Over the last two decades there have been significant de-velopments in the pharmacotherapy of osteoporosis. The thera-peutic arsenal has expanded with monoclonal antibodies which have been... Show moreOver the last two decades there have been significant de-velopments in the pharmacotherapy of osteoporosis. The thera-peutic arsenal has expanded with monoclonal antibodies which have been developed based on discoveries of the molecular mechanisms underlying bone resorption and bone formation. Denosumab, the antibody binding RANKL, inhibits bone resorp-tion, and romosozumab, the antibody binding sclerostin, inhibits bone resorption and stimulates bone formation as well. Both an-tibodies have shown potent anti-fracture efficacy in randomized clinical trials and this review will discuss the preclinical and clinical studies focusing on the effects on bone mass. After discontinuation of these antibodies, bone mineral density quickly returns to baseline and in the case of denosumab, discontinuation can not only induce rebound bone loss, but also the occurrence of vertebral fractures. Therefore, sequential antiresorptive therapy to maintain bone mass gains and anti-fracture efficacy is of utmost importance and will also be discussed in this review. (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/). Show less