title: Effect of single-dose dexamethasone on acute phase response following zoledronic acid: a randomized controlled trial.
abstract: Zoledronic acid provokes an inflammatory reaction, or acute phase response, in some individuals. We examined whether treatment with dexamethasone could prevent this response. A single dose of dexamethasone 4 mg, given at the time of zoledronic acid infusion, did not influence the incidence or severity of the acute phase response.
  
  
  
  The potent bisphosphonate zoledronic acid (ZOL) is used to treat osteoporosis, Paget's disease, and hypercalcemia of malignancy. This medication can provoke an inflammatory reaction, known as the acute phase response (APR). We examined whether glucocorticoid treatment at the time of first exposure to ZOL prevents the development of APR.
  
  
  
  This double-blind, randomized, controlled trial assessed 40 adults receiving ZOL 5 mg intravenously for the first time. Participants received oral dexamethasone 4 mg (n = 20) or placebo (n = 20) at the time of ZOL infusion. Oral temperature was measured at baseline and three times a day for 3 days following infusion. Symptoms of APR were assessed via questionnaire at baseline then daily for 3 days and again at day 15 post-infusion. Use of rescue medications (paracetamol or ibuprofen) in the 3 days following infusion was evaluated. Primary outcome was between-group difference in temperature change from baseline.
  
  
  
  There was no significant difference in temperature change (p = 0.95) or symptom score (p = 0.42) in the 3 days following ZOL between dexamethasone and placebo recipients. Eleven (55%) in the dexamethasone group and 10 (50%) placebo recipients experienced a temperature increase of ≥1 °C (p = 0.99). Seven (35%) in the dexamethasone group and 9 (45%) in the placebo group experienced an increase in symptom score of ≥3 points (p = 0.75). Thirteen (65%) dexamethasone recipients and 12 (60%) in the placebo group required rescue medications (p = 0.99). Dexamethasone was well-tolerated.
  
  
  
  A single dose of dexamethasone 4 mg does not influence the incidence or severity of APR following first exposure to ZOL.
  
  
  
  ACTRN12615000794505.
authors.affiliation: Bone & Joint Research Group, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand. emma.billington@ahs.ca.|Division of Endocrinology and Metabolism, University of Calgary, 1820 Richmond Road SW, Calgary, Alberta, T2T 5C7, Canada. emma.billington@ahs.ca.
authors.forename: E O
authors.initials: EO
authors.lastname: Billington
authors.affiliation: Bone & Joint Research Group, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
authors.forename: A
authors.initials: A
authors.lastname: Horne
authors.affiliation: Bone & Joint Research Group, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
authors.forename: G D
authors.initials: GD
authors.lastname: Gamble
authors.affiliation: Bone & Joint Research Group, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
authors.forename: K
authors.initials: K
authors.lastname: Maslowski
authors.affiliation: Bone & Joint Research Group, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
authors.forename: M
authors.initials: M
authors.lastname: House
authors.affiliation: Bone & Joint Research Group, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
authors.forename: I R
authors.initials: IR
authors.lastname: Reid
mesh_terms: D000210:Acute-Phase Reaction / Q000139:chemically induced / Q000517:prevention & control*; D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects*; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D005938:Glucocorticoids; D007093:Imidazoles; D000077211:Zoledronic Acid; D003907:Dexamethasone
keywords: Acute phase response; Anti-inflammatory; Dexamethasone; Osteoporosis; Zoledronic acid