e., misclassification does not depend on cohort), the study results for the measure of nonvertebral sites and for vertebral sites are likely more attenuated by misclassification than results at the hip. In conclusion, for this large

observational study of more than 200,000 bisphosphonate patients, the apparent differences in the baseline incidence of hip fractures among the alendronate, risedronate, and ibandronate cohorts likely reflect differences in the risk profile of patients prescribed each bisphosphonate. Statistical adjustments could not account for these differences and therefore the design of epidemiological studies should be SCH772984 mouse given careful consideration to account for these differences. Relative to the baseline fracture incidence, the longitudinal analyses indicated that alendronate and risedronate decreased nonvertebral and hip fractures over time, whereas ibandronate did not. All three bisphosphonates decreased vertebral fractures. The reductions Tyrosine Kinase Inhibitor Library cell assay observed in fracture incidence over time within each cohort suggest that the effectiveness

of each bisphosphonate in clinical practice has been consistent with their efficacies demonstrated in randomized controlled trials. Acknowledgement Funding by The Alliance for Better Bone Health (Procter & Gamble Pharmaceuticals and sanofi-aventis). Conflicts of interest Dr. Abelson reports receiving consulting fees from sanofi-aventis, Procter & Gamble, Novartis; serving on speaker’s bureaus for Amgen, Procter & Gamble, Roche, Novartis, and sanofi-aventis. Dr. Gold reports receiving consulting or advisory committee fees from Amgen, Eli Lilly, GlaxoSmithKline, Merck, Procter & Gamble, Roche, sanofi-aventis; serving on

Glycogen branching enzyme speaker’s bureaus for Amgen, Eli Lilly, GlaxoSmithKline, Procter & Gamble, Roche, and sanofi-aventis. Dr. Thomas reports receiving consulting or advisory committee fees from Amgen, Daïchi-Sankyo, Ipsen, Lilly, MSD, Novartis, Procter & Gamble, Roche/GlaxoSmithKline, sanofi-aventis, and Servier; grant support from Lilly, MSD, Nicomed, Novartis, Procter & Gamble, sanofi-aventis, and Servier. Dr. Lange is an employee of Procter & Gamble. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. References 1. Avorn J (2007) In defense of pharmacoepidemiology—embracing the yin and yang of drug research. N Engl J Med 357:2219–2221CrossRefPubMed 2. Perreault S, Dragomir A, Blais L et al (2008) Population-based study of the effectiveness of bone-specific drugs in reducing the risk of osteoporotic fracture. Pharmacoepidemiol Drug Saf 17:248–259CrossRefPubMed 3. Langsetmo LA, Morin S, Richards JB et al (2009) Effectiveness of antiresorptives for the prevention of nonvertebral low-trauma fractures in a population-based cohort of women. Osteoporos Int 20:283–290CrossRefPubMed 4.