title: Zoledronate for metastatic bone disease and pain: a meta-analysis of randomized clinical trials.
abstract: BACKGROUND
  Randomized controlled trials (RCTs) have reported different results when using zoledronate to treat skeletal-related events (SREs) and bone pain in patients with metastatic bone disease (MBD), and few have looked at the risks and benefits of long-term use of the drug. This meta-analysis aimed to investigate the efficacy and safety of zoledronate to treat MBD in the short and long-term.
  
  
  METHODS
  PubMed, EMBASE, and the Cochrane Library were searched to identify RCTs evaluating zoledronate for MBD. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated.
  
  
  RESULTS
  Twelve RCTs involving 4,450 patients were included in the meta-analysis. Zoledronate decreased the risk of developing SREs compared with placebo (RR 0.75, 95% CI 0.69 to 0.81, P < 0.001). Zoledronate consistently reduced the brief pain inventory (BPI) below baseline compared with placebo at 3, 12, and 24 months. In addition, the likelihood of experiencing a bone pain event was significantly lower in the zoledronate group than in the placebo group (RR 0.83, 95% CI 0.76 to 0.89, P < 0.001). While the two groups did not differ significantly in the incidence of nausea(RR = 1.07, 95% CI 0.96 to 1.19, P = 0.250), emesis (RR 0.94, 95% CI 0.81 to 1.09, P = 0.420), or adverse renal events (RR 1.41, 95% CI 0.94 to 2.11, P = 0.09), the zoledronate group showed a significantly higher relative risk of pyrexia (RR 1.43, 95% CI 1.20 to 1.70, P < 0.001), fatigue (RR 1.26, 95% CI 1.10 to 1.43, P < 0.001), and anemia (RR 1.33, 95% CI 1.14 to 1.55, P < 0.001).
  
  
  CONCLUSIONS
  Compared to placebo, zoledronate significantly reduced the incidence of bone pain and SREs in patients with MBD for periods as long as 24 months. In addition, zoledronate is generally well tolerated over this long period.
authors.affiliation: Department of Anesthesiology, Tumor Hospital of Guangxi Medical University, Nanning, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.forename: Rui
authors.initials: R
authors.lastname: Liang
authors.forename: Ling-Hui
authors.initials: LH
authors.lastname: Pan
authors.forename: Bing
authors.initials: B
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Qian
authors.forename: Jian-Hong
authors.initials: JH
authors.lastname: Zhong
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Zheng
authors.forename: Chang-Long
authors.initials: CL
authors.lastname: Li
mesh_terms: D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000150:complications / Q000556:secondary*; D004164:Diphosphonates / Q000627:therapeutic use*; D005598:Fractures, Spontaneous / Q000517:prevention & control*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D059352:Musculoskeletal Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D016032:Randomized Controlled Trials as Topic; D013117:Spinal Cord Compression / Q000517:prevention & control*; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid