Predictors of Hypocalcemia Induced by Denosumab in Patients with Bone Metastases: A Prospective Cohort Study

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K18114
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy; Orthopaedic surgery
• Research Institution: Showa University
• Principal Investigator: Ishikawa Koji 昭和大学, 医学部, 助教 (40794946)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: デノスマブ / 抗RANKLモノクローナル抗体 / 低Ca血症 / 骨転移 / 骨粗鬆症 / 骨代謝回転

Outline of Final Research Achievements

Hypocalcemia is the most common major adverse event in patients with bone metastasis receiving denosumab. In the present prospective study, we aimed to identify the risk factors of hypocalcemia. Although all patients received prophylactic administration (ALF: 1.0 ug and Ca: 600mg), 21.4 % and 2.4 % patients developed Grade1 and Grade2 hypocalcemia, respectively. It is possible that severe hypocalcemia was mitigated by oral supplementation. We also revealed that bone turnover markers are potentially useful for prediction of hypocalcemia following denosumab treatment in patients with bone metastasis. Routine measurement of serum calcium concentrations following denosumab is recommended for patients with high bone turnover for timely detection and early treatment initiation.

Free Research Field

整形外科、脊椎外科、骨粗鬆症、骨転移、骨代謝

Academic Significance and Societal Importance of the Research Achievements

担癌患者の骨転移を予防するために抗RANKL抗体は広く臨床で用いられている。
本研究における最大の意義は、骨代謝マーカーを用いることにより、抗RANKL抗体をより安全に投与することができるようになったということである。さらに、厳密に補充療法[活性型VitD製剤(ALF:1.0ug)とCa製剤(600mg)]を設定した研究も過去に少なく、補充療法を決める際の指標になる。投与時に高代謝回転を呈するような患者は十分な補充療法の元、血清Ca値のモニタリングが推奨される。