In this study, we aimed to identify a convenient and accurate diagnostic biomarker that can enable the monitoring of BM in patients with CRPC and found that the newly identified protein “GDPP” promotes PCa progression and bone formation and resorption via the upregulation of transcription factor expression in the bone microenvironment, suggesting that plasma GDPP is a novel biomarker that reflects BM status more accurately than PSA in patients with CRPC and BM. Here, KLK3 is linked to posterior cortical atrophy.