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Comparative safety and effectiveness of alendronate versus raloxifene in women with osteoporosis

  • Kim, Yeesuk1
  • Tian, Yuxi2
  • Yang, Jianxiao2
  • Huser, Vojtech3
  • Jin, Peng4
  • Lambert, Christophe G.5
  • Park, Hojun6
  • You, Seng Chan6
  • Park, Rae Woong6
  • Rijnbeek, Peter R.7
  • Van Zandt, Mui8
  • Reich, Christian8
  • Vashisht, Rohit9
  • Wu, Yonghui10
  • Duke, Jon11
  • Hripcsak, George4, 12
  • Madigan, David4
  • Shah, Nigam H.9
  • Ryan, Patrick B.13
  • Schuemie, Martijn J.13
  • And 1 more
  • 1 Hanyang University, Seoul, 04763, Republic of Korea , Seoul (South Korea)
  • 2 University of California, Los Angeles, CA, 90095, USA , Los Angeles (United States)
  • 3 Lister Hill National Center for Biomedical Communications, National Library of Medicine, Bethesda, MD, 20894, USA , Bethesda (United States)
  • 4 Columbia University, New York, NY, 10032, USA , New York (United States)
  • 5 University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA , Albuquerque (United States)
  • 6 Ajou University, Suwon, 16499, Republic of Korea , Suwon (South Korea)
  • 7 Erasmus University Medical Center, Rotterdam, CA, 3000, The Netherlands , Rotterdam (Netherlands)
  • 8 Real World Insights, IQVIA, Cambridge, MA, 02139, USA , Cambridge (United States)
  • 9 Stanford University School of Medicine, Stanford, CA, 94305, USA , Stanford (United States)
  • 10 The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA , Houston (United States)
  • 11 Georgia Tech Research Institute, Atlanta, GA, 30332, USA , Atlanta (United States)
  • 12 NewYork-Presbyterian Hospital, New York, NY, 10032, USA , New York (United States)
  • 13 Epidemiology Analytics, Janssen Research & Development, Titusville, NJ, 08560, USA , Titusville (United States)
Published Article
Scientific Reports
Springer Nature
Publication Date
Jul 06, 2020
DOI: 10.1038/s41598-020-68037-8
Springer Nature


Alendronate and raloxifene are among the most popular anti-osteoporosis medications. However, there is a lack of head-to-head comparative effectiveness studies comparing the two treatments. We conducted a retrospective large-scale multicenter study encompassing over 300 million patients across nine databases encoded in the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). The primary outcome was the incidence of osteoporotic hip fracture, while secondary outcomes were vertebral fracture, atypical femoral fracture (AFF), osteonecrosis of the jaw (ONJ), and esophageal cancer. We used propensity score trimming and stratification based on an expansive propensity score model with all pre-treatment patient characteritistcs. We accounted for unmeasured confounding using negative control outcomes to estimate and adjust for residual systematic bias in each data source. We identified 283,586 alendronate patients and 40,463 raloxifene patients. There were 7.48 hip fracture, 8.18 vertebral fracture, 1.14 AFF, 0.21 esophageal cancer and 0.09 ONJ events per 1,000 person-years in the alendronate cohort and 6.62, 7.36, 0.69, 0.22 and 0.06 events per 1,000 person-years, respectively, in the raloxifene cohort. Alendronate and raloxifene have a similar hip fracture risk (hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.94–1.13), but alendronate users are more likely to have vertebral fractures (HR 1.07, 95% CI 1.01–1.14). Alendronate has higher risk for AFF (HR 1.51, 95% CI 1.23–1.84) but similar risk for esophageal cancer (HR 0.95, 95% CI 0.53–1.70), and ONJ (HR 1.62, 95% CI 0.78–3.34). We demonstrated substantial control of measured confounding by propensity score adjustment, and minimal residual systematic bias through negative control experiments, lending credibility to our effect estimates. Raloxifene is as effective as alendronate and may remain an option in the prevention of osteoporotic fracture.

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