The Role of Bisphosphonate Drug Holidays in the Management of Osteoporosis

Authors

  • Sandra Kim, MD, FRCPC Division of Endocrinology & Metabolism, Women’s College Hospital Department of Medicine, University of Toronto Graduate Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto
  • Adrian Lau, MD, FRCPC Division of Endocrinology & Metabolism, Women’s College Hospital Department of Medicine, University of Toronto

DOI:

https://doi.org/10.58931/cdet.2024.2331

Abstract

Osteoporosis is a chronic skeletal disorder of compromised bone strength leading to an increased risk of fragility fractures, particularly with advancing age. More than 2 million Canadians are living with osteoporosis, and osteoporotic fractures are associated with considerable morbidity, increased mortality, and high economic burden to the healthcare system. The ultimate goal of osteoporosis pharmacotherapy is to reduce the risk of fragility fractures.

Bisphosphonates are the most widely used first-line medications for osteoporosis due to their robust anti-fracture efficacy and favourable safety profile, as demonstrated in short-term randomized placebo-controlled trials of 3-years duration with fracture outcome assessed as the primary endpoint. However, the optimal duration of bisphosphonate therapy has been questioned regarding their long‑term efficacy and safety given their long half‑life in bone. Prolonged use is associated with very rare but serious adverse complications such as atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ). Moreover, while extension trials indicate that long‑term bisphosphonate therapy helps maintain bone density, the evidence supporting further fracture risk reduction with prolonged treatment is less convincing. Regarding concerns about rare adverse effects and the attenuated benefit-to-risk ratio with long‑term use, several professional organizations have issued guidelines suggesting bisphosphonate drug holidays. This approach aims to minimize prolonged exposure and mitigate rare risks while preserving some residual anti-fracture benefits from the persistent drug in the skeleton. Here, we review the role of bisphosphonate drug holidays in the long-term management of osteoporosis, the supporting evidence, recommended guidelines on treatment duration, along with key considerations for implementing a bisphosphonate drug holiday.

Author Biographies

Sandra Kim, MD, FRCPC, Division of Endocrinology & Metabolism, Women’s College Hospital Department of Medicine, University of Toronto Graduate Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto

Dr. Sandra Kim is an Associate Professor and Clinician Teacher in Department of Medicine and Division of Endocrinology & Metabolism at the University of Toronto. She is the current Division Head of Endocrinology at Women’s College Hospital and past Medical Director of the Osteoporosis Program. Her clinical and academic focus is on osteoporosis and metabolic bone disease. She was the past chair of the Scientific Advisory Council for Osteoporosis Canada and the current chair of their guidelines committee. She led the pharmacotherapy working group for the 2023 Canadian Osteoporosis Clinical Practice Guideline update and serves on the Canadian Panel for the International Society for Clinical Densitometry. Dr. Kim is actively involved in teaching at both the undergraduate and postgraduate levels and is the recipient of several awards. She is also involved with the Ontario Osteoporosis Strategy in providing osteoporosis care to underserviced communities via telemedicine.

Adrian Lau, MD, FRCPC, Division of Endocrinology & Metabolism, Women’s College Hospital Department of Medicine, University of Toronto

Dr. Adrian Lau obtained his medical degree at the University of Toronto, where he also completed his postgraduate training in Internal Medicine, and Endocrinology and Metabolism. Subsequently, he obtained his Masters of Science in Community Health (Health Practitioner Teacher Education program) at the University of Toronto. Currently, he is an Assistant Professor and Clinician Teacher in the Division of Endocrinology and Metabolism at Women’s College Hospital. His particular clinical interests are in osteoporosis and metabolic bone diseases. He is actively involved in teaching at both the undergraduate and postgraduate levels. He currently serves on the Scientific Advisory Council of Osteoporosis Canada, and the Canadian regional panel of the International Society for Clinical Densitometry.

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Published

2024-11-25

How to Cite

Kim, S., & Lau, A. (2024). The Role of Bisphosphonate Drug Holidays in the Management of Osteoporosis. Canadian Diabetes & Endocrinology Today, 2(3), 12–20. https://doi.org/10.58931/cdet.2024.2331

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