title: Time Course of Calcium Concentrations and Risk Factors for Hypocalcemia in Patients Receiving Denosumab for the Treatment of Bone Metastases From Cancer.
abstract: BACKGROUND
  Severe hypocalcemia sometimes develops during denosumab treatment for bone metastases from cancer and is, therefore, an important issue. However, limited information is available on the risk factors for hypocalcemia and the appropriate interval for monitoring serum calcium concentration.
  
  
  OBJECTIVE
  The present study aimed to identify the risk factors for grade ≥2 hypocalcemia and to investigate the time course of serum calcium concentrations in patients receiving denosumab for bone metastases from cancer.
  
  
  METHODS
  The medical records of 66 cancer patients treated with denosumab between April 2012 and August 2013 were retrospectively reviewed.
  
  
  RESULTS
  Of the 66 enrolled patients, 11, 5, and 1 developed grade 1, 2, and 3 hypocalcemia, respectively. All 4 patients with a baseline estimated glomerular filtration rate (eGFR) of <30 mL/min developed hypocalcemia. Hypocalcemia occurred in only 20%, 24%, and 15% of patients with an eGFR of 30 to 59, 60 to 89, and ≥90 mL/min, respectively. Multivariate logistic regression analysis revealed that lower eGFR values (odds ratio, 1.72 per 10 mL/min decrease, P = 0.02) were significantly associated with grade ≥2 hypocalcemia. In 11 patients who developed hypocalcemia during the first treatment course, the mean calcium concentrations decreased from 9.8 mg/dL at baseline to 8.4 mg/dL during the first week and reached a nadir of 8.1 mg/dL during the second week.
  
  
  CONCLUSIONS
  Our results support more frequent monitoring of serum calcium concentrations at baseline and during the first 2 weeks of treatment in patients receiving denosumab, especially those with an eGFR <30 mL/min.
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan ikesue@pharm.med.kyushu-u.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ikesue
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Koujiro
authors.initials: K
authors.lastname: Hata
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Mishima
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Mayako
authors.initials: M
authors.lastname: Uchida
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Egashira
authors.affiliation: Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Miyamoto
authors.affiliation: Department of Comprehensive Clinical Oncology, Faculty of Medical Sciences, Kyushu University.
authors.forename: Eishi
authors.initials: E
authors.lastname: Baba
authors.affiliation: Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University.
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takayama
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
authors.affiliation: Department of Comprehensive Clinical Oncology, Faculty of Medical Sciences, Kyushu University.
authors.forename: Eriko
authors.initials: E
authors.lastname: Tokunaga
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Okamoto
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University.
authors.forename: Akira
authors.initials: A
authors.lastname: Yokomizo
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University.
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University.
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Satohiro
authors.initials: S
authors.lastname: Masuda
keywords: denosumab; glomerular filtration rate; hypocalcemia; kidney dysfunction; risk factor