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Identification of risk factors and development of detection algorithm for denosumab‐induced hypocalcaemia
Author(s) -
Imatoh Takuya,
Sai Kimie,
Takeyama Mayu,
Hori Katsuhito,
Karayama Masato,
Furuhashi Kazuki,
Segawa Katsunori,
Kimura Michio,
Kawakami Junichi,
Saito Yoshiro
Publication year - 2019
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.12753
Subject(s) - hypocalcaemia , denosumab , medicine , odds ratio , retrospective cohort study , context (archaeology) , confidence interval , medical record , algorithm , osteoporosis , calcium , paleontology , computer science , biology
Summary What is known and objective This study used electronic medical records to identify risk factors and establish a detection algorithm for denosumab‐induced hypocalcaemia. Methods We identified 201 patients with cancer who were initially prescribed denosumab. Hypocalcaemia was defined as an adjusted serum calcium level of ≤2.13 mmol/L. A diagnosis of denosumab‐induced hypocalcaemia was confirmed by two physicians after reviewing patient medical records. We evaluated patient characteristics as potential screening factors. Moreover, a retrospective cohort study was conducted to identify risk factors for denosumab‐induced hypocalcaemia. Odds ratios ( OR s) were estimated using logistic regression analysis. Results We analysed 164 patients with a low risk of hypocalcaemia. Among these, 29 (17.7%) patients were suspected to have denosumab‐induced hypocalcaemia. The times to onset of definitive hypocalcaemia were shorter among these patients than among patients with non‐denosumab‐induced hypocalcaemia. Based on receiver operating characteristic curve analysis, we used time to onset of hypocalcaemia of ≤90 days as a second screening factor. The positive predictive value of this factor was 87.5%. In the retrospective cohort study, a significant difference was observed among patients with serum alkaline phosphatase ( ALP ) levels of >5.95 μkat/L before initial prescription ( P < 0.01). Patients with higher serum ALP levels had a 6.63 times higher risk of developing hypocalcaemia than those without increased serum ALP levels ( OR : 6.63, 95% confidence interval [ CI ]: 1.79‐29.31). The same results were observed in a sensitivity analysis using another database. What is new and conclusion We developed a detection algorithm for denosumab‐induced hypocalcaemia based on calcium levels and time to onset of hypocalcaemia. We also identified elevated ALP levels as a risk factor for hypocalcaemia. Clinicians should carefully monitor initial serum calcium levels and screen for signs of hypocalcaemia in patients receiving denosumab who demonstrate elevated serum ALP levels.