title: β-Adrenergic receptor antagonists and fracture risk: a meta-analysis of selectivity, gender, and site-specific effects.
abstract: By meta-analysis, the risk of fracture was 15% lower in patients treated with β-adrenergic blockers compared to controls independent of gender, fracture site, and dose. This might be attributable to β1-selective blockers.
  
  
  BACKGROUND
  The aim of this study is to determine by meta-analysis whether β-adrenergic blockers (BBs) reduce fracture risk and whether the effect, if demonstrable, is dependent upon selectivity, dose, gender, or fracture site.
  
  
  METHODS
  A literature search was performed in electronic databases MEDLINE, EMBASE, and reference sections of relevant articles to identify eligible studies. Adjusted estimates of fracture risk effect size (ES) were pooled across studies using fixed or random-effects (RE) meta-analysis as appropriate. Dose-related effects were evaluated using meta-regression. To explore the relative efficacy of β1-selective blockers in comparison to nonselective BBs, adjusted indirect comparison was performed.
  
  
  RESULTS
  A total of 16 studies (7 cohort and 9 case-control studies), involving 1,644,570 subjects, were identified. The risk of any fracture was found to be significantly reduced in subjects receiving BBs as compared to control subjects (16 studies, RE pooled ES = 0.86, 95% CI 0.78-0.93; I(2) = 87 %). In a sensitivity analysis limited to those studies deemed to be most robust, the BB effect to reduce fracture risk was sustained (four studies, pooled ES = 0.79, 95% CI 0.67-0.94; I(2) = 96%). The risk of a hip fracture was lower in both women and men receiving BBs (women: pooled ES = 0.86, 95% CI 0.80-0.91; I(2) = 1% and men: pooled ES = 0.80, 95% CI 0.71-0.90; I(2) = 0%). Similar risk reductions were found for clinical vertebral and forearm fractures, although statistical significance was not reached. The reduction in risk did not appear to be dose-related (test for a linear trend p value 0.150). Using adjusted indirect comparisons, it was estimated that β1-selective agents were significantly more effective than nonselective BBs in reducing the risk of any fracture (six studies, β1-selective blockers vs. nonselective BBs: RE pooled ES = 0.82, 95% CI = 0.69-0.97).
  
  
  CONCLUSIONS
  The findings suggest that the risk of fracture is approximately 15% lower in patients treated with BBs compared to controls independent of gender, fracture site, and dose. This risk reduction might be associated with the effects of β1-selective blockers.
authors.affiliation: Department of Endocrinology, 424 General Military Hospital, Ring Road, Efkarpia, P.O. Box 55535, Thessaloniki, Greece, touliskos@gmail.com.
authors.forename: K A
authors.initials: KA
authors.lastname: Toulis
authors.forename: K
authors.initials: K
authors.lastname: Hemming
authors.forename: S
authors.initials: S
authors.lastname: Stergianos
authors.forename: K
authors.initials: K
authors.lastname: Nirantharakumar
authors.forename: J P
authors.initials: JP
authors.lastname: Bilezikian
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005543:Forearm Injuries / Q000517:prevention & control; D006620:Hip Fractures / Q000517:prevention & control; D006801:Humans; D008297:Male; D058866:Osteoporotic Fractures / Q000517:prevention & control*; D012307:Risk Factors; D012737:Sex Factors; D016103:Spinal Fractures / Q000517:prevention & control
chemical_list: D000319:Adrenergic beta-Antagonists