title: Preadmission Bisphosphonate and Mortality in Critically Ill Patients.
abstract: Increased bone resorption predicts mortality and bone resorption heightens during critical illness. Bisphosphonates are potent inhibitors of bone resorption. Whether bisphosphonate impacts clinical outcome of intensive care unit (ICU) admission is unknown.
  
  
  
  We investigated the relationship between preadmission bisphosphonate use and clinical outcome in critically ill patients.
  
  
  
  This was a retrospective hospital-based analysis.
  
  
  
  The study was conducted at a tertiary referral hospital ICU.
  
  
  
  A total of 7830 critically ill patients between 2003 and 2014 participated in the study.
  
  
  
  The intervention included bisphosphonate treatment.
  
  
  
  In-hospital mortality in the main study (n = 7830) and bone density loss and biochemical and hematological changes in the mechanistic substudy (n = 111) were measured.
  
  
  
  A total of 245 patients received preadmission bisphosphonate. Bisphosphonate users were older (66 ± 16 vs 58 ± 18 y, P < .01) and had greater comorbid disease burden (Charlson comorbidity index: 5.7 ± 3.6 vs 4.6 ± 3.8, P < .01), yet bisphosphonate use was associated with a lower in-hospital mortality (mortality rate ratio: 0.41, 95% confidence interval 0.24-0.71, P < .01), which remained significant after adjusting for age, sex, principal diagnosis, admitting unit, comorbidities and admission year. Bisphosphonate-associated survival benefit was independent of vitamin D, but bisphosphonate/vitamin D co-use was associated with additive reduction in mortality (mortality rate ratio 0.38, 95% confidence interval 0.20-0.71, P < .01). Bone density decreased during ICU admission (-13% ± 19% per week, P < .01) but was significantly attenuated among bisphosphonate users compared with nonusers (-3% ± 13% per week v. -15% ± 14% per week, P < .01), despite similar disease severity on admission. All bisphosphonate users in the substudy survived, whereas six nonusers died.
  
  
  
  Preadmission bisphosphonate use was associated with superior survival among critically ill patients. Prospective studies examining the effects of bisphosphonate in critical illness are required.
authors.affiliation: Department of Endocrinology (P.L., J.A.E., J.R.C.), Department of Pharmacy (C.N.), Intensive Care Unit (P.N.), Department of PET and Nuclear Medicine (A.S.), St Vincent's Hospital, Division of Diabetes and Metabolism (P.L.), Division of Bone Biology (J.A.E., J.R.C.), Garvan Institute of Medical Research, and Faculty of Medicine (P.L., P.N., J.A.E., J.R.C.), University of New South Wales; and School of Medicine (P.L., J.A.E.), University of Notre Dame, Sydney, New South Wales 2010, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Lee
authors.affiliation: Department of Endocrinology (P.L., J.A.E., J.R.C.), Department of Pharmacy (C.N.), Intensive Care Unit (P.N.), Department of PET and Nuclear Medicine (A.S.), St Vincent's Hospital, Division of Diabetes and Metabolism (P.L.), Division of Bone Biology (J.A.E., J.R.C.), Garvan Institute of Medical Research, and Faculty of Medicine (P.L., P.N., J.A.E., J.R.C.), University of New South Wales; and School of Medicine (P.L., J.A.E.), University of Notre Dame, Sydney, New South Wales 2010, Australia.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ng
authors.affiliation: Department of Endocrinology (P.L., J.A.E., J.R.C.), Department of Pharmacy (C.N.), Intensive Care Unit (P.N.), Department of PET and Nuclear Medicine (A.S.), St Vincent's Hospital, Division of Diabetes and Metabolism (P.L.), Division of Bone Biology (J.A.E., J.R.C.), Garvan Institute of Medical Research, and Faculty of Medicine (P.L., P.N., J.A.E., J.R.C.), University of New South Wales; and School of Medicine (P.L., J.A.E.), University of Notre Dame, Sydney, New South Wales 2010, Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Slattery
authors.affiliation: Department of Endocrinology (P.L., J.A.E., J.R.C.), Department of Pharmacy (C.N.), Intensive Care Unit (P.N.), Department of PET and Nuclear Medicine (A.S.), St Vincent's Hospital, Division of Diabetes and Metabolism (P.L.), Division of Bone Biology (J.A.E., J.R.C.), Garvan Institute of Medical Research, and Faculty of Medicine (P.L., P.N., J.A.E., J.R.C.), University of New South Wales; and School of Medicine (P.L., J.A.E.), University of Notre Dame, Sydney, New South Wales 2010, Australia.
authors.forename: Priya
authors.initials: P
authors.lastname: Nair
authors.affiliation: Department of Endocrinology (P.L., J.A.E., J.R.C.), Department of Pharmacy (C.N.), Intensive Care Unit (P.N.), Department of PET and Nuclear Medicine (A.S.), St Vincent's Hospital, Division of Diabetes and Metabolism (P.L.), Division of Bone Biology (J.A.E., J.R.C.), Garvan Institute of Medical Research, and Faculty of Medicine (P.L., P.N., J.A.E., J.R.C.), University of New South Wales; and School of Medicine (P.L., J.A.E.), University of Notre Dame, Sydney, New South Wales 2010, Australia.
authors.forename: John A
authors.initials: JA
authors.lastname: Eisman
authors.affiliation: Department of Endocrinology (P.L., J.A.E., J.R.C.), Department of Pharmacy (C.N.), Intensive Care Unit (P.N.), Department of PET and Nuclear Medicine (A.S.), St Vincent's Hospital, Division of Diabetes and Metabolism (P.L.), Division of Bone Biology (J.A.E., J.R.C.), Garvan Institute of Medical Research, and Faculty of Medicine (P.L., P.N., J.A.E., J.R.C.), University of New South Wales; and School of Medicine (P.L., J.A.E.), University of Notre Dame, Sydney, New South Wales 2010, Australia.
authors.forename: Jacqueline R
authors.initials: JR
authors.lastname: Center
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000502:physiology*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016638:Critical Illness / Q000401:mortality*; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D017052:Hospital Mortality; D006760:Hospitalization; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates