title: Statin therapy and risk of fracture: results from the JUPITER randomized clinical trial.
abstract: OBJECTIVE
  Osteoporosis and cardiovascular disease may share common biological pathways, with inflammation playing a role in the development of both. Although observational studies have suggested that statin use is associated with a lower risk of fractures, randomized trial data addressing this issue are scant.
  
  
  OBJECTIVE
  To determine whether statin therapy reduces the risk of fracture and, in a secondary analysis, whether baseline levels of the inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP) are associated with the risk of fracture.
  
  
  METHODS
  The JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial was an international, randomized, double-blind, placebo-controlled study enrolling 17,802 men older than 50 years and women older than 60 years with hs-CRP level of at least 2 mg/L. Participants were screened from 2003 to 2006 and observed prospectively for up to 5 years (median follow-up, 1.9 years).
  
  
  METHODS
  Rosuvastatin calcium, 20 mg daily, or placebo.
  
  
  METHODS
  Incident fracture was a prespecified secondary end point of JUPITER. Fractures were confirmed by radiographs, computed tomography, bone scan, or other methods. Cox proportional hazards models were used to calculate hazard ratios (HRs) and associated 95% confidence intervals for the risk of fracture according to randomized treatment assignment, as well as increasing tertiles of hs-CRP, controlling for potential confounders.
  
  
  RESULTS
  During the study, 431 incident fractures were reported and confirmed. Among participants allocated to rosuvastatin, 221 fractures were confirmed, compared with 210 among those allocated to placebo, such that the incidence of fracture in the rosuvastatin and placebo groups was 1.20 and 1.14 per 100 person-years, respectively (adjusted HR, 1.06 [95% CI, 0.88-1.28]; P = .53). Overall, increasing baseline hs-CRP level was not associated with an increased risk of fractures (adjusted HR for each unit increase in hs-CRP tertile, 1.06 [95% CI, 0.94-1.20]; P for trend, .34).
  
  
  CONCLUSIONS
  Among men and women with elevated hs-CRP level enrolled in a large trial of rosuvastatin therapy for cardiovascular disease, statin therapy did not reduce the risk of fracture. Higher baseline hs-CRP level was not associated with an increased risk of incident fracture.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00239681.
authors.affiliation: Division of Cardiology, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Peña
authors.affiliation: Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Aspberg
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jean
authors.initials: J
authors.lastname: MacFadyen
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Glynn
authors.affiliation: Division of Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Solomon
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts5Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D050723:Fractures, Bone / Q000097:blood / Q000517:prevention & control*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000627:therapeutic use*; D018570:Risk Assessment; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D002097:C-Reactive Protein