title: Denosumab-associated hypocalcaemia: incidence, severity and patient characteristics in a tertiary hospital setting.
abstract: 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 <30 mL/min/1.73m2). Other risk factors for hypocalcaemia have not been fully elucidated. We aimed to investigate the incidence of hypocalcaemia amongst patients receiving denosumab and to identify clinical features associated with this adverse event.
  
  
  
  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 <2.10 mmol/L or ionized calcium <1.13 mmol/L within 6 months of treatment. Univariable and multivariable logistic regression analyses were performed to identify clinical features associated with DAH.
  
  
  
  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 >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, p = 0.005) and male sex (aOR 4.30, 95%CI 1.69-10.96, p = 0.002) were associated with DAH. No patients were documented as having hypocalcaemic symptoms. One patient received intravenous calcium gluconate treatment.
  
  
  
  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. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of General Medicine, Austin Health, Heidelberg, Victoria, Australia. andrew.huynh@austin.org.au.
authors.forename: Andrew Liem Hieu
authors.initials: AL
authors.lastname: Huynh
authors.affiliation: Department of General Medicine, Austin Health, Heidelberg, Victoria, Australia.|Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Scott Thomas
authors.initials: ST
authors.lastname: Baker
authors.affiliation: Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Andrew James
authors.initials: AJ
authors.lastname: Stewardson
authors.affiliation: Department of General Medicine, Austin Health, Heidelberg, Victoria, Australia.|Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Douglas Forsyth
authors.initials: DF
authors.lastname: Johnson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002118:Calcium / Q000008:administration & dosage / Q000097:blood*; D002762:Cholecalciferol / Q000008:administration & dosage; D015331:Cohort Studies; D000069448:Denosumab / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006996:Hypocalcemia / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D015994:Incidence; D008297:Male; D051436:Renal Insufficiency, Chronic / Q000150:complications; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D062606:Tertiary Care Centers; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D050071:Bone Density Conservation Agents; D014807:Vitamin D; D002762:Cholecalciferol; D000069448:Denosumab; C104450:25-hydroxyvitamin D; D002118:Calcium
keywords: chronic kidney disease; denosumab; hypocalcaemia; metastatic bone disease; osteoporosis; pharmacoepidemiology