Patients with high-risk limited prostate cancer (PCa) are at high risk of developing bone metastases (BMs). Denervation therapy (ADT) is the standard of care for metastatic PCa, but in denervation-resistant patients, zoledronic acid (ZA) can significantly reduce the incidence of bone-related complications of PCa. Recently, Manfred et al. from the University Hospital Gustav in Dresden investigated the efficacy of zoledronic acid in preventing bone metastases in patients with high-risk non-metastatic PCa and published the article in a recent issue of the European Urology journal. The results found that intravenous zoledronic acid every three months for four years did not prevent the development of bone metastases. The study included 1433 patients with PCa who had at least one of the following three high-risk factors: GLeason score 8-10; positive lymph nodes; PSA ≥20 ng/ml. exclusion criteria were visceral metastases or bone metastases, history of bisphosphonates, chemotherapy treatment, etc. Subjects were randomized to the zoledronic acid and control groups: patients in the zoledronic acid group received zoledronic acid plus standard depot therapy, with zoledronic acid administered intravenously at 4 mg every three months for no more than 4 years. In the control group, patients received only depot treatment. The researchers used a bone imaging procedure (BIP) to detect the occurrence of bone metastases and to assess the occurrence and timing of bone metastases, overall survival, and adverse events between the groups. A total of 1040 patients in the study completed the four-year BIP, which showed 88 bone metastases in the zoledronic acid group (17.1%) compared with 89 in the control group (17.0%), a negligible difference. Radiological indicators of bone metastases were hot spots on bone scans, and further imaging revealed that 94 of these 177 (53%) did have bone metastases. After 4.8 years of follow-up (median time), Kaplan-Meier survival analysis found no significant difference in the time to bone metastases and overall survival between the zoledronic acid and control groups. Adverse events were 78.9% and 74.1% in the zoledronic acid and control groups, respectively. Most of the adverse events were mild, but musculoskeletal disorders were more frequent in the zoledronic acid group. Zoledronic acid has been shown to be of great benefit in PCa patients with debulking resistance and bone metastases, and the European Society of Urology guidelines recommend its routine use in debulking-resistant prostate cancer as a means of suppressing bone metastasis-related events. However, this study found no significant difference in the incidence of bone metastases between the zoledronic acid and control groups, with the incidence of radiologically diagnosed bone metastases in the zoledronic acid and control groups being 17.1% and 17%, respectively, over 4 years. In addition, the benefit of zoledronic acid did not appear to be as good as expected given the complications associated with zoledronic acid treatment. Although this study had population heterogeneity and methodological limitations, it suggests that zoledronic acid injections of 4 mg every three months for 4 years are not effective in suppressing the development of bone metastases in patients with high-risk nonmetastatic PCa. The use of zoledronic acid in this population needs to be studied in more depth.