This study explores the rebound phenomenon in a transgenic mouse model of osteoporosis expressing human RANKL (TgRANKL) and evaluates the impact of sequential zoledronate therapy.<h4>Methods</h4>TgRANKL mice were divided into four experimental groups: vehicle control, continuous denosumab treatment, denosumab withdrawal, and sequential denosumab followed by zoledronate, including an additional follow-up phase after zoledronate discontinuation. Here, TNFSF11 is linked to osteoporosis.