The Role of Bisphosphonate Drug Holidays in the Management of Osteoporosis

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.