Abstract: Denosumab is a novel monoclonal antibody targeted for the treatment of osteoporosis. Continued use of the drug results in sustained increases in bone mineral density, decreases in bone turnover, and reductions in the risk of systemic multiple fractures in osteoporosis patients. The anti-resorptive effect of denosumab for the bone is reversible. When the side-effects of the drug prompt the denosumab discontinuation in osteoporosis patients, the reversal is usually associated with marked increases in bone turnover and bone loss, further increasing the risk of fractures. Therefore, the patients should be given subsequent anti-osteoporosis therapy in time after stopping Denosumab during the initial year. This paper summarizes the research advances in the risks of denosumab discontinuation and related factors, metabolic mechanism, and subsequent coping strategies in pharmacological therapy for osteoporosis, so as to provide references for personalized and precise treatment on osteoporosis patients with denosumab discontinuation in clinical practice.