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Osteoporos Int. Author manuscript; available in PMC 2010 June 1.
Published in final edited form as: Osteoporos Int. 2009 June ; 20(6): 973–978. doi:10.1007/s00198-008-0772-2.

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RisedronatE and ALendronate Intervention over Three Years (REALITY): Minimal Differences in FractureRisk Reduction
Jeffrey R Curtis, MD, MPH1,2, Andrew O Westfall, MS3, Hong Cheng, PhD1,4, Kenneth G Saag, MD, MSc1,2,4, and Elizabeth Delzell, ScD1,4 1 Center for Education and Research on Therapeutics (CERTs), University of Alabama at Birmingham, Birmingham, AL
2 3 4

Department of Medicine, University of Alabama at Birmingham, Birmingham, AL Department of Biostatistics, University of Alabama atBirmingham, Birmingham, AL Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL

Background—Bisphosphonates differ in their in vitro potency, avidity for bone, and rapidity of onset in clinical trials. To address potential differences between bisphosphonates in comparative effectiveness, we compared new users of alendronate and risedronate to determine ifthere were differences in the risk of clinical fractures at 1 year and beyond. Methods—Using claims data from a U.S. health care organization, we identified new, adherent users of weekly alendronate or risedronate and assessed subsequent fractures. We calculated fracture incidence rate differences and ratios between the two agents. Results—There were no significant differences in fracture ratesbetween alendronate users (n=12,956) and risedronate users (n=6,107) at 1 year. Using all available data, the rate of hip fracture was higher among risedronate users compared to alendronate users (absolute rate difference approximately 5 per 1000 person-years). Risedronate users had a higher relative rate [RR] of hip fracture (RR = 1.77, 95% CI 1.15 – 2.74) and similar rates of clinical vertebral andnonvertebral fractures compared to alendronate users. Conclusions—The absolute rate of clinical fractures among alendronate and risedronate users was similar both at one year and beyond, suggesting comparable effectiveness between agents. Keywords bisphosphonate; alendronate; risedronate; fracture; osteoporosis

In the clinical trials that led to approval by the U.S. Food and DrugAdministration, both alendronate and risedronate reduced the risk for clinical vertebral and non-vertebral fractures including hip fractures (1–5). A head–to-head study of weekly alendronate and risedronate users showed that alendronate users had greater increases in bone mineral density (BMD) and more suppression of bone turnover markers, but there were no significant differences in the risk offracture (6). Indeed, the sample size and length of follow-up requirements of conducting a head-to-head bisphosphonate trial adequately powered to detect differences in the rate of non-vertebral fractures would lead to a very sizable logistic and financial burden for such a study. Despite these challenges, there is great interest in determining if there are potential differences betweenbisphosphonates in their ability to reduce fracture risk.

Curtis et al.

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Two biologic factors that may be relevant in considering differences between bisphosphonates include their ability to bind tightly to hydroxyapetite in bone, and their ability to inhibit the farnesyl pyrophosphonate synthase (FPPS) enzyme (7–9), the putative target for bisphosphonate activity. Compared to the firstapproved oral bisphosphonate alendronate, risedronate has been shown to bind with less avidity but demonstrates greater inhibition of FPPS. Thus, it has been hypothesized that risedronate may be able to act more quickly to reduce fractures compared to alendronate. A recent observational study of 33,830 persons initiating weekly alendronate or risedronate demonstrated that compared to alendronate, the...
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