title: Efficacy and safety of denosumab versus zoledronic acid in patients with bone metastases: a systematic review and meta-analysis.
abstract: BACKGROUND
  Zoledronic acid (ZA) has been used as the standard treatment for patients with solid cancer or myeloma that has metastasized into bone. A new potential therapeutic strategy, denosumab, is being investigated in a variety of tumors. We conducted a systematic review with meta-analysis of randomized clinical trials assessing the efficacy and safety of denosumab in comparison with ZA in patients with bone metastases secondary to malignancy.
  
  
  METHODS
  A systematic literature search of several electronic databases till July 2011 and a review of reference lists of relevant articles was conducted. Summary relative estimates and 95% confidence intervals (CIs) were calculated using a fixed-effects or random-effects model, depending on the heterogeneity of the included studies.
  
  
  RESULTS
  Seven reports from 3 randomized controlled trials involving 5723 patients were identified. The pooled analysis showed that denosumab significantly delayed time to first on-study skeletal-related event [hazard ratio (HR) = 0.83; 95% CI, 0.76-0.90, P < 0.001], time to multiple skeletal-related events (HR = 0.83; 95% CI, 0.76-0.90, P < 0.001), and pain worsening (HR = 0.92; 95% CI, 0.86-0.99, P = 0.026) for patients with bone metastases compared with ZA. Similar results of the 2 groups were obtained with respect to overall survival (HR = 0.98; 95% CI, 0.91-1.06), disease progression (HR = 1.02; 95% CI, 0.96-1.09), and pain improvement. Summary of the adverse effects revealed similar safety profiles for the 2 drugs.
  
  
  CONCLUSIONS
  Denosumab is superior to ZA in preventing complications for patients with bone metastases. However, further studies are still needed to assess longer-term safety and efficacy of denosumab.
authors: Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wu Han, China.
authors: Lei
authors: L
authors: Sun
authors: Shiying
authors: S
authors: Yu
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D000069448:Denosumab; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D009367:Neoplasm Staging; D061214:Patient Safety; D011379:Prognosis; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000069448:Denosumab; D000077211:Zoledronic Acid