The second dosage of Denosumab associated with a significant rebound effect in the course of discontinuation, leads to BMD loss and enhances the risk of MSCVFs, evident from a report of the Journal of Current Osteoporosis Reports.

Denosumab, a human monoclonal antibody improves bone mineral density (BMD), decreases fracture risk and bone resorption. A 40%, 28%, and 68% reduction was seen in hip fracture risk, non-vertebral clinical fractures, and radiological vertebral fractures (VFs) risk in three years after the treatment. However, the discontinuation of Denosumab related to high risk of multiple vertebral fractures. Five current case series found with five median numbers of vertebral fractures within 7 to 20 months following the last Denosumab dose. This risk can be reduced by introducing a bisphosphonate before initiating Denosumab and/or after ceasing Denosumab. Although minimal case series evident these approaches.

As several uncertainties mark Denosumab discontinuation, it is considered as the second-line approach for osteoporosis management.