Upon cessation of denosumab (DMAB) treatment, there is a marked acceleration in bone remodeling leading to notable bone degradation. This intensified bone remodeling has been quite often associated with a rebound increase in fracture risk. Consequently, some clinicians recommend continuous and indefinite DMAB administration. However, potential adverse effects or certain conditions might necessitate the discontinuation of DMAB. Additionally, in certain patients, bone mineral density (BMD) may have reached a threshold where the continuation of DMAB no longer offers significant reductions in fracture risk. It is imperative for patients discontinuing DMAB to transition to alternative anti-osteoporosis therapy, with meticulous monitoring, particularly within the initial year when the majority of bone loss typically occurs. Current research is investigating the efficacy of treatments such as zoledronate and oral bisphosphonates post-DMAB cessation. There is also emerging real-world evidence highlighting the impact of sequential medications, like raloxifene or romosozumab on preserving BMD in these patients. The benefits of sequential treatment can vary based on the duration of prior DMAB therapy. In all scenarios, transitioning to another anti-osteoporosis therapy is essential, although the ideal therapeutic regimen remains to be elucidated.