title: Vertebral fracture efficacy during risedronate therapy in patients using proton pump inhibitors.
abstract: Recent evidence suggests that proton pump inhibitor (PPI) use may affect fracture risk, an important issue for patients being concurrently treated for osteoporosis. The results of our post hoc analysis showed that, regardless of PPI concomitant use, risedronate significantly reduced the risk of new vertebral fractures compared with placebo.
  
  
  BACKGROUND
  Recent evidence suggests that PPI use may affect fracture risk, an important issue for patients being concurrently treated for osteoporosis. Moreover, data suggest that concomitant use of PPIs may wane the anti-fracture effect of bisphosphonates. We explored the relationship between concomitant use of PPIs and incident vertebral fractures among patients treated with risedronate or placebo. Bone mineral density (BMD) and upper gastrointestinal (UGI) adverse events (AEs) were also assessed.
  
  
  METHODS
  This study is a post hoc analysis of a subset of patients participating in three prospective, randomized, placebo-controlled clinical trials, with durations of up to 3 years, which evaluated the efficacy of risedronate in reducing fracture risk: Vertebral Efficacy with Risedronate Trial-MultiNational (VERT-MN); Vertebral Efficacy with Risedronate Trial-North America (VERT-NA); and the risedronate Hip Intervention Program (HIP).
  
  
  RESULTS
  Total enrollment included 2,729 risedronate and 2,725 placebo patients. Concomitant acid-suppressing drugs were used by 8.8% of the total population (n = 482). Regardless of PPI concomitant use, risedronate significantly reduced the risk of new vertebral fractures compared with placebo (risk reduction: PPI users 57%, p = 0.009; PPI non-users 38%, p < 0.001). BMD increased with risedronate, independent of PPI use. PPI users were at a 2.5-fold greater risk of experiencing at least one UGI AE compared with non-users.
  
  
  CONCLUSIONS
  Risedronate significantly reduced the risk of new vertebral fractures compared with placebo, regardless of PPI concomitant use.
authors.affiliation: Department of Rheumatology, AP-HP Cochin Hospital, Paris Descartes University, 27 rue Faubourg Saint Jacques, Paris 75014, France. christian.roux@cch.aphp.fr
authors.forename: C
authors.initials: C
authors.lastname: Roux
authors.forename: J L
authors.initials: JL
authors.lastname: Goldstein
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.forename: A
authors.initials: A
authors.lastname: Klemes
authors.forename: R
authors.initials: R
authors.lastname: Lindsay
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D012968:Etidronic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005272:Femur Neck / Q000503:physiopathology; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D058866:Osteoporotic Fractures / Q000517:prevention & control*; D019338:Polypharmacy; D054328:Proton Pump Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D016032:Randomized Controlled Trials as Topic; D000068296:Risedronic Acid; D016103:Spinal Fractures / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D054328:Proton Pump Inhibitors; D000068296:Risedronic Acid; D012968:Etidronic Acid