Osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF) are very rare adverse events in bisphosphonate users and even more rare in denosumab users.
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Extending bisphosphonate treatment beyond 3–5 years does not confer additional benefit in low-risk populations.
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Treatment re-initiation (usually 1–3 years after bisphosphonate withdrawal) depends on risk factors, new fractures and bone mineral density.
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The evidence regarding denosumab discontinuation is limited but caution is advised, as there may be a “rebound effect” with regard to fractures.
Abstract
Background
Bisphosphonates and denosumab are used extensively in the treatment of postmenopausal osteoporosis. Despite their proven efficacy in the reduction of vertebral and non-vertebral fractures, their optimal duration of use has not been determined. The occurrence of adverse effects, such as osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF), has raised the issue of bisphosphonate or denosumab discontinuation (“drug holiday”) after a certain treatment period.
Aim
To assess the effect of bisphosphonate and denosumab discontinuation on fracture risk, as well as its possible benefits in reducing the risk of adverse effects.
Methods
Systematic review and consensus of expert opinion.
Results and conclusions
Discontinuation of bisphosphonates should be considered in all patients who have been treated for more than five years with alendronate, risedronate or zoledronic acid. In view of the limited evidence, no robust recommendations can be made for ibandronate and denosumab. If the patient has not experienced fractures before or during therapy and the fracture risk is low, a “drug holiday” can be recommended. Although there is no solid evidence, 1–2 years for risedronate, 3–5 years for alendronate and 3–6 years for zoledronic acid are suggested. After this time, the patient should be reassessed. If a new fracture is experienced, or fracture risk has increased or BMD remains low (femoral neck T-score ≤−2.5), anti-osteoporotic treatment should be resumed. In the case of denosumab discontinuation, close monitoring is suggested, due to the possibility of rebound fractures.