Multiple Vertebral Fractures after Denosumab Discontinuation: How to Avoid Them? Abstract. Denosumab is a monoclonal antibody raised against the RANK ligand that inhibits the maturation and activity of osteoclasts. It decreases bone resorption, increases bone density and reduces fracture risk. However, after its discontinuation, a significant rebound effect appears that lasts about two years. It results in increased markers of bone remodeling, a loss of bone density that may be greater than gain, and an increased risk of multiple vertebral fractures. These fractures occur at a frequency of 1 to 10 %. Due to this high risk, denosumab should be a second-line treatment limited to very specific indications. At denosumab discontinuation, in order to limit the rebound effect, the current recommendation is to prescribe a strong bisphosphonate (alendronate, zoledronate) and regularly monitor the bone resorption markers.