Effect of single-dose dexamethasone on acute phase response following zoledronic acid: a randomized controlled trial

Abstract

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 5mg intravenously for the first time. Participants received oral dexamethasone 4mg (n=20) or placebo (n=20) at the time of ZOL infusion. Oral temperature was measured at baseline and three times a day for 3days following infusion. Symptoms of APR were assessed via questionnaire at baseline then daily for 3days and again at day 15 post-infusion. Use of rescue medications (paracetamol or ibuprofen) in the 3days 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 3days 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 4mg does not influence the incidence or severity of APR following first exposure to ZOL. ACTRN12615000794505.