The Effect of Prophylactic Use of NSAIDs on Acute Phase Reactions Induced by First-Time Zoledronic Acid Treatment for Osteoporosis

Abstract

Background:

Zoledronic acid is a first-line treatment for primary osteoporosis, but its high acute-phase-reaction (APR) incidence can reduce patient compliance and long-term efficacy. Non-steroidal anti-inflammatory drugs (NSAIDs), with antipyretic and analgesic effects, can relieve APR symptoms like fever and muscle soreness caused by zoledronic acid. However, the role of prophylactic NSAID use in decreasing APRs remains controversial.

Objective:

This study aims to evaluate the impact of NSAIDs on preventing zoledronic acid-related APRs to guide clinical practice.

Methods:

Retrospective data of osteoporosis patients receiving zoledronic acid injection at Shenzhen University General Hospital from January 2023 to December 2024 were collected. A 1:2 propensity score matching (PSM) compared the APR incidences between the non-NSAIDs and NSAIDs groups.

Results:

Among 351 cases (98 non-NSAIDs, 253 NSAIDs), 200 cases (79 non-NSAIDs, 121 NSAIDs) remained after PSM. The NSAIDs group had a lower overall APR incidence (38.0% vs. 53.2%, χ² = 4.451, P = .035). There was no significant difference in fever incidence (χ2 = 1.888, P = .169), but pain incidence was lower in the NSAIDs group (25.3% vs. 9.9%, χ² = 8.433, P = .004). Flurbiprofen axetil, ibuprofen, and etoricoxib showed similar APR—preventive effects.

Conclusion and relevance:

Prophylactic NSAIDs significantly reduce zoledronic acid-induced APRs, especially pain, but have no significant effect on preventing fever. The 3 NSAIDs also have comparable efficacy.