Rebound-associated vertebral fractures (RVFx) following denosumab discontinuation are typically multiple, are commonly associated with acute sharp pain, increase the risk of imminent fractures, and are pathogenetically different from common osteoporotic vertebral fractures (VFx). A clinically relevant question is whether patients with RVFx should be managed differently from patients with osteoporotic VFx. To address this question, we performed a systematic search of the PubMed database, and we reviewed current evidence on the optimal management of patients with RVFx. For pain relief of patients with RVFx, potent analgesics, often opioids, are essential. Information on the effectiveness of braces in these patients is scarce. Vertebroplasty and kyphoplasty are strongly contraindicated as they confer a substantial risk for new VFx. Exercise may be helpful, but again evidence is lacking. In contrast to patients with osteoporotic VFx, in whom initial treatment with bone-forming agents is recommended, patients with RVFx should initiate treatment with potent antiresorptives. To summarize, patients who have sustained RVFx following denosumab discontinuation are at a very high risk for new fractures, especially VFx. The management of such patients requires a multidisciplinary approach that should not be restricted to pain relief and administration of antiosteoporotic medication, but should also include back protection, early mobilization, and appropriate exercise.