紫杉醇加唑来膦酸钠治疗多发骨转移癌32例效果分析

目的:探讨唑来膦酸联合紫杉醇治疗恶性肿瘤骨转移的疗效.方法:32例患者予唑来膦酸钠 4 mg/4 w,加入5%葡萄糖溶液1 000 mL中,静脉缓慢滴注半小时;同时给予紫杉醇150 mg/(kg·w),加入5%葡萄糖溶液250 mL中静脉点滴,28 d一个周期.结果:本组Ⅱ级疼痛18例,Ⅲ级疼痛14例,止痛有效率62.5%;治疗后生活质量显著改善10例,改善8例,改善率56.3%.结论:唑来膦酸钠与紫杉醇合用,能明显增强细胞毒药物的疗效,诱导肿瘤细胞凋亡,抑制血管形成,从而降低骨骼事件的发生率,明显改善患者的生活质量.     

Effect of zoledronic acid on markers of bone turnover and mineral density in osteoporotic patients with beta-thalassaemia

Osteoporosis has emerged as an important cause of morbidity in patients with thalassemia major. Studies regarding the efficacy of bisphosphonates in thalassemia-induced osteoporosis have yielded conflicting results. We performed this prospective study to evaluate the efficacy of zoledronic acid in osteoporotic patients with thalassemia major. Patients, 29, were given 1 mg zoledronic acid intravenously every 3 months for a total of four doses. Twenty age- and sex-matched healthy blood donors served as controls. Before each infusion and 3 months after the last infusion, we determined serum levels of osteoprotegerin (OPG), N-terminal cross-linking telopeptide of type I collagen (NTX), osteocalcin (OC) and insulin-like growth factor 1 (IGF-1). Bone mineral density (BMD) of the lumbar spine was measured at baseline and after the treatment’s completion. At baseline, OPG did not differ significantly between patients and controls (p=0.2), NTX were higher in patients although not significantly (p=0.139), whereas, OC levels were significantly higher and IGF-1 levels significantly lower in patients than in controls (p<0.001 and p<0.006, respectively). Zoledronic acid administration resulted in a significant decrease in NTX, OC and IGF-1 (p<0.05, p<0.001 and p<0.05, respectively) and in a significant increase in OPG and BMD (p<0.05 for both comparisons). The change in NTX, osteocalcin and IGF-1 became significant as early as 3 months after the first administration of zoledronic acid, while the change in OPG reached significance only after three infusions. Our study supports the effectiveness of bisphosphonates in the treatment of thalassemia-induced osteoporosis.     

A prospective analysis of CT density measurements of bone metastases after treatment with zoledronic acid

Objective The objective was to prospectively determine CT density changes in bone metastases, before and after intravenous zoledronic acid for a maximum period of 12 months. Patients and methods Twenty-three consecutive patients presented with bone metastases and underwent therapy with zoledronic acid from December 2004. All patients underwent CT of the chest, abdomen, and pelvis. Bone density, measured in Hounsfield units (HU), was determined by segmenting lesions in the same anatomical area of the metastasis sites on the axial images of the sequential series of CT examinations. The effects of zoledronic acid were evaluated by calculating absolute and relative increases in bone density. Results The patients presented with multiple metastases in 65% of the cases. When compared with the baseline, all groups demonstrated a significant increase in bone density, which significantly (p < 0.01) correlated with the number of zoledronic acid administrations. There was increased bone density of at least 100% in 57%, and an increase of at least 50% in 87% of the patients. This increase was significant in both lytic and sclerotic metastases after 3 months of therapy. No significant bone density difference was found in normal-appearing bone. Conclusion Bone density measured by CT increases at metastatic sites after zoledronic acid treatment, regardless of the type of metastasis, in contrast to apparently normal bone.     

Under usage of zoledronic acid in non-small cell lung cancer patients with metastatic bone disease--a short communication

Background and aim

The use of zoledronic acid (ZA) is now recommended for patients with NSCLC and metastatic bone disease (MBD). We thus examined the rates of ZA administration in NSCLC looking specifically at the use of this drug with systemic chemotherapy (ZCt) and comparing overall survival between patients who had ZCt from diagnosis to those who had chemotherapy (Ct) alone.

Method

In this retrospective audit, we analysed the data of 114 consecutive patients with stage IV NSCLC and MBD at presentation. Forty-three of these patients had received zoledronic acid and chemotherapy (ZCt) and 71 had received chemotherapy alone (Ct).

Results

Forty-three (37.7%, 43/114) of NSCLC patients diagnosed with MBD received ZA with their first chemotherapy (ZCt). Patients on ZCt, after adjustment for the planned prognostic factors (sites of disease, histology and PS), had better overall survival (OS), with a median of 34 weeks, compared to those who received chemotherapy alone, who had a median of 19 weeks (p = 0.03), HR = 0.60 (95%CI: 0.38-0.96). After adjusting for prognostic factors (sex, age. single versus doublet chemotherapy), ZCt patients still maintained a trend to better OS (p = 0.06) HR 0.63 (95%CI: 0.39-1.02) 34 versus 21 weeks.

Conclusions

The percentage of patients with MBD treated with ZA at first chemotherapy (37.7%) is low. The addition of ZA increased OS in NSCLC patients with MBD in this audit. More formal policies and dedicated trials on the treatment of MBD in NSCLC patients need to be put in place.     

唑来膦酸对兔成骨细胞分化及骨保护素分泌的影响

目的 探讨不同浓度的唑来膦酸对成骨细胞分化的影响及其对骨保护素(osteoprotegerin,OPG)分泌的促进作用,以期为唑来膦酸的进一步局部应用提供理论依据.方法 利用组织块培养法进行成骨细胞原代及传代培养.原代培养3d后对细胞爬片行碱性磷酸酶(alkaline phosphatase,ALP)染色,原代培养18 d后将细胞爬片用钙结节染色并鉴定;将唑来膦酸加入含传代第3代成骨细胞悬液的培养液中使其终浓度为0(对照组)、10-5、10-6、10-7、10-8及10-9 mol/L(5个实验组),收集细胞上清液进行ALP检测,用放射免疫测定法测定骨钙素的含量;培养3 d后收集细胞,结合蛋白质印迹法测定细胞分泌的OPG.结果 成骨细胞ALP染色阳性,钙结节茜素红染色呈橘红色钙化结节,唑来膦酸浓度为10-6、10-7、10-8及10-9 mol/L的实验组可促进骨钙素含量增加[分别为(2.80±0.51)、(3.20±0.33)、(4.70±0.35)、(3.40±0.36)μg/L]、ALP活性增强[分别为(5.91±0.35)、(7.62±0.33)、(10.00±0.38)、(8.91±0.29)U/L]、OPG表达升高[分别为(526 955.7±64 068.9)、(661 447.9±75 223.4)、(753 083.3±70 300.0)、(655 184.1±63 401.1)],与对照组[骨钙素含量为(2.40±0.35)μg/L、ALP活性为(4.28±0.36)U/L、OPG表达为(64 713.7±28 715.6)]相比差异均有统计学意义(P＜0.01),并在10-8mol/L组达峰值.结论 唑来膦酸可以提高成骨细胞活性,促进OPG分泌.     

唑来膦酸联合骨化三醇对骨质疏松症患者骨代谢及骨密度的影响

〔摘 要〕 目的：探讨采用唑来膦酸联合骨化三醇治疗骨质疏松症患者对其骨代谢指标、骨密度水平及生活质量的影响。 方法：选取 2017 年 7 月至 2019 年 7 月深圳大学第一附属医院收治的 68 例骨质疏松症患者,按治疗方法不同分为观察组 及对照组各 34 例。对照组予以患者骨化三醇及钙剂进行治疗,观察组在对照组基础上予以患者唑来膦酸注射液进行治疗。 比较两组患者治疗前后的骨代谢及骨密度水平、国际骨质疏松生活质量评估表（QUALEFFO–41）评分以及治疗期间用药安 全性。结果：治疗后,观察组患者骨特异性碱性磷酸酶（BLAP）水平高于对照组,Ⅰ型胶原交联 C 端肽（β–CTX）、骨钙 素 N 端中分子片段（N–MID）及抗酒石酸盐酸性磷酸酶异构体 –5b（TRACP–5b）水平低于对照组,差异具有统计学意义 （P ＜ 0.05）;观察组患者的腰椎、股骨颈、髋部骨密度水平较对照组更高,QUALEFFO–41 评分中疼痛程度、社会功能、 心理状态、身体健康状况自我评价、活动性、日常及家务活动等评分均低于对照组,差异均具有统计学意义（P ＜ 0.05）; 两组患者治疗期间均无严重不良反应发生。结论：对骨质疏松症患者采用唑来膦酸联合骨化三醇进行治疗,可改善患者骨 代谢指标与骨密度水平,提高生活质量,疗效好、安全性佳。     

唑来膦酸联合化疗治疗晚期乳腺癌的疗效观察分析

目的探讨唑来膦酸联合化疗治疗晚期乳腺癌的疗效及对患者生活质量的影响。方法将2010年9月至2012年2月收治的晚期乳腺癌患者共60例,随机分为研究组与对照组,每组30例。研究组给予化疗联合唑来膦酸治疗;对照组除骨转移伴有明显疼痛者同时予以阿仑膦酸钠片口服外,均只应用化疗。对两组间的无进展生存期、总生存期、生活质量进行比较。结果在24个月随访周期后,研究组患者的无进展生存期优于对照组,差异有统计学意义(P0.05),但总生存期两组间差异无明显统计学意义(P0.05)。在生活质量方面,治疗后研究组的生活质量情况较对照组有较大的改善,其中,在躯体功能、总健康、疲倦、恶心呕吐、疼痛、气促和食欲丧失方面的表现优于对照组,差异有统计学意义(P0.05)。结论与化疗相比,唑来膦酸联合化疗能够显著延长晚期乳腺癌患者的无疾病进展期,并改善患者的生活质量。唑来膦酸联合化疗是治疗晚期乳腺癌有效且耐受性好的治疗方案。     

唑来膦酸联合化疗治疗晚期非小细胞肺癌骨转移的临床观察

目的：探讨唑来膦酸联合化疗治疗晚期非小细胞肺癌骨转移的临床疗效。方法：本院收治的晚期非小细胞肺癌骨转移患者62例。给予唑来膦酸治疗,1次,3周,3周为一疗程。分析治疗前、后患者的骨转移灶、疼痛缓解情况。结果：经治疗骨转移灶改善的总有效率为61．3％。54例疼痛症状明显的患者经治疗1周后缓解率为75．9％,6周后缓解率为83．3％。治疗1周、6周后的NRS评分、KPS评分与治疗前比较差异均有统计学意义（P〈O．05）。结论：唑来膦酸联合化疗的临床疗效确切,止痛效果好,给药方便,值得临床推广。     

唑来膦酸对去势大鼠骨折后骨痂和骨微结构的影响简

目的 探讨唑来膦酸对去势大鼠骨折后骨痂和骨微结构的影响.方法 将45只SD雌性大鼠分为骨质疏松组（30只）和正常对照组（15只）,骨质疏松组雌性大鼠被切除双侧卵巢制作骨质疏松动物模型,正常对照组大鼠仅给予假手术;骨质疏松模型建模成功后,将骨质疏松组30只大鼠再次随机分为生理盐水组（15只）和唑来膦酸组（15只）;对两组大鼠制作股骨骨折模型,并分别给予生理盐水和唑来膦酸进行干预;在药物干预4周后,比较生理盐水组和唑来膦酸组骨质疏松大鼠股骨骨痂和骨微结构情况.结果 卵巢切除术后8周,正常对照组和骨质疏松组大鼠股骨的骨密度分别为（0.197±0.028）g/cm2和（0.128±0.037）g/cm2,差异有统计学意义（P＜0.05）;在药物干预4周后,两组骨质疏松大鼠股骨均有骨痂形成,而唑来膦酸组大鼠骨痂明显大于生理盐水组,且骨折线较为模糊;与生理盐水组大鼠比较,唑来膦酸组大鼠骨小梁间隙较小,排列也较为整齐致密,更接近正常对照组大鼠.结论 唑来膦酸可促进骨质疏松大鼠骨折后骨痂形成,并提高其骨密度.