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Risk of Fractures with Glitazones

A Critical Review of the Evidence to Date

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Abstract

The insulin-sensitizing thiazolidinediones (commonly known as glitazones) are an important and widely prescribed class of antidiabetic agents. Glitazones exert their action through activation of proliferator-activated receptor gamma (PPAR-γ) nuclear transcription factor and are effective drugs to achieve glycaemic control in patients with type 2 diabetes mellitus. Recent rapidly growing evidence suggests that glitazone use is associated with accelerated bone loss and an increased risk of fracture. This review aims to evaluate the current knowledge of adverse effects of glitazone therapy on the skeleton. Articles in English, Spanish, German and French published up until April 2009 are included. Results from preclinical studies have demonstrated that activation of PPAR-γ inhibits bone formation by primarily diverting mesenchymal stem cells to the adipocytic rather than to the osteogenic lineage, and that glitazones may increase bone resorption by stimulating osteoclasts. Numerous studies in humans have demonstrated decreased bone turnover, accelerated bone loss and impaired bone mineral density both in healthy volunteers and in patients with type 2 diabetes. Furthermore, results from recent large, randomized controlled trials and from observational studies provided evidence for an increased fracture risk for glitazone users, mostly for women, but possibly also for men. As a consequence of these observations, clinicians should carefully assess the fracture risk in patients with type 2 diabetes before starting therapy with glitazones.

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Acknowledgements

No sources of funding were used to assist in the preparation of this review. Christoph Meier has undertaken consultant work for Takeda Pharmaceuticals, the manufacturer of one of the drugs discussed in this review, and has received grants and has grants pending for epidemiological studies involving pioglitazone and other drugs produced by Takeda Pharmaceuticals. The other authors have no conflicts of interest that are directly relevant to the content of this review.

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Authors and Affiliations

  1. Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Hebel-strasse 2, CH-4031, Basel, Switzerland

    Michael Bodmer &  Christoph R. Meier

  2. Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Basel, Basel, Switzerland

    Christian Meier & Marius E. Kraenzlin

  3. Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, Lexington, Massachusetts, USA

    Christoph R. Meier

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  1. Michael Bodmer
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  2. Christian Meier
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Correspondence to Christoph R. Meier.

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Bodmer, M., Meier, C., Kraenzlin, M.E. et al. Risk of Fractures with Glitazones. Drug-Safety 32, 539–547 (2009). https://doi.org/10.2165/00002018-200932070-00001

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