Vertebral fracture efficacy during risedronate therapy in patients using proton pump inhibitors
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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.
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.
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).
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.
Risedronate significantly reduced the risk of new vertebral fractures compared with placebo, regardless of PPI concomitant use.
KeywordsOsteoporosis Proton pump inhibitor Risedronate Upper gastrointestinal adverse events Vertebral fracture
The authors received editorial/writing support in the preparation of this manuscript from The Alliance for Better Bone Health (an alliance between Warner Chilcott Company LLC and sanofi-aventis). Betty Thompson, PhD, from Excerpta Medica provided editorial and writing assistance. The authors are fully responsible for all content and editorial decisions and received no other financial support or other form of compensation related to the development of the paper.
Conflicts of interest
C. Roux has received honoraria and research grants from the Alliance for Better Bone Health. J. L. Goldstein has received research and/or educational grant funding, consulting fees, contract payments, and speaker’s honoraria from AstraZeneca, Given, Horizon, Logical Therapeutics, Novartis, Pfizer, POZEN, Takeda, and TAP; he has received consulting fees from Amgen, Astellas, GlaxoSmithKline, Merck, Novartis, PLX, Procter & Gamble, and Wyeth. Grants have been awarded from Amgen, Novartis, and GlaxoSmithKline and contract payments from Amgen and Glaxo SmithKline. X. Zhou and A. Klemes are employees of Procter & Gamble. R. Lindsay has served as a consultant for Amgen, Eli Lilly, Procter & Gamble, NPS, sanofi-aventis, Roche-GlaxoSmithKline, Novartis, and Wyeth.
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