title: High serum ALP level is associated with increased risk of denosumab-related hypocalcemia in patients with bone metastases from solid tumors.
abstract: Metastatic bone disease is one of the most common complications of advanced cancers. Pathological fractures, spinal cord compression, and radiotherapy or surgery to the bone are collectively called skeletal-related events (SREs), which cause severe pain, increase hospitalization rates, and impair the quality of life (QOL) of patients with bone metastases. The receptor activator of nuclear factor-kB ligand (RANKL)/RANK pathway is critical in the progression of bone metastases. Previous studies have demonstrated that an anti-RANKL antibody (denosumab) was superior to zoledronic acid in prolonging time to first SRE in patients with bone metastases from prostate and breast cancers. However, severe hypocalcemic events occur more frequently after treatment with denosumab compared with zoledronic acid. In this study, 368 administrations of denosumab in 219 patients with metastatic bone disease from solid tumors were analyzed to clarify the risk factors for developing hypocalcemia. The results showed that grade 2/3 hypocalcemia was observed in 10.4% of the total number of denosumab administrations. Patients with higher baseline serum ALP, higher performance status (PS), or gastric cancer were at higher risk for developing hypocalcemia. The cut-off value for ALP to predict denosumab-related hypocalcemia was 587 U/L with a sensitivity of 0.77 and a specificity of 0.81. Close monitoring of serum calcium, especially after the first treatment with denosumab, is strongly recommended in these patients.
authors: Division of Nephrology & Endocrinology, Department of Medicine, the University of Tokyo Hospital, Tokyo, Japan.
authors: Yuka
authors: Y
authors: Kinoshita
authors: Makoto
authors: M
authors: Arai
authors: Nobuaki
authors: N
authors: Ito
authors: Yuichi
authors: Y
authors: Takashi
authors: Noriko
authors: N
authors: Makita
authors: Masaomi
authors: M
authors: Nangaku
authors: Yusuke
authors: Y
authors: Shinoda
authors: Seiji
authors: S
authors: Fukumoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy / Q000556:secondary*; D000069448:Denosumab / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006996:Hypocalcemia / Q000097:blood / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy / Q000473:pathology*; D012189:Retrospective Studies; D012307:Risk Factors; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D050071:Bone Density Conservation Agents; D000069448:Denosumab; D000469:Alkaline Phosphatase