Treatment for osteoporosis is usually long term, so it is often necessary to implement a sequential treatment strategy. The clinician must know not only how to select the best available therapy in each clinical situation, but also how to discontinue or change treatment at a certain point in the evolution of the disease. Here, we briefly review the mechanisms of action and the consequences of discontinuing each of the drugs for osteoporosis, as well as what happens with the different treatment sequences. Discontinuation of denosumab has clearly negative consequences for the skeleton, and only bisphosphonates, due to its particular remaining antiresorptive effect, could be discontinued for a limited time (drug holidays). Switching from antiresorptive to another antiresorptive with a different mechanism of action is an option that may be favorable in the management of some patients with osteoporosis. Switching from antiresorptive to anabolic may be associated with an initial bone mineral density loss that does not appear to have negative consequences on antifracture efficacy. Starting with anabolic (teriparatide or romosozumab) and subsequently switching to antiresorptive is the best treatment sequence, so it could be the preferred option in patients who present a very high risk of fracture.
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