title: Risk of osteonecrosis in patients taking bisphosphonates for prevention of osteoporosis: a systematic review and meta-analysis.
abstract: CONCLUSIONS
  We aimed to systematically review observational studies evaluating use of bisphosphonates (BPs) and risk of osteonecrosis of jaw (ONJ) or other sites among non-cancer patients.
  
  
  BACKGROUND
  PubMed, EMBASE, and Cochrane Library were screened from database inception to Dec 2012.
  
  
  METHODS
  Two reviewers independently identified cohort and case-control studies evaluating the use of oral or intravenous (IV) BPs and the risk of ONJ and extracted the characteristics of the studies and risk estimates. Pooled estimates of odds ratios and 95 % confidence intervals (CI) were derived by random effects meta-analysis. Subgroup analyses were carried according to patients' characteristics and route of BP use.
  
  
  RESULTS
  We identified 12 studies, including 2,652 cases and 1,571,997 controls. Use of BPs was associated with a significantly increased risk of ONJ or ON of other sites [odds ratio (OR) 2.32; 95 % CI 1.38-3.91; I (2) = 91 %]. The summary OR was 2.91 (95 % CI 1.62-5.22; I (2) = 85.9 %) for adjusted studies. Use of BPs were associated with higher risk on ONJ (OR 2.57; 95 % CI 1.37-4.84; I (2) = 92.2 %) than ON of other sites (OR 1.79; 95 % CI 0.71-4.47; I (2) = 83.3 %). Meta-regression analysis did not find design characteristics or outcome definitions to be significant sources of heterogeneity.
  
  
  CONCLUSIONS
  The available evidence suggests that use of BPs in cancer patients is associated with a substantial risk for ONJ. Patients receiving IV BP are at highest risk.
authors.affiliation: Department of Rehabilitation and Physical Medicine, Taipei Veteran General Hospital, Taipei, Taiwan.
authors.forename: S-H
authors.initials: SH
authors.lastname: Lee
authors.forename: S-S
authors.initials: SS
authors.lastname: Chang
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: R-C
authors.initials: RC
authors.lastname: Chan
authors.forename: C-C
authors.initials: CC
authors.lastname: Lee
mesh_terms: D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000209:etiology*; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004164:Diphosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D010024:Osteoporosis / Q000517:prevention & control*; D017594:Publication Bias; D012107:Research Design; D018570:Risk Assessment / Q000379:methods
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates