Effect of a three-day course of dexamethasone on acute phase response following treatment with zoledronate: a randomized controlled trial.

Zoledronate is a potent intravenous bisphosphonate effective in the management of osteoporosis, Paget's disease and skeletal-related events in malignancy. Its most frequent adverse effect is the acute phase response (APR), an inflammatory reaction characterized by fever, musculoskeletal pain, headache, and nausea. This randomized, placebo-controlled, double-blind study investigated the efficacy of a three-day course of dexamethasone 4 mg daily in reducing incidence of APR. Participants (N = 60) were randomized to receive either 4 mg of oral dexamethasone one and a half hours before zoledronate and once a day for the following two days, or placebo. Oral temperature was measured at baseline and three times a day for the following three days, and questionnaires assessing symptoms of the APR were completed at baseline and for three days following zoledronate. Use of anti-inflammatory medication in the three days following zoledronate was recorded. The primary outcome was the temperature change from baseline. There was a significant difference in the primary outcome between the dexamethasone and placebo groups (p < 0.0001), with a mean decrease in temperature of 0.10 °C (95% CI -0.34, 0.14) in the dexamethasone group compared with a mean increase in temperature of 0.84 °C (95% CI 0.53, 1.16) in the placebo group on the evening following zoledronate. There was also a difference in APR-related symptom score over time between the two groups (p = 0.0005), with a median change in symptom score in the dexamethasone group one day after zoledronate of 0 (95% CI 0, 1) compared with 3 (95% CI 0, 5) in the placebo group. An increase in temperature of ≥1 °C to a temperature of >37.5 °C occurred in 2/30 (6.7%) participants in the dexamethasone group compared with 14/30 (46.7%) in the placebo group (p = 0.0005). This study demonstrates that a three-day course of dexamethasone substantially reduces the acute phase response following zoledronate infusion. This article is protected by copyright. All rights reserved.