Denosumab-associated hypocalcaemia: incidence, severity and patient characteristics in a tertiary hospital setting

作者：Huynh Andrew Liem Hieu; Baker Scott Thomas; Stewardson Andrew James; Johnson Douglas Forsyth

来源：Pharmacoepidemiology and Drug Safety, 2016, 25(11): 1274-1278.

DOI：10.1002/pds.4045

<jats:title>Abstract</jats:title><jats:sec><jats:title>Purpose</jats:title><jats:p>Denosumab‐associated hypocalcaemia (DAH) has been reported in patients with osteoporosis or metastatic bone disease and is associated with stages 4 and 5 chronic kidney disease (CKD, estimated glomerular filtration rate &lt;30 mL/min/1.73m<jats:sup>2</jats:sup>). Other risk factors for hypocalcaemia have not been fully elucidated.</jats:p><jats:p>We aimed to investigate the incidence of hypocalcaemia amongst patients receiving denosumab and to identify clinical features associated with this adverse event.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Retrospective cohort study between June 2013 and June 2014 of patients administered denosumab (60/120 mg) at a tertiary hospital in Melbourne, Australia, to identify the incidence of an albumin‐adjusted serum calcium concentration &lt;2.10 mmol/L or ionized calcium &lt;1.13 mmol/L within 6 months of treatment. Univariable and multivariable logistic regression analyses were performed to identify clinical features associated with DAH.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>One hundred and fifty‐five patients were administered denosumab (100 osteoporosis, 55 bone metastases). Twenty‐two patients (14% [95%CI 9.1–20.7]) developed hypocalcaemia: 55% were men, and 55% had osteoporosis. Eighty‐six per cent had a 25‐hydroxyvitamin D concentration &gt;50 nmol/L, and 91% were on calcium/colecalciferol supplementation. Stages 4 and 5 CKD (adjusted odd ratio [aOR] 4.71, 95%CI 1.61–13.79, <jats:italic>p</jats:italic> = 0.005) and male sex (aOR 4.30, 95%CI 1.69–10.96, <jats:italic>p</jats:italic> = 0.002) were associated with DAH. No patients were documented as having hypocalcaemic symptoms. One patient received intravenous calcium gluconate treatment.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The incidence of denosumab‐associated hypocalcaemia was 14% (95%CI 9.1–20.7) within 6 months of treatment despite widespread use of appropriate calcium/colecalciferol supplementation. Stages 4 and 5 CKD and male sex were associated with subsequent hypocalcaemia.

• 出版日期2016-11