title: Risk of osteonecrosis of the jaw in cancer patients receiving denosumab: a meta-analysis of seven randomized controlled trials.
abstract: OBJECTIVE
  The aim of this study is to gain a better understanding of the overall incidence and risk of osteonecrosis of the jaw (ONJ) in cancer patients receiving denosumab.
  
  
  METHODS
  We performed a meta-analysis of relevant randomized controlled trials identified in Pubmed, Embase, and Cochrane databases. Abstracts presented at the conferences were also searched. Overall incidence rates, relative risk (RR), and 95 % confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials.
  
  
  RESULTS
  A total of 8963 patients with a variety of solid tumors from 7 randomized controlled trials (RCTs) were included for the meta-analysis. The overall incidence of ONJ in cancer patients receiving denosumab was 1.7 % [95 % CI: 0.9-3.1 %]. Also, the use of denosumab was associated with significantly increased risk of ONJ in comparison with bisphosphonates (BPs)/placebo treatment (RR 1.61, 95 % CI: 1.05-2.48, P = 0.029). Subgroup analysis based on controlled therapies demonstrated an increased risk of ONJ in denosumab therapy, when compared with BPs (RR 1.48, 95 % CI: 0.96-2.29, P = 0.078) or placebo (RR 16.28, 95 % CI: 1.68-158.05, P = 0.017). Similar results were observed in prostate cancer (RR 3.358, 95 % CI: 1.573-7.166, P = 0.002) while there was a non-significantly increased risk of denosumab-related osteonecrosis of the jaw (DONJ) in non-prostate cancers (RR 1.142, 95 % CI: 0.678-1.921, P = 0.618).
  
  
  CONCLUSIONS
  The use of denosumab is associated with an increased risk of developing ONJ when compared with BP treatment or placebo, although the increased risk was not statistically significant between denosumab and BP treatment. Further studies are still needed to establish guidelines for the prevention and effective treatment of ONJ.
authors.affiliation: Department of Oncology, The Sixth People's Hospital, Shanghai Jiao Tong University, No. 600, Yishan Road, Shanghai, 200233, China.
authors.forename: Wei-Xiang
authors.initials: WX
authors.lastname: Qi
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Tang
authors.forename: Ai-Na
authors.initials: AN
authors.lastname: He
authors.forename: Yang
authors.initials: Y
authors.lastname: Yao
authors.forename: Zan
authors.initials: Z
authors.lastname: Shen
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D000069448:Denosumab; D005260:Female; D006801:Humans; D007571:Jaw Diseases / Q000139:chemically induced*; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D010020:Osteonecrosis / Q000139:chemically induced*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D017594:Publication Bias; D053245:RANK Ligand / Q000037:antagonists & inhibitors*; D016032:Randomized Controlled Trials as Topic; D012306:Risk
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D053245:RANK Ligand; D000069448:Denosumab