The anti-receptor activator of nuclear factor-kB ligand (RANKL) antibody denosumab is thought to be useful in the improvement of the quality of life of patients with bone metastasis from thoracic tumors, given the ease of its subcutaneous administration. However, attention has to paid to the onset of hypocalcemia when determining the optimal dosage, especially since data and methods on its prevention are limited. Our project team monitored serum calcium levels in patients receiving denosumab treatment, evaluated methods to supplement calcium and vitamin D in cases of hypocalcemia, and developed an evidence-based common manual. Subsequently, denosumab administration and hypocalcemia were evaluated as per the manual. Grade 3 hypocalcemia was observed in 2 cases before the preparation, with no new cases seen since adopting the new protocol in the manual. We conclude that the development of severe hypocalcemia associated with denosumab treatment can be avoided by prompt management of this condition in the early stages and by adopting measures listed in the practice manual.