Zoledronic acid (ZA) is used in the treatment of bone metastasis. However, adverse effects associated with a typical 3- to 4-week schedule of ZA therapy prompted researchers to explore outcomes with a less-frequent schedule. Their findings were recently published in Critical Reviews in Oncology/Hematology.

From a literature review of randomized, controlled trials regarding the use of ZA in treatment of solid tumor-related bone metastasis, the investigators identified 3 phase 3 trials (N=2650 patients total) with information available on 4-week vs 12-week dosing schedules, adverse events (AEs), skeletal-related events (SREs), and skeletal morbidity rate (SMR).

Using these studies, the investigators performed a meta-analysis to compare SMRs, SREs, and AEs for therapy schedules involving ZA injections given either every 4 weeks or every 12 weeks.

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The 12-week and 4-week ZA therapy schedules showed similar rates of both SMR (rate ratio [RR], 0.97; 95% CI, 0.84-1.13) and SREs (RR, 1.02; 95% CI, 95% CI, 0.89-1.16). The 4-week schedule was associated with a lower risk of surgery to bone (RR, 0.52; 95% CI, 0.32-0.86).

Regarding AEs, the investigators reported a clinically relevant advantage with the 12-week schedule of ZA compared with the 4-week schedule (RR, 1.17; 95% CI, 1.06-1.29). The 4-week schedule was associated with a higher rate of discontinuation (RR, 1.61; 95% CI, 1.17-2.21).

The results led the investigators to conclude that in some settings of bone metastasis, the 12-week ZA injection schedule may be a suitable alternative to the 4-week schedule, especially for patients who are susceptible to hypocalcemia or renal failure.


Santini D, Galvano A, Pantano F, et al. How do skeletal morbidity rate and special toxicities affect 12-week versus 4-week schedule zoledronic acid efficacy? A systematic review and a meta-analysis of randomized trials. Crit Rev Oncol Hematol. 2019;142:68-75.

This article originally appeared on Oncology Nurse Advisor