Interval Comparison of Zoledronic Acid Treatment in Patients with Metastatic Bone Disease, Is 4-Weekly or 12-Weekly More Effective?: A Systematic Review and Meta-analysis

Objectives: The aim of bisphosphonate treatment in patients with metastatic bone disease is to prevent metastatic skeletal morbidity and prevent cancer treatment-induced skeletal damage. The classical recommendation of Zoledronic acid treatment is to be given indefinitely as intravenous infusion every 3 to 4 weeks until patients' health deteriorates. Data on zoledronic acid's long-term effectiveness and safety are insufficient, and some recent literatures start to consider 12-weekly administration as a reasonable alternative in order to minimize the adverse effects. Methods: A systematic search was conducted based on PRISMA guideline to identify relevant studies through PubMed, Google Scholar, and Cochrane database. A total of 5 studies (2867 patients) were included, divided into outcome analysis, processed using Review Manager 5.3. Results: The search of electronic databases yielded a total of 299 entries. Five studies were included in the qualitative and quantitative synthesis following the steps of identifying, screening, determining eligibility, eliminating duplicates, and excluding studies. Out of a total of 2.867 patients, 1.427 received ZA for 12 weeks and 1.440 received ZA for 4 weeks, making up the total number of patients included in this meta-analysis. Each trial had a comparable one-year follow-up duration after ZA was given. We discovered that the incidence of adverse effects varied significantly between the two groups. In contrast, there is no statistically significant difference in the rates of SRE, ONJ, renal dysfunction, or death between the two groups. Conclusion: Our systematic review and meta-analysis reveals that 12-week intervals of zoledronic acid is as effective as the standard 4-week interval in terms of skeletal related event, jaw osteonecrosis, renal dysfunction, and mortality rate. However, the standard 4-week intervals led to higher rate of adverse effects.