酸治疗前患者血清CTX、PINP和OC水平有所升高,股骨颈、总髋部和腰椎1-4处的BMD有所降低,但大部分指标差异无显著意义(P>0.05)。唑来膦酸治疗后12个月,患者血清CTX、PINP和OC水平均明显低于入组时和唑来膦酸治疗前(P<0.05或P<0.01),而股骨颈、总髋部和腰椎1-4处的BMD则显著高于入组时和唑来膦酸治疗前(P<0.05或P<0.01)。未见严重不良反应发生。结论唑来膦酸能降低高龄女性骨质疏松症患者的血清BTMs水平,并提高BMD。     

唑来膦酸对老年骨质疏松症患者骨密度和疼痛程度及骨代谢的影响

目的 观察唑来膦酸对老年骨质疏松症患者骨密度、疼痛程度及骨代谢的影响。方法 选取2020年8月—2022年8月福建省立医院收治的老年骨质疏松症患者90例,根据随机数字表法分为阿仑膦酸组、唑来膦酸组,各45例。在常规治疗基础上,阿仑膦酸组予以阿仑膦酸持续治疗3个月,唑来膦酸组则予以唑来膦酸。比较2组临床疗效,治疗前、治疗3个月后L_2～4侧位及右股骨颈骨密度、骨代谢指标、视觉模拟评分法(VAS)评分、Oswestry功能障碍指数,并观察2组不良反应。结果 唑来膦酸组总有效率高于阿仑膦酸组(95.56%vs. 80.00%,χ²=5.075,P=0.024)。治疗3个月后,2组L_2～4侧位及右股骨颈骨密度高于治疗前,且唑来膦酸组高于阿仑膦酸组(P<0.05或P<0.01);2组Ⅰ型胶原羧基端肽β特殊序列(β-CTX)、抗酒石酸酸性磷酸酶-5b(TRACP-5b)低于治疗前,骨钙素(OC)、Ⅰ型胶原氨基末端肽(NTX)高于治疗前,且唑来膦酸组降低/升高幅度大于阿仑膦酸组(P<0.05或P<0.01);2组...     

骨转换标志物在老年女性骨质疏松症患者静脉滴注唑来膦酸后骨密度变化预测中的价值

目的了解血清骨转换标志物(BTMs)在预测老年女性骨质疏松症(OP)患者静脉滴注唑来膦酸后骨密度(BMD)变化中的价值。方法予100例老年女性OP患者静脉滴注唑来膦酸5 mg,在治疗前、治疗12月末分别检测血清Ⅰ型胶原C-末端肽交联(CTX)、Ⅰ型原胶原N-端前肽(P1NP)水平和股骨颈骨密度(FNBMD)、总髋部骨密度(THBMD)和腰椎1-4骨密度(LSBMD)值。比较治疗前后血清BTMs和BMD的差异,并分析治疗前血清BTMs水平和BMD变化值(△BMD)的相关性。结果与治疗前比较,治疗12月末患者血清CTX和P1NP均显著下降(P <0.01), FNBMD、 THBMD和LSBMD均显著增加(P <0.01)。治疗前血清CTX水平与△FNBMD (r=0.248, P <0.05)、△THBMD (r=0.345,P <0.01)呈正相关,血清P1NP水平与△FNBMD (r=0.302, P <0.01)、△THBMD (r=0.266, P <0.05)呈正相关,而血清CTX和P1NP与△LSBMD均无明显相关(P> 0.05)。结论血清BTMs对老年女性OP患者静脉滴注唑来膦酸后BMD增高有一定的预测价值,其中血清CTX、 P1NP越高,患者股骨颈和总髋部BMD上升越明显。     

利塞膦酸钠联合阿法骨化醇治疗绝经后骨质疏松32例

目的观察利塞膦酸钠联合阿法骨化醇和钙剂治疗绝经后骨质疏松的疗效。方法收集医院2010年1月至12月绝经后骨量减少和骨质疏松门诊和住院患者64例,随机均分成两组,A组予利塞膦酸钠联合阿法骨化醇、钙尔奇D治疗,B组予钙尔奇D治疗,治疗前后检测腰椎骨密度(BMD)、股骨颈BMD、全髋部BMD、血清Ⅰ型前胶原氨基端前肽(P1NP)、血Ⅰ型胶原交联羧基末端肽β降解产物(β-CTX)、血常规及尿常规等,并记录两组的不良反应。结果治疗12个月后,A组和B组的总有效率分别为90.62%和56.25%;两组患者的腰椎BMD、股骨颈BMD、全髋部BMD等均明显好转,与治疗前相比具有显著性差异(P<0.05),且A组改善程度优于B组(P<0.05);A组的P1NP和β-CTX明显降低(P<0.05)。结论利塞膦酸钠联合阿法骨化醇、钙尔奇D治疗绝经后骨质疏松具有良好的效果,且毒副作用较小。     

六味地黄丸联合唑来膦酸治疗妇女绝经后骨质疏松的临床研究

目的探讨六味地黄丸联合唑来膦酸治疗妇女绝经后骨质疏松的临床效果。方法选取2015年6月—2017年1月广东医科大学附属医院收治的86例绝经后骨质疏松患者,随机分为对照组和治疗组,每组各43例。对照组静脉滴注唑来膦酸注射液,5 mg/次,1次/年。治疗组在此基础上口服六味地黄丸,8丸/次,3次/d。所有患者均连续治疗12个月。观察两组的临床疗效,比较两组治疗前后视觉模拟(VAS)评分、简明健康状况调查量表(SF-36)评分、腰椎1~4骨质密度(BMD)、全髋关节骨BMD、左侧股骨颈BMD、Ⅰ型原胶原氨基端前肽(PINP)、β-胶原降解产物(β-CTX)、碱性磷酸酶(ALP)、骨钙素(BGP)的变化情况。结果治疗后,对照组和治疗组的总有效率分别为79.07%、95.35%,两组比较差异有统计学意义(P0.05)。治疗后,两组VAS评分、血清PINP、β-CTX、ALP及BGP水平显著降低,SF-36评分、腰椎1~4 BMD值、全髋关节骨BMD值、左侧股骨颈BMD值显著升高,同组治疗前后比较差异有统计学意义(P0.05);治疗后,治疗组VAS评分、血清PINP、β-CTX、ALP及BGP水平低于对照组,SF-36评分、腰椎1~4 BMD值、全髋关节骨BMD值、左侧股骨颈BMD值高于对照组,两组比较差异有统计学意义(P0.05)。结论六味地黄丸联合唑来膦酸治疗妇女绝经后骨质疏松具有较好的临床疗效,可有效缓解患者疼痛症状,增加骨密度,提高生活质量,具有一定的临床推广应用价值。     

唑来膦酸对骨质疏松患者骨痛、骨密度和血清骨代谢标志物的影响

目的 探讨唑来膦酸对骨质疏松症(0P)患者骨痛、骨密度(BMD)和血清骨代谢标志物的影响.方法 将2013年6月-2014年7月收治的OP 84例根据治疗方式分为唑来膦酸组与阿仑膦酸钠组,每组42例.记录并比较2组治疗前后骨痛程度、BMD和血清骨代谢标志物水平变化.结果 唑来膦酸组显效率和总有效率高于阿仑膦酸钠组(P＜0.05);2组腰椎正位(L2-4)与右股骨颈BMD在治疗后6、12个月均高于治疗前,且治疗12个月唑来膦酸组高于阿仑膦酸钠组(P＜0.05).唑来膦酸组特异性碱性磷酸酶、β-胶原片段水平低于阿仑膦酸钠组和治疗前,降钙素高于阿仑膦酸钠组和治疗前(P＜0.05).2组不良反应发生率比较差异无统计学意义(P＞0.05).结论 唑来膦酸可有效减轻OP患者骨痛症状,改善患者血清骨代谢相关指标并提高BMD水平.     

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。     

唑来膦酸预防骨质疏松性椎体压缩性骨折术后椎体再发骨折的疗效分析

目的 探究唑来膦酸对骨质疏松性椎体压缩性骨折(OVCF)行椎体成形术治疗后再发骨折的影响。方法回顾性收集OVCF患者152例,根据术后唑来膦酸输注情况分为唑来膦酸组(68例)和对照组(84例)。记录2组术前和术后3、6、12个月的疼痛视觉模拟评分(VAS)和骨密度(BMD)T值。酶联免疫吸附试验测定血清Ⅰ型前胶原氨基端肽(P1NP)、β-胶联降解产物(β-CTX)等骨代谢指标。术后随访2年,记录椎体再发骨折发生情况。结果 与对照组相比,唑来膦酸组术后3、6和12个月BMD T值升高,疼痛VAS、β-CTX和P1NP下降(P<0.05)。术后2年,唑来膦酸组再发椎体骨折率(5.95%,5/84)低于对照组(16.18%,11/68;χ²=4.171,P<0.05)。结论 唑来膦酸可有效预防PVP治疗后OVCF患者再发椎体骨折。     

唑来膦酸联合鲑降钙素治疗老年性骨质疏松的临床效果

目的观察唑来膦酸联合鲑降钙素治疗老年性骨质疏松的临床效果。方法选取2017年6月-2019年6月江西省全南县人民医院收治的老年性骨质疏松患者186例,按照数字随机表法分为试验组和对照组各83例。试验组应用唑来膦酸联合鲑降钙素治疗,对照组应用碳酸钙D3联合鲑降钙素治疗。比较2组患者临床疗效、治疗前后腰椎骨密度、股骨颈骨密度、骨代谢标记物水平。结果试验组总有效率为96.39%,高于对照组的85.54%(χ²=5.936,P=0.015);治疗后,2组腰椎骨密度和股骨颈骨密度均高于治疗前,且试验组高于对照组(P<0.05);治疗后,2组血βⅠ型胶原羧基端肽、N骨钙素和Ⅰ型胶原氨基端延长肽、血降钙素、骨特异性碱性磷酸酶水平均低于治疗前,且试验组低于对照组(P<0.01)。结论唑来膦酸联合鲑降钙素治疗老年性骨质疏松的临床疗效较好,可提高股骨颈骨密度和腰椎骨密度,值得应用推广。     

唑来膦酸联合特立帕肽治疗绝经后骨质疏松症对骨密度影响的临床观察

目的 观察唑来膦酸联合特立帕肽治疗绝经后骨质疏松症对骨密度(BMD)的影响.方法 60例绝经后骨质疏松症患者随机分成唑来膦酸组、特立帕肽组和特立帕肽+唑来膦酸组,观察各组用药后13、26和52周时腰椎、髋部和股骨颈BMD相对于基线的变化.结果 特立帕肽+唑来膦酸组用药后13和26周的腰椎BMD增长百分比与唑来膦酸组、特立帕肽组相比存在显著差异(P＜0.01).用药后52周,特立帕肽+唑来膦酸组与特立帕肽组腰椎BMD无统计学差异,但显著高于唑来膦酸组(P＜0.01).唑来膦酸组、特立帕肽+唑来膦酸组用药后13、26和52周的髋部和股骨颈BMD增长百分比与特立帕肽组相比,差异有统计学意义(P＜0.05),特立帕肽+唑来膦酸组用药后13周的髋部BMD增长百分比与唑来膦酸组相比,差异有统计学意义(P＜0.05).结论 唑来膦酸和特立帕肽联合治疗对提高绝经后骨质疏松症患者的BMD有益.     

唑来膦酸与阿仑膦酸钠治疗Ⅰ型骨质疏松症的临床对比研究

目的：评价唑来膦酸与阿仑膦酸钠治疗Ⅰ型骨质疏松症的疗效和安全性。方法：选取本院100例Ⅰ型骨质疏松症患者,分成A、B组,A组静脉滴注唑来膦酸注射液5mg,每年1次,共2次;B组口服阿仑膦酸钠70mg,每周1次。2组均补充碳酸钙D3 600mg·d-1,治疗时间均为18个月。测定治疗前、后腰椎及髋部骨密度（BMD）值和血钙（Ca2＋）、碱性磷酸酶（ALP）等生化指标,利用Oswestry功能障碍指数（OOI指数）评价治疗前、后疼痛和功能改善情况等。结果：2组治疗前、后生化指标,除治疗12、18个月后ALP变化差异有统计学意义（P〈0．05）外,其余差异均无统计学意义（P〉0．05）;2组治疗前、后ODI评分差异均有统计学意义（P〈0．05）,且治疗12、18个月后2组间比较差异均有统计学意义（P〈0．05）;2组治疗18个月后腰椎、髋部BMD值都有明显上升,与治疗前比较差异有统计学意义（P〈0．05）,治疗18个月后腰椎BMD值组间比较差异有统计学意义（P〈0．05）,但髋部BMD值组间比较差异无统计学意义（P〉0．05）。结论：唑来膦酸与阿仑膦酸钠均能使Ⅰ型骨质疏松症患者显著改善功能并减轻疼痛,增加腰椎、髋部BMD值,长期使用均不影响肝、肾功能,且唑来膦酸比阿仑膦酸钠为更理想的选择。     

加减知柏地黄丸对特发性中枢性性早熟患者骨相关指标的影响

目的 探讨特发性中枢性性早熟女童骨相关指标异常的规律及加减知柏地黄丸治疗的效果.方法 对不同年龄水平的性早熟女童进行N-MID骨钙素片段(N-MID OCT)、Ⅲ型前胶原氨基末端前肽(PⅢNP)和胃促生长素(Ghrelin)含量的测定,将各项指标与正常同龄儿作比较,以探讨患儿骨骼发育异常的规律.其中60例患儿随机单盲分成两组,分配无差异,经加减知柏地黄丸治疗和亮丙瑞林西药对照组治疗,病情缓解后观察骨相关指标.结果 治疗组与对照组治疗前后比较差异无统计学意义(P＞0.05),治疗组治疗前N-MID OCT、PⅢNP、Ghrelin分别为(110.51±11.16)、(31.73±0.30)、(2.73±0.04),治疗6个月,N-MID OCT、PⅢNP分别为(92.22±3.80)和(29.46±0.88),都出现下降,差异均有统计学意义(均P＜ 0.01),Ghrelin为(2.74±0.03),差异无统计学意义(P＞0.05),治疗1年,N-MID OCT、PⅢNP分别为(61.49±4.64)和(23.14±1.47),均下降Ghrelin为(2.86±0.03)上升,差异均有统计学意义(均P＜ 0.01).结论 加减知柏地黄丸可改变ICPP患儿骨相关指标N-MIDOCT、PⅢNP、Ghrelin的水平,抑制成骨细胞过度亢进活动.     

固力康联合钙尔奇D在骨质疏松症合并股骨粗隆间骨折治疗中的疗效及其对骨代谢指标的影响

目的 探讨固力康联合钙尔奇D在骨质疏松症合并股骨粗隆间骨折治疗中的临床疗效,及其对骨密度(BMD)、血清骨硬化蛋白(sclerostin)和骨代谢标志物影响.方法 将150例骨质疏松性股骨粗隆间骨折病人,采用随机双盲对照法分为两组,每组75例,两组病人均经股骨近端髓内钉内固定后,对照组病人给予钙尔奇D口服,治疗组采用固力康联合钙尔奇D,连续用药治疗1年.观察两组病人的临床疗效,测定骨密度,并检测血清中抗酒石酸酸性磷酸酶5b(TRAP5b)、β-胶原特殊序列(β-CTX)、总Ⅰ型前胶原氨基端前肽(T-PINP)、N 端中段骨钙素(N-MID)和sclerostin水平.结果 在治疗3个月后治疗组血清TRAP5b、β-CTX、sclerostin水平降低[(2.47±0.42) U·L-1、(188.46±72.35) ng·L-1、(10.16±3.55) ng·L-1],低于对照组[(3.23±0.25) U·L-1、(325.56±83.56) ng·L-1、(12.78±4.26) ng·L-1;t=13.466、10.742、4.092,均P<0.01],血清T-PINP、 N-MID水平升高[(28.57±8.76)、(22.78±7.56) μg·L-1],高于对照组[(23.75±7.46)、(17.66±8.65) μg·L-1;t=3.628、3.860,均P<0.01].治疗1年后治疗组骨痛缓解情况优于对照组(t=19.709,P<0.01). 此外,治疗1年后,治疗组与对照组腰椎、股骨颈、 Ward氏三角区骨密度均升高[(0.818±0.043)、(0.701±0.055)、(0.503±0.045) g·cm-2],优于对照组[(0.703±0.063)、(0.629±0.035)、(0.429±0.041) g·cm-2;t=13.060、9.565、10.527,均P<0.01],且腰椎BMD升高更加显著.结论 固力康联合钙尔奇D治疗骨质疏松性股骨粗隆间骨折病人有良好的效果,能促进骨形成,抑制骨吸收,减缓骨量丢失,提高骨密度,尤其增加腰椎BMD,可短时间内改善骨代谢指标,降低sclerostin水平,促进骨折愈合,并能够改善骨痛.     

丹杞颗粒联合唑来膦酸治疗老年骨质疏松症的临床研究

目的探讨丹杞颗粒联合唑来膦酸治疗骨质疏松症的有效性与安全性。方法选取驻马店市中心医院于2016年7月—2017年7月收治的骨质疏松症患者118例,根据入院顺序分成对照组和治疗组,每组各59例。对照组患者静脉滴注唑来膦酸注射液,100 mL/次,1次/年;治疗组在对照组基础上口服丹杞颗粒,1袋/次,2次/d。两组患者均治疗12个月。观察两组患者临床疗效,同时比较治疗前后两组患者Oswestry功能障碍指数和SF-36评分及骨代谢指标水平和不良反应情况。结果治疗后,对照组和治疗组临床有效率分别为84.75%和96.61%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者Oswestry功能障碍指数显著降低(P0.05),SF-36评分显著升高(P0.05),且治疗组Oswestry功能障碍指数和SF-36评分情况明显优于对照组(P0.05)。治疗后,两组患者血清骨源性碱性磷酸酶、β骨胶原交联和骨钙素N端中分子片断水平均显著降低(P0.05),且治疗组这些骨代谢指标水平明显低于对照组(P0.05)。治疗期间,对照组患者药物不良反应发生率为18.64%,明显高于治疗组的5.08%,两组比较差异具有统计学意义(P0.05)。结论丹杞颗粒联合唑来膦酸治疗骨质疏松症疗效显著,安全性高,具有一定的临床推广应用价值。     

唑来膦酸治疗绝经后骨质疏松早期药物不良反应分析

目的:为了解唑来膦酸注射液治疗绝经后骨质疏松后早期不良反应情况及发生率,分析骨密度、合并骨折、应用钙剂、骨吸收抑制剂与早期不良反应的相关性。方法:对2009年-2010年12月期间行5mg唑来膦酸注射液治疗绝经后骨质疏松58例患者进行随访,记录用药后30 d内不良反应及其发生率,并进行分析。结果:唑来膦酸用药后早期不良反应主要表现为发热、肌肉痛、流感样症状、头痛、关节痛等症状,其发生率分别为48.3%,25.9%,31.0%,41.4%,24.2%。总不良反应率为60.3%。多为一过性,用药后30 d内均完全缓解。经比较发现骨密度差异、是否合并骨折与不良反应发生率无明显统计学差异;治疗前是否应用钙剂在头痛、肌肉痛、关节痛的发生率反面有明显统计学差异(P<0.05)。治疗前是否应用骨吸收抑制剂药物史的患者与治疗后头痛、肌肉痛、关节痛的发生率有明显统计学差异(P<0.05)。结论:5 mg唑来膦酸注射液治疗早期安全性较高,不良反应症状多为一过性,早期不良反应发生率与骨密度、合并骨折无关,可能与钙剂、骨吸收抑制剂有关。用药前后应及时预防治疗,早期观察无严重后遗症。     

The pharmacokinetics and pharmacodynamics of zoledronic acid in cancer patients with varying degrees of renal function

An open-label pharmacokinetic and pharmacodynamic study of zoledronic acid (Zometa) was performed in 19 cancer patients with bone metastases and known, varying levels of renal function. Patients were stratified according to creatinine clearance (CLcr) into different groups of normal (CLcr > 80 mL/min), mildly (CLcr = 50-80 mL/min), or moderately/severely impaired (CLcr = 10-50 mL/min) renal function. Three intravenous infusions of 4 mg zoledronic acid were administered at 1-month intervals between doses. Plasma concentrations and amounts excreted in urine were determined in all subjects, and 4 patients were administered 14C-labeled zoledronic acid to assess excretion and distribution of drug in whole blood. In general, the drug was well tolerated by the patients. Mean area under the plasma concentration versus time curve and mean concentration immediately after cessation of drug infusion were lower, and mean amounts excreted in urine over 24 hours from start of infusion were higher in normal subjects than in those with impaired renal function (36% vs. 28% of excreted dose), although the differences were not significant. Furthermore, with repeated doses, there was no evidence of drug accumulation in plasma or changes in drug exposure in any of the groups, nor was there any evidence of changes in renal function status. Serum levels of markers of bone resorption (serum C-telopeptide and N-telopeptide) were noticeably reduced after each dose of zoledronic acid across all three renal groups. It was concluded that in patients with mildly to moderately reduced renal function, dosage adjustment of zoledronic acid is likely not necessary.     

Effects of calcitriol on bone mineral density in patients treated with esomeprazole

Context: Proton pump inhibitor (PPI) increases the risk of decrease in bone mineral density (BMD). However, whether calcitrol improves this situation is unknown.

Objective: The current study investigates the effects of calcitriol on BMD in patients with esomeprazole therapy.

Materials and methods: Three hundred and eighty-six participants with gastrointestinal ulcerations were enrolled and randomly assigned into controlled and supplemented groups. Participants in the controlled group were prescribed esomeprazole (20?mg/qd), while the supplemented group was prescribed esomeprazole (20?mg/qd) and calcitriol (2.5?μg/qd). BMD, serum levels of calcium, carboxy-terminal collagen crosslinks (CTX), and alkaline-phosphatase (ALP) were assessed.

Results: (1) No significant between-group difference of age, gender, smoking, previous glucocorticoid use and hemoglobin level was found; (2) after 10.6?±?0.8?d of PPI therapy, BMD T score in the controlled group was slightly increased compared with initial (?1.25?±?0.08 versus ?1.28?±?0.06, p?=?0.084), while there was no change in the supplemented group (?1.25?±?0.05 versus ?1.26?±?0.03, p?=?0.308); (3) during study termination, calcium level in the supplemented group was slightly higher than the controlled group (2.05?±?0.03?mmol/L versus 2.01?±?0.05?mmol/L, p?=?0.073), while no significant differences of CTX (366.57?±?43.71?pg/mL versus 373.15?±?50.23?pg/mL, p?=?0.036) and ALP were found among these two groups (50.47?±?9.32?U/L versus 52.23?±?10.45?U/L, p?=?0.075).

Conclusion: Patients with gastrointestinal ulcerations with esomeprazole therapy, calcitriol supplement showed no efficacy on BMD changes.     

Comparative evaluation of safety and efficacy of pamidronate and zoledronic acid in multiple myeloma patients (single center experience)

Osteolytic bone destruction, caused by the aberrant production and activation of osteoclasts, results in significant morbidity for patients with multiple myeloma (MM). Pamidronate [(3-amino-1-hydroxypropylidene)-1,1-bis-phosphonate] inhibits osteoclastic activity and reduces bone resorption. A potency of zoledronic acid (2-[imidazol-1-yl]-1-hydroxyethylidene-1,1-bisphosphonic acid, a new third generation bisphosphonate, as inhibitor of resorption was 850-fold greater than pamidronate, as was shown in preclinical models of bone resorption. Randomized, double-blind study was conducted to compare the efficacy and safety of zoledronic acid and pamidronate for treating myeloma bone disease. Since March 1999 the efficacy and safety of pamidronate and zoledronic acid is evaluated in MM patients all receiving anti-myeloma chemotherapy acc. to VMCP/VBAP alternating regimen. Nine patients with stage III myeloma and osteolytic lesions (3 female, 6 male, median age 57 years, range 52-67, with monoclonal protein: IgG-7, IgA-2) were randomly assigned (1:1:1 ratio) to treatment with either 4 or 8 mg of zoledronic acid via 15-minute intravenous infusion or 90 mg of pamidronate via 2-hour intravenous infusion every 3 to 4 weeks for 12 months. All patients have received 500 mg of calcium supplements and 500 IU of vit.D, orally, once daily, for the duration of administration of study medication. In extension phase of the study (June 2000-April 2002) patients did not received bisphosphonates. In 7 patients 18 cycles of assessed treatment was administered to each of them and one patient received 16 cycles. One patient died after receiving of 12 pamidronate therapy cycles at 11 month of the trial duration (and at 49 month since MM diagnosis and anti-tumour treatment). The patient's death occurred during the progression of plasma cell proliferation due to acute left ventricle cardiac failure. During the 12-month-period of bisphosphonate treatment skeletal related events (SRE) and progression of osteolysis occurred with the same frequency in 3 treatment groups. One patient experienced spinal cord compression and received radiation to bone and 2 patients experienced vertebral fracture. Time from study entry to the first SRE was 304 days in pamidronate and 366 and 392 days in 4 and 8 mg zoledronic acid group, respectively. The skeletal morbidity rate was identical in all treatment groups. Single hypocalcemic events occurred in 2 patients, mild hypertransaminasemia was observed in 3, worsening of renal function parameters in 2 patients (transient in one of them). Muscular pain and fever up to 39 degrees C (transient and self-limiting "flu-like" symptoms) occurred in 6 patients after several or some dozens of hours from study drug administration. Adverse events were similar in nature and frequency with zoledronic acid and pamidronate and were experienced by a similar proportion of patients in each treatment group. Median time of patient's observation duration after completing of administered treatment with zoledronic acid and pamidronate amounts to 20 months. At present actual median survival time of analysed patients since MM diagnosis is 42 months, since the beginning of treatment with pamidronate and zoledronic acid--33 months, and since completing treatment--20 months and is similar in 3 treatment groups. As was shown in our single center study in MM patients the safety and efficacy of pamidronate 90 mg and zoledronic acid 4 mg and 8 mg in monthly i.v. infusion are comparable. Thus the recommended dosage of zoledronic acid is 4 mg administered as a 15 minute i.v. infusion at intervals of 3 to 4 weeks.     

Zoledronic acid: a review of its use in patients with advanced cancer

Zoledronic acid (Zometa), a parenteral bisphosphonate, is an inhibitor of osteoclast-mediated bone resorption and is used in the management of patients with cancer. Zoledronic acid 4 mg is administered as an intravenous infusion over 15 minutes. In the treatment of bone metastases, zoledronic acid is the first and only bisphosphonate to demonstrate efficacy in patients with a broad range of tumour types and in multiple myeloma. In well-designed trials, a single 4 mg dose of zoledronic acid showed good efficacy in the treatment of patients with hypercalcaemia of malignancy. Zoledronic acid 4 mg was superior to pamidronic acid 90 mg, administered as a 2-hour infusion, as assessed by normalised serum calcium concentrations 10 days after administration. In conjunction with antineoplastic therapy, zoledronic acid was an effective long-term (up to 25 months) treatment for skeletal-related events in patients with bone metastases associated with multiple myeloma or solid tumours. In patients with bone metastases secondary to breast cancer or bone lesions from myeloma, zoledronic acid was at least as effective as pamidronic acid, based on assessments of skeletal-related events 25 months after the start of treatment. In addition, compared with pamidronic acid, the overall risk of developing skeletal complications, including hypercalcaemia of malignancy, was significantly reduced in recipients of zoledronic acid. Compared with pamidronic acid, zoledronic acid reduced the risk of patients with breast cancer developing a skeletal-related event by an additional 20%. Zoledronic acid was significantly more effective than placebo on most efficacy measures in patients with bone metastases secondary to other solid tumours (e.g. lung, prostate) and showed sustained efficacy for up to 15 months. Preliminary data indicate that its efficacy in these patients is sustained for up to 24 months. Estimates of the cost effectiveness of zoledronic acid in the treatment of prostate cancer were consistent with those of other bisphosphonates, and cost-effectiveness ratios were within limits considered acceptable economic value. Zoledronic acid was generally well tolerated, with a tolerability profile similar to that of pamidronic acid and placebo. As with other bisphosphonates, deterioration of renal function has occasionally been reported in patients receiving zoledronic acid and monitoring of serum creatinine is recommended during treatment. The efficacy of zoledronic acid is therefore well established in patients with hypercalcaemia of malignancy and, for up to 25 months, in the treatment of complications arising from metastatic bone disease in patients with multiple myeloma or solid tumours. The clinical profile of zoledronic acid compares favourably with that of pamidronic acid in patients with cancer and zoledronic acid has a more convenient administration schedule with the potential for better compliance. Thus, zoledronic acid is an effective bisphosphonate and is positioned to play an important role in the management of advanced cancer patients with bone metastases.     

国产唑来膦酸注射液治疗转移性骨肿瘤

目的：探讨唑来膦酸注射液治疗转移性骨肿瘤的疗效及安全性.方法：19例住院恶性肿瘤骨转移患者,用唑来膦酸注射液4 mg溶于5%葡萄糖或0.9%氯化钠溶液100 mL中静脉滴注,每4周重复应用1次,治疗有效者连续应用直至进展或患者不能耐受,观察其止痛、改善活动能力、降低高血钙的疗效及不良反应.结果：19例患者中止痛有效率为84.2%（16/19）,活动能力及生活质量改善率89.5%（17/19）.降低高血钙的有效率100%（4/4）.主要不良反应为发热5例次（25%）,感冒样症状4例次（20%）.结论：唑来膦酸治疗恶性肿瘤骨转移安全有效.