Significance of serum osteoprotegerin and receptor activator of nuclear factor [kappa]B ligand in Japanese prostate cancer patients with bone metastasis

We aimed to assess the diagnostic accuracy of serum osteoclastogenesis markers for detection of bone metastasis in patients with prostate cancer (PCa) and to assess the usefulness of these markers as predictors of mortality from PCa. Serum osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) levels were measured in 201 patients (51 with bone metastasis, 55 with T2M0 PCa, 46 with T3M0 PCa, and 49 without PCa). Multivariate stepwise logistic regression analysis was used to identify independent predictors of bone metastasis. Correlation of serum marker levels with bone metastasis was assessed using receiver operating characteristics (ROC) analysis. Multivariate Cox proportional hazards analysis was used to predict cause-specific survival in PCa patients with bone metastasis. Serum OPG and prostate-specific antigen levels were significantly elevated in patients with bone metastasis. Multivariate stepwise logistic regression analysis demonstrated that serum OPG levels were significant predictors of bone metastasis. ROC analyses showed that serum OPG levels were the most reliable predictor of bone metastasis (area under the curve = 0.68). Multivariate Cox proportional hazards analysis revealed that only serum OPG and extent of disease on bone scan (EOD) >3 were independent prognostic factors for PCa-related death. On the other hand, serum RANKL levels were not significant predictors of bone metastasis and could not predict survival probability in PCa patients with bone metastasis. Serum OPG was a more reliable marker than serum RANKL in detecting bone metastatic spread and in predicting survival probability in PCa patients with bone metastasis.[PUBLICATION ABSTRACT]