Objective To systematically evaluate the effectiveness and safety of zoledronic acid combined with radiotherapy in treating bone metastasis of malignant tumor. Methods Such databases as PubMed, EMbase, The Cochrane Library (Issue 10, 2012), CBM, CNKI, VIP and WanFang Data were searched to collect randomized clinical trials (RCTs) on bone metastasis of malignant tumor from inception to October, 2012. References of included studies were also retrieved. Two reviewers independently screened studies according to exclusion and inclusion criteria, extracted data, and assessed the methodological quality. Then, meta-analysis was performed using RevMan 5.1 software. Results Twenty nine trials were included involving 2 021 patients. The results of meta-analysis showed that, compared with the radiotherapy alone group, zoledronic acid combined with radiotherapy improved the effectiveness rate of pain relieving at the end of treatment (OR=3.08, 95%CI 2.30 to 4.12, Plt;0.000 01), the effectiveness rate of pain relieving two weeks after treatment (OR=3.39, 95%CI 2.52 to 4.56, Plt;0.000 01), the quality of life (OR=2.74, 95%CI 1.66 to 4.52, Plt;0.000 01) and the ability of movement (OR=2.96, 95%CI 2.16 to 4.05, Plt;0.000 01). Zoledronic acid combined with radiotherapy also reduced the incidence of new bone metastasis (OR=0.21, 95%CI 0.10 to 0.45, Plt;0.000 1) and the incidence rate of bone-related events (OR=0.17, 95%CI 0.03 to 0.92, P=0.04). The adverse reactions of zoledronic acid combined with radiotherapy such as fever (OR=11.92, 95%CI 6.31 to 22.48, Plt;0.000 01) and hypocalcaemia (OR=8.82, 95%CI 1.61 to 48.36, P=0.01), significantly increased. Conclusion Compared with radiotherapy alone, zoledronic acid combined with radiotherapy can relieve bone metastatic pain, effectively enhance patients’ ability of movement, improve quality of life, and decrease new bone metastasis and the occurrence of bone-related events.
目的 探讨独活寄生汤联合唑来膦酸治疗绝经后肝肾亏虚型骨质疏松症（PO）的疗效。 方法 选取2009年2月－2012年12月收治的210例绝经后肝肾亏虚型PO患者，且所有患者均愿意接受研究。采用随机对照试验法，将患者分为A、B、C 3组各70例。A组采用独活寄生汤联合唑来膦酸治疗；B组采用唑来膦酸治疗；C组采用独活寄生汤治疗。观察3组患者治疗前后骨密度、骨源性碱性磷酸酶（NBAP）、骨钙素（BGP）、雌二醇（E2）变化，疗效及不良反应。 结果 骨密度、NBAP、BGP、E2各项指标，治疗前3组患者比较差异无统计学意义（P＞0.05）；治疗后A组各项指标明显优于B组、C组（P＜0.05）；B组与C组对比，差异无统计学意义（P＞0.05）；治疗后A组总有效率为97.14%，与B组、C组对比，差异有统计学意义（P＜0.05）。3组均未见严重不良反应。 结论 独活寄生汤联合唑来膦酸治疗绝经后肝肾亏虚型PO疗效显著，可有效提高患者骨密度、BGP、E2含量，降低骨源性碱性磷酸酶含量，缓解骨质疏松，且无严重不良反应发生，值得临床推广。
【摘要】 目的 评价伴骨转移的非小细胞肺癌（non-small cell lung cancer，NSCLC）患者在接受帕米膦酸二钠和唑来膦酸治疗后的有效性和安全性。 方法 2007年6月-2008年12月，74例伴骨转移的NSCLC，患者接受了双膦酸盐治疗，其中50例接受帕米膦酸二钠治疗，24例接受唑来膦酸治疗。帕米膦酸二钠90 mg，静脉滴注3 h，每4周重复1次；唑来膦酸4 mg，静脉滴注15 min，每4周重复1次。对可能影响其骨相关事件发生时间及生存率的各种临床﹑病理、治疗方法等因素进行分析，用Kaplan-Meier曲线及Log rank检验生存率差异，对不良反应的发生率等采用χ2检验。 结果 18个月无骨相关事件生存率和总体生存率在帕米膦酸二钠及唑来膦酸组分别为19.3%、28.9%（P=0.253）和33.4%、38.2%（P=0.745），两组比较，差异均无统计学意义。两组患者不良反应中帕米膦酸二钠组8例（16.0%），唑来膦酸组6例（25.0%），两组比较差异无统计学意义（χ2=0.200，P=0.655）。7例患者用帕米膦酸二钠治疗失败后再用唑来膦酸治疗，其中位无骨相关事件生存时间为2个月（95%CI：0~4.6）。 结论 唑来膦酸和帕米膦酸二钠在缓解延迟骨相关事件发生时间疗效和不良反应发生率相当。用帕米膦酸二钠治疗失败后再用唑来膦酸可延缓骨相关事件发生时间。【Abstract】 Objective To retrospectively evaluate the efficacy and safety of pamidronate disoclium and zoledronic acid in treating non-small-cell lung cancer (NSCLC) patients with bone metastasis. Methods This study included 74 patients who were treated with bisphosphonate between June 2007 and December 2008. Fifty were treated with pamidronate disodium, and 24 with zoledronic acid. Pamidronate disodium was administered intravenously once for 3 hours every 4 weeks at a dose of 90 mg. Zoledronic acid was given intravenously once for 15 minutes every 4 weeks at a dose of 4 mg. Various clinical, pathological factors and treatment methods related to the occurring time of skeletal related events (SRE) and survival rate were analyzed. Kaplan-Meier curve and Log rank were adopted to detect the difference in survival rate between patients treated with different medicine, and we used χ2 test to discover the rate of adverse events of the patients. Results Eighteen-month SRE-free survival and overall survival rate in the pamidronate disodium and zoledronic acid group were 19.3% vs. 28.9% (P=0.253), and 33.4% vs. 38.2% (P=0.745) respectively. There were 8 (8/50) cases of adverse events in the pamidronate disodium group, and 6 (6/24) in the zoledronic acid group (χ2=0.200, P=0.655). The SRE-free survival time for seven patients who were treated with zoledronic acid after pamidronate disodium failed was 2 months (95%CI: 0-4.6). Conclusions Compared with zoledronic acid, pamidronate has equal efficacy in delaying SRE and incidence of adverse effects. Administering zoledronic acid after pamidronate failed can also delay the occurring time of SRE.
ObjectiveTo observe the treatment effects of zoledronic acid on postmenopausal osteoporosis. MethodsSeventy-two postmenopausal osteoporosis patients from July 2007 to December 2010 were randomly divided into observation group and control group, with 36 patients in each. Traditional drug treatment was used in the control group, while traditional drug treatment and zoledronic acid were used for patients in the observation group. The Indicator of bone mineral density (BMD) and ostocalcin were used to comapre the treatment effects between the two groups after one-year treatment. ResultsThere was a significant difference in BMD and osteocalcin in both the observation group and the control group before and after treatment (P<0.05). The treatment effect is superior in the observation group (P<0.05). ConclusionZoledronic acid is an effective treatment for postmenopausal osteoporosis; it can increase BMD and osteocalcin more effectively.
In this study, the rescue effect of receptor activator for nuclear factor-κB ligand (RANKL) on zoledronate acid (ZOL) induced inhibition of osteoclastogenesis and gene expression of NF-κB p50 and c-Jun was investigated. Mice calvarial osteoblasts (OBs) were harvested and co-cultured with RAW264.7 cells and the cells were divided into 4 groups and received treatment with ZOL and RANKL, either single or combined. The formation of multi-nucleated osteoclast (OC) was examined and gene expression of NF-κB p50 and c-Jun was detected. Group B (ZOL) showed least multi-nucleated OC and resorption lacunae among the 4 groups (P<0.05 or P<0.01) and it was followed by group C (ZOL+RANKL). Group D (RANKL) showed highest OC and resorption lacunae while it was similar to Group A (control) (P>0.05). Gene expression of NF-κB p50 and c-Jun was the lowest in group B (P<0.05 or P<0.01) among the four groups and was significantly increased in group C when compared with group B (P<0.05). Group A and D showed highest gene expression and they were similar to each other (P>0.05). This study suggest that RANKL might partly rescue ZOL induced inhibition of osteoclastogenesis, and the effect of RANKL and ZOL on osteoclastogenesis may be mediated by NF-κB p50 and c-Jun.
ObjectiveTo study the influence of estrogen on zoledronic acid in preventing bone metastasis of breast cancer. MethodsTwo hundred and sixteen breast cancer patients who accepted modified radical mastectomy, chemotherapy, and the prophylaxis of zoledronate acid from January 2006 to December 2009 in this hospital were collected, including luminal A 55 cases, luminal B 63 cases, HER-2 positive 50 cases, triple negative 48 cases. Then these patients were categorized into low estrogen group(n=39) and normal estrogen group(n=177) according to the estrogen level. The patients in the low estrogen group accepted drug induced menopause, in the normal estrogen group didn't accept drug induced menopause. All the patients accepted the therapy of zoledronate acid, then with clinical follow-up for 3-5 years until progressive disease(include neoplasm recurrence, bone metastasis, and other neoplasm metastasis etc.). ResultsThe rate of bone metastasis in the low estrogen group was significantly lower than that in the normal estrogen group (χ2=21.91, P < 0.05). For the patients with luminal A, luminal B, HER-2 positive, and triple negative, the rates of bone metastases in the low estrogen group were significantly lower than those in the normal estrogen group[luminal A:5.13%(2/39) versus 12.43%(22/177), χ2=4.54, P < 0.05;luminal B:7.69%(3/39) versus 13.56%(24/177), χ2=6.04, P < 0.05;HER-2 postive:2.56%(1/39) versus 15.25%(27/177), χ2=3.95, P < 0.05;triple negative:2.56% (1/39) versus 18.08%(32/177), P < 0.05]. The rate of bone metastasis among the different subtype of breast cancer in the low estrogen group was not significant difference(χ2=0.55, P > 0.05). ConclusionsFrom the limited preliminary data, the premenopausal women patients with breast cancer who accepted drug induced menopause afer application of zoledronate acid for preverttion of bone metastasis has a obviously efficacy, and the efficacy has no difference among four molecular subtypes of breast cancer.
ObjectiveTo study the preventive effect of zoledronic acid on the bone metastases of breast cancer. MethodsFour hundred and eighteen female patients with infiltrating ductal carcinoma who were underwent surgery in The First Affiliated Hospital of Xinjiang Medical University from Jan. 2006 to Dec. 2009 were collected and divided into 2 group, patients of prevention group accepted the preventive remedy of zoledronic acid(n=216), but patients of control group didn't accept(n=202). Comparison of incidence of bone metastases and recurrence was performed. ResultsThere were 37(17.13%) patients suffered bone metastases in prevention group and 73(36.14%) patients in control group, so the incidence of bone metastases was higher in control group(χ2=19.45, P<0.05). But there were no significant difference on incidence of pulmonary metastasis, liver metastases, other parts of metastases, multiple organ metastases, and recurrence(P>0.05). ConclusionZoledronic acid could significantly reduce the incidence of bone metastases for patients with breast cancer, who underwent chemotherapy of conventional dose after operation, and it can effectively improve the prognosis of patients with breast cancer.
This study is to investigate the inhibitory effect of different concentrations of zoledronic acid on the activity of osteoclasts, to obtain characteristics on inhibitory effect and to find the lowest effective concentration of zoledronic acid. Marrow cells of C57 mice (6 weeks) were cultured in vitro. Osteoclasts were induced by single nuclear cells. According to the concentration of zoledronic acid, we set up the experimental group with five different concentrations, i.e. 1×10–8 mol/L, 1×10–7 mol/L, 1×10–6 mol/L, 1×10–5 mol/L, and 1×10–4 mol/L. The control group did not contain any bisphosphonate. By tartrate resistant acid phosphatase staining, the number of multinuclear cells, cells through the filter and bone resorption lacune were counted. Five days after the cultivation, the number of multinuclear cells in the experimental group decreased with the increase of concentration of zoledronic acid. Inhibition on the formation of osteoclasts in vitro was effective at 1×10–6 mol/L. At the concentration of 1×10–5 mol/L, the effect of inhibition on migration of osteoclast and bone resorption was more obvious. The effect was further enhanced at concentration of 1×10–4 mol/L. However, the concentration and inhibition curves were gradually mild. The inhibitory effect on different concentrations of zoledronic acid on the activity of osteoclasts was different. The inhibition effect was obvious at 1×10–6 mol/L. We should pay attention to administrate appropriate concentration of zoledronic acid in the clinical applications.