The efficacy and safety of zoledronic acid and strontium-89 in treating non–small cell lung cancer: a systematic review and meta-analysis of randomized controlled trials

  • Zhigang HuEmail author
  • Yufeng Tian
  • Wenxin Li
  • Yushu Ruan
  • Fanjun Zeng
Original Article



Zoledronic acid (ZA) and strontium-89 have been widely used to treat lung cancer with bone metastases. The authors perform this meta-analysis to better evaluate the clinical outcome of ZA and strontium-89 for non–small cell lung cancer (NSCLC) patients.


We carried out standard meta-analysis and network meta-analysis based on a comprehensive data retrieval of EMBASE, PubMed, and Cochrane Library databases (up to March 2019). Random and fixed effects models were used where indicated and between-study heterogeneity was assessed. The primary endpoints were overall survival (OS) and skeletal-related events (SREs). The second endpoints were progression-free survival (PFS) and overall response rate (ORR).


Seven randomized clinical trials, including 1426 NSCLC patients with seven studies of zoledronic acid and two studies of strontium-89, met the inclusion criteria. Compared with the control group, ZA is associated with a OS benefit (1-year survival rate: RR = 1.76, 95% CI 1.36–2.27; and 24-month survival rate: RR = 2.38, 95% CI 1.35–4.19) and a reduction of SREs (RR = 0.57, 95% CI 0.40–0.84) for the patients with bone metastases. No statistical differences were found in PFS and ORR. Network meta-analysis for the patients with bone metastases showed that ZA + strontium-89 and ZA harbored significantly clinical benefits than strontium-89 and placebo in terms of 1-year survival rate and SREs. Both head-to-head study and network meta-analysis showed that strontium-89 had no statistical impact on OS and SREs compared with placebo.


Our analysis demonstrates that ZA +strontium-89 can be considered a priority for NSCLC patients with bone metastases, followed by ZA.


Zoledronic acid (ZA) Non small cell lung cancer Bone metastases Strontium-89 



Non–small cell lung cancer


N-Telopeptide of type I collagen


Overall response rate


Progression-free survival


Relative risk


Skeletal-related events


Zoledronic acid


Author contributions

Z.G.H. and W.X.L. conceived the study and participated in the design. Y.S.R and Y.F T. collected the data. F.J.Z. performed statistical analyses. Z.G.H. drafted the manuscript. W.X.L. and Y.S.R helped to draft the manuscript. F.J.Z. revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.

Compliance with ethical standards

Competing interests

The authors declare that they have no conflict of interest.

Supplementary material

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Respiratory Medicine, The First College of Clinical Medicine ScienceThree Gorges UniversityYichangPeople’s Republic of China
  2. 2.Department of Respiratory MedicineYichang Central People’s HospitalYichangChina
  3. 3.Clinical Research CenterThree Gorges UniversityYichangPeople’s Republic of China

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