Review Article| Volume 19, ISSUE 5, P384-390.e1, May 2018

Can Bisphosphonates Prevent Recurrent Fragility Fractures? A Systematic Review and Meta-Analysis of Randomized Controlled Trials

  • Sang Yoon Lee
    Department of Rehabilitation Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea

    Seoul National University Institute on Aging, Seoul, Republic of Korea
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  • Se Hee Jung
    Department of Rehabilitation Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
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  • Shi-Uk Lee
    Department of Rehabilitation Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea

    Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
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  • Yong-Chan Ha
    Department of Orthopedic Surgery, Chung-Ang University College of Medicine, Seoul, Republic of Korea
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  • Jae-Young Lim
    Address correspondence to Jae-Young Lim, MD, PhD, Department of Rehabilitation Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 13620, Republic of Korea.
    Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

    Department of Rehabilitation Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea
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      Although a few trials have explored whether bisphosphonates (BPs) prevented recurrent fragility fractures (FFs), little is known about the secondary preventative effects of BPs. Thus, we performed a meta-analysis to examine the effects of BPs on prevention of subsequent fractures, mortality, and on bone metabolic and functional parameters related to FF. We compared BP and control groups.


      A meta-analysis of randomized controlled trials was conducted.

      Setting and Participants

      Twelve randomized controlled trials that included 5670 participants investigating the effects of BPs following FF were retrieved from PubMed, Embase, and the Cochrane Library.


      We performed a pairwise meta-analysis using fixed- and random-effects models.


      BPs exhibited significant secondary preventative effects after FF compared with controls [overall standardized mean difference = 0.766; 95% confidence interval (CI) 0.493–1.038; P < .001]. The risks of subsequent fracture (odds ratio = 0.499; 95% CI 0.418–0.596; P < .001) and mortality (odds ratio = 0.662; 95% CI 0.511–0.858; P = .002) decreased in the BP groups. Bone mineral density, bone turnover marker levels, pain at the fracture site, and health-related quality of life also differed significantly between the groups.


      Our meta-analysis revealed that BPs administered after FF potentially prevented subsequent fractures and reduced mortality. Positive effects in terms of pain, quality of life, and increased bone mineral density and bone metabolism were also verified regardless of the fracture sites and the administration types (oral or intravenous). Therefore, more active BPs use is recommended to prevent recurrent fragility fractures.

      Level of Evidence

      Level I, meta-analysis.


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