Hormonal therapies for receptor positive-breast and prostate cancer patients have shown clinical efficacy but also several side effects including osteoporosis, loss of bone mass and increased fracture risk. Denosumab represents an anti RANKL (receptor activator of nuclear factor-kB ligand) monoclonal anti-body acting as inhibitor of osteoclasts formation, function, and survival, then increasing bone mass. Herein, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the role of Denosumab in saving bone health in prostate and breast cancer patients receiving respectively androgen deprivation therapy and adjuvant endocrine therapy. Moreover, selected patients have to be treated with Denosumab at the dose of 60 mg every six month or placebo. Outcomes studied included the bone mass density (BMD) increase at 24 and 36 months, BMD loss, reduction of fractures risk (in particular vertebral) at 24 and 36 months and safety (overall, serious adverse events - SAEs and discontinuation rate). Our results showed a reduction of the BMD loss up to 36 months both at the lumbar and femoral level and a BMD increase both at 24 and 36 months. It was also found a reduction in the number of new vertebral and femoral fractures at 24 and 36 months. Finally, our pooled analysis showed that Denosumab did not affect both the SAEs and therapy discontinuation risk. In conclusion, Denosumab administration can be considered effective and safe in the prevention and management of the above mentioned adverse events related to hormonal therapies designed for breast and prostate tumors.