The Relationship Between Bisphosphonate Adherence and Fracture: Is It the Behavior or the Medication? Results From the Placebo Arm of the Fracture Intervention Trial

Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research (Impact Factor: 6.83). 04/2011; 26(4):683-8. DOI: 10.1002/jbmr.274
Source: PubMed


Medication compliance may be a surrogate for factors that improve health outcomes such as fractures. Little is known about the size of this potential "healthy adherer" effect. We evaluated the hypothesis that compliance with placebo is associated inversely with bone loss and fractures among women participating in the Fracture Intervention Trial (FIT). Compliance with placebo and alendronate was evaluated using daily medication diaries. Women were defined as having high compliance if they took 80% or more of dispensed study medication. Change in bone mineral density (BMD) was assessed using mixed models comparing women with high versus lower compliance with placebo. Cox proportional-hazards models analyzed the association between placebo compliance and various types of fractures. Among 3169 women randomized to placebo, 82% had high compliance. Compared with women with lower placebo compliance, bone loss at the total hip was lower in compliant placebo-treated women (-0.43%/year versus -0.58%/year, p = .04). Among placebo-treated women, there were 46 hip, 110 wrist, 77 clinical vertebral, and 492 total clinical fractures. Compared with women with lower placebo compliance, women with high placebo compliance had a nonsignificant reduced risk for hip fracture [adjusted hazard ratio (HR) = 0.67, 95% confidence interval (CI) 0.30-1.45]. This trend was not observed for other fractures. Medication compliance may be a proxy for factors that confers benefit on reducing hip fracture (but not other types of fractures) independent of the effect of the medication itself. Nonrandomized studies of interventions designed to maintain or improve bone density and/or hip fracture may need to consider medication compliance as a confounder to better estimate true intervention effects.

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Available from: Jeffrey R Curtis
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    • "Patients' adherence to drugs, highly influenced by their tolerance, would substantially affect the benefits of drugs [41–43]. Therefore the potential risk of side effects should be thoroughly considered during a decision making. "
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    • "Several studies have evaluated the association of adherence to some specific factors [2,5,15,18,21,22,24-26]. In Montori [25] and colleagues, using a prevention and treatment osteoporosis guide by patients taking BPs had no impact on adherence after 6 months, but another experimental study [24] evaluating patients taking alendronate or risedronate showed that the group which received counseling treatment had a better adherence. "
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    ABSTRACT: Background Osteoporosis is a disease of bone metabolism in which bisphosphonates (BPS) are the most common medications used in its treatment, whose main objective is to reduce the risk of fractures. The aim of this study was to conduct a systematic review on BPs adherence for treatment of osteoporosis. Methods Systematic review of articles on BPs adherence for treatment of osteoporosis, indexed on MEDLINE (via PubMed) databases, from inception of databases until January 2013. Search terms were “Adherence, Medication” (MeSH term), “Bisphosphonates” (MeSH term), and “Osteoporosis” (MeSH term). Results Of the 78 identified studies, 27 met the eligibility criteria. Identified studies covered a wide range of aspects regarding adherence and associated factors, adherence and fracture, adherence and BPs dosage. The studies are mostly observational, conducted with women over 45 years old, showing low rates of adherence to treatment. Several factors may influence adherence: socio-economic and cultural, participation of physicians when guidance is given to the patient, the use of bone turnover markers, and use of generic drugs. The monthly dosage is associated with greater adherence compared to weekly dosage. Conclusions Considering the methodological differences between the studies, the results converge to show that adherence to treatment of osteoporosis with BPs is still inadequate. Further experimental studies are needed to evaluate the adherence and suggest new treatment options.
    Full-text · Article · May 2013 · International Archives of Medicine
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    • "Several of these studies have found better cardiovascular and mortality outcomes [1-5], and one even found better outcomes for motor vehicle accidents and workplace accidents [11]. Outcomes not found to be associated with adherence include wrist, vertebral, or non vertebral fractures [17,18]. "
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