Background: Zoledronic acid (ZA) eventually reduces risk of skeletal morbidity carries beneficial effect on bone pain. Moreover, ZA eventually extends a period to bone pain and the SRE onset after CRPC (castration-resistant prostate cancer) and improves the QOL of the patients. ZA, therefore, has become a standard supportive therapy for CRPC with bone metastasis. However, it remains unclear when the physicians should start ZA treatment for prostate cancer (PCa) patients with bone metastasis. In the present study, we investigated whether we could extend a period before androgen sensitive PCa with bone metastasis becoming CRPC by ZA treatment. Methods: The patients were randomly classified in two groups (combined androgen blockade (CAB) alone group and CAB + ZA treatment group) based on Gleason score (less than 7 or more) EOD score (less than 2 or more). Four mg ZA treatment was conducted every 4 weeks. We evaluated serum PSA value, bone-related markers, and SRE. The first end point was a period before androgen sensitive PCa with bone metastasis becoming CRPC. Results: Untreated 59 PCa patients with bone metastasis were enrolled by 2011 from 2006. Thirty patients were classified in the CAB alone group and 29 patients in the CAB + ZA group. There were no significant difference in age (72,5 and 71.7 yo, respectively), PSA (381.3 ng/ml and 399.0 ng/ml, respectively), Gleason score, and EOD score between CAB alone group and CAB + ZA group. Although there was no significant difference in PSA-progression free survival (PFS) (p=0.14), tendency that CAB + ZA shows better PFS than CAB alone group was observed (time to 50% PFS was extended 9.4 months than CAB alone group). Moreover, the sub analysis using the patients with more than Gleason score 7 or with more than EOD score 1, CAB +ZA group showed better PFS (p=0.074 in Gleason score and p=0.028 in EOD score. Conclusions: This result indicates that CAB with ZA from initial treatment can extend a period before PCa, especially high advanced PCa recurring.