Effect of a Three‐Day Course of Dexamethasone on Acute Phase Response Following Treatment With Zoledronate: A Randomized Controlled Trial

ABSTRACT 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 1.5 hours before zoledronate and once a day for the following 2 days, or placebo. Oral temperature was measured at baseline and three times a day for the following 3 days, and questionnaires assessing symptoms of the APR were completed at baseline and for 3 days following zoledronate. Use of anti‐inflammatory medication in the 3 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 37.5°C occurred in two of 30 (6.7%) participants in the dexamethasone group compared with 14 of 30 participants (46.7%) in the placebo group (p = 0.0005). This study demonstrates that a 3‐day course of dexamethasone substantially reduces the APR following zoledronate infusion. © 2023 American Society for Bone and Mineral Research (ASBMR).