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Among the methodological questions raised following the Women’s Health Initiative trial was the alleged disparity between the results of randomized, controlled trials (RCTs) and observational studies on hormone replacement therapy. A similar argument could be posed in regard to treatment of postmenopausal osteoporosis by bisphosphonates: are the results of RCTs in line with ‘real world’ populations? Do the selective cohorts in the RCTs represent women in the routine clinical scenario? Wilkes and co-investigators [1] have looked into this issue by mapping all studies published until 2008, and selecting the largest RCTs on the one hand, as well as observational studies which compared high- with low-compliant patients on the other hand. Data were extracted from 20 RCTs (44,878 postmenopausal women, mean age 68 years) and 11 retrospective, observational studies (331,256 postmenopausal women, median age 68 years). The duration of the majority of the studies was 2–3 years. Highly compliant patients were defined as those who took at least 80% of study medications. Only clinical fractures were assessed, ignoring any vertebral morphometric changes. A 23.8% decreased risk for total fractures was recorded in RCTs when active treatment was compared to placebo, whereas a similar figure of a 20.3% reduction was obtained in highly compliant/persistent bisphosphonate users in observational studies of large databases from routine practices.


  • Amos Pines
    Department of Medicine T, Ichilov Hospital, Tel-Aviv, Israel


  1. Wilkes MM, Navickis RJ, Chan WW, Lewiecki EM. Bisphosphonates and osteoporotic fractures: a cross-design synthesis of results among compliant/persistent postmenopausal women in clinical practice versus randomized controlled trials. Osteoporos Int 2009; July 2 (Epub ahead of print).
  2. Bell KJ, Hayen A, Macaskill P, et al. Value of routine monitoring of bone mineral density after starting bisphosphonate treatment: secondary analysis of trial data. BMJ 2009;338:b2266.
  3. Solomon DH, Avorn J, Katz JN, et al. Compliance with osteoporosis medications. Arch Intern Med 2005;165:2414-19.
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