Background/Purpose: Dysregulation of osteoclast activity and uncontrolled bone resorption are hallmarks of multiple myeloma and metastatic prostate cancer, predisposing patients to net bone loss and pathologic fractures. Zoledronic acid, a bisphosphonate, induces osteoclast apoptosis and reduces bone resorption, reducing fracture risk, but the optimal dosing interval is the subject of current clinical debate. Historically, the standard dosing interval has been every 4 weeks, but recent research demonstrated no difference in the rate of skeletal-related events (SREs)—fracture, spinal compression, bone irradiation, or surgery—when zoledronic acid was dosed every 12 weeks. The primary objective of this study was to determine if extending the zoledronic acid dosing interval would increase the incidence of SREs in a Veteran population.
Methods: Retrospective observational analysis of multiple myeloma and prostate cancer patients who received zoledronic acid. Patients were stratified by zoledronic acid dosing interval (standard or extended). Baseline data, duration of treatment, type and incidence of SREs, and incidence of osteonecrosis of the jaw (ONJ) were determined for each group. Pearson’s chi-square test was used to determine statistical significance.
Results: One hundred twenty-three patients were eligible for inclusion based on prespecified criteria. No difference in the rate of SREs was found between the standard- and extended-interval dosing groups (30.6% vs 22.9%, P = 0.374). All instances of ONJ occurred in the standard-interval dosing group, but the difference in incidence between groups was not statistically significant (2.5% vs 0%, P = .347). Subgroup analysis did not reveal a difference between multiple myeloma and metastatic prostate cancer in the incidence of SREs (42.9% vs 14.3%, P = .172; and 28% vs 25%, P = .753, respectively) or ONJ (4.8% vs 0%, P = .451; and 2% vs 0%, P = .577, respectively).
Conclusions/Impliacations: Based on our results, extending the zoledronic acid dosing interval does not increase the incidence of SREs. Dosing zoledronic acid every three months offers a potential avenue to increase Veteran compliance and decrease the chance for adverse drug reactions without compromising therapeutic benefit.