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Many experts regard drug holidays as an integral part of the long-term use of oral bisphosphonates in the management of osteoporosis. Such holidays are made possible by the very long residence time in bone of bisphosphonates and are considered to be desirable because long-term continuous use of oral bisphosphonates results in increasing rates of atypical femoral fractures (AFF). Short breaks in bisphosphonate use might circumvent this problem without increasing the risk of osteoporotic fractures, and they also reduce patients’ medication burden.
Bisphosphonates are complex phosphate salts which bind avidly to the surface of bone, where they remain with half-lives measured in years. Drug absorption following oral administration is only about 1% with the absorbed drug rapidly taken up onto the bone surface or excreted in the urine over the following few hours. Bisphosphonates on bone surfaces impair osteoclast function, reducing bone resorption and leading to modest increases in bone density. Fracture risk is reduced (approximate reductions in non-vertebral and hip fractures of 25% and 40%, respectively and by up to 70% in verterbral fractures) and remains low over at least a decade of treatment.1 2
Effect of stopping bisphosphonates on bone activity and fractures
Following discontinuation of alendronate, biochemical markers of bone turnover increase modestly over 1–2 years, returning to pretreatment baseline levels in some studies but not in others.1 3 Hip bone density returns towards its pretreatment level over the following 5 years.2 The offset of effect is related to the avidity of bone binding of each drug, as well as its potency, dose and duration of use, so the effects of the low-avidity bisphosphonates, risedronate and ibandronate, tend to be more transient and those of zoledronate most durable, exceeding 5 years.4–7 A year after risedronate …
Competing interests None declared. Refer to the online supplementary files to view the ICMJE form(s).
Provenance and peer review Commissioned; externally peer reviewed.
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