Serum osteoprotegerin and receptor activator of nuclear factor-kappa B ligand as indicators of disturbed osteoclastogenesis in patients with prostate cancer.

Abstract

We evaluated the behavior and diagnostic usefulness of the osteoclastogenesis proteins osteoprotegerin and receptor activator of nuclear factor-kappaB ligand (RANKL) in the serum of patients with prostate cancer (PCa). Serum osteoprotegerin and RANKL were retrospectively measured in 117 patients with prostate cancer, including 39 with stage pN0M0, 34 with stage pN1M0 and 44 with bone metastases, in 35 presumably healthy men and in 35 patients with benign prostatic hyperplasia (BPH). The association of these components with clinical data (tumor stage and grade) and receiver operating characteristics curves compared with the bone formation marker alkaline phosphatase and bone resorption marker crosslaps (cross-linked C-terminal telopeptides of type I collagen) were calculated. Osteoprotegerin was increased in patients with bone metastases, while those with localized cancer or lymph node metastases had values similar to those in presumably healthy controls and patients with BPH. RANKL did not differ among the control, BPH and PCa subgroups. Thus, the ratio of osteoprotegerin-to-RANKL showed behavior similar to that of osteoprotegerin. Osteoprotegerin and RANKL did not show any significant correlation with tumor stage, histological tumor grade, total prostate specific antigen, alkaline phosphatase activity or crosslaps. ROC analysis data proved that osteoprotegerin had a better diagnostic accuracy than alkaline phosphatase or crosslaps for detecting bone metastases in PCa cases. Serum osteoprotegerin but not RANKL indicates disturbed osteoclastogenesis in patients with PCa and bone metastatic spread. It could be used as a marker for bone metastases.