title: An evaluation of the Fracture Risk Assessment Tool (FRAX®) as an indicator of treatment efficacy: the effects of bazedoxifene and raloxifene on vertebral, nonvertebral, and all clinical fractures as a function of baseline fracture risk assessed by FRAX®.
abstract: CONCLUSIONS
  The relationship between baseline Fracture Risk Assessment Tool (FRAX®) and treatment efficacy was evaluated using data from a pivotal phase 3 study. Relative risk of vertebral, nonvertebral, and all clinical fractures decreased with increasing probability of fracture for bazedoxifene (BZA) versus placebo but remained generally constant for raloxifene (RLX).
  
  
  BACKGROUND
  To determine whether the FRAX® predicts osteoporosis treatment efficacy, we evaluated reductions in fracture incidence associated with BZA and RLX according to baseline fracture risk determined by FRAX® using data from a phase 3 osteoporosis treatment study.
  
  
  METHODS
  Hazard ratios (HRs) for effects of BZA and RLX versus placebo on incidence of vertebral, nonvertebral, and all clinical fractures were calculated using a Cox regression model. Cox regression analyses were performed in subgroups at or above 10-year fracture probability thresholds determined by FRAX®.
  
  
  RESULTS
  HRs for the risk of vertebral, nonvertebral, and all clinical fractures versus placebo decreased with increasing 10-year fracture probability for BZA, while those for RLX remained stable. In all 10-year fracture probability subgroups, all BZA doses significantly reduced vertebral fracture risk versus placebo (HR = 0.22-0.66). BZA at 20, 40, and 20/40 mg significantly reduced risk of nonvertebral fractures (HR = 0.45, 0.44, and 0.45, respectively) and all clinical fractures (HR = 0.38, 0.41, and 0.40, respectively) for ≥20.0 % fracture probability. Vertebral fracture risk reductions for RLX 60 mg versus placebo were significant in subgroups at lower fracture probabilities (≥2.5- ≥ 10.0 %), but not higher (≥12.5 %), and in no subgroups for nonvertebral or all clinical fractures.
  
  
  CONCLUSIONS
  The antifracture efficacy of BZA increased with increasing baseline FRAX® score, but there was no clear relationship between RLX and baseline FRAX®. These findings provide independent confirmation of current literature, suggesting that the relationship between FRAX® and treatment efficacy varies for different agents.
authors.affiliation: Department of Endocrinology and Unit for Osteoporosis and Metabolic Bone Diseases, Ghent University Hospital, Ghent, Belgium, jean.kaufman@ugent.be.
authors.forename: J-M
authors.initials: JM
authors.lastname: Kaufman
authors.forename: S
authors.initials: S
authors.lastname: Palacios
authors.forename: S
authors.initials: S
authors.lastname: Silverman
authors.forename: S
authors.initials: S
authors.lastname: Sutradhar
authors.forename: A
authors.initials: A
authors.lastname: Chines
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000503:physiopathology; D058866:Osteoporotic Fractures / Q000503:physiopathology / Q000517:prevention & control*; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D018570:Risk Assessment / Q000379:methods; D016103:Spinal Fractures / Q000503:physiopathology / Q000517:prevention & control; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D007211:Indoles; D020849:Raloxifene Hydrochloride; C447119:bazedoxifene