title: Comparison of 10 serum bone turnover markers in prostate carcinoma patients with bone metastatic spread: diagnostic and prognostic implications.
abstract: Our aim was to assess the diagnostic accuracy of bone markers in serum of patients with prostate cancer (PCa) for early detection of bone metastases and their usefulness as predictors of PCa-caused mortality. In sera of 117 PCa patients (pN0M0, n = 39; pN1M0, n = 34; M1, n = 44), 35 healthy men and 35 patients with benign prostatic hyperplasia, bone formation markers [total and bone-specific alkaline phosphatase (tALP, bALP), amino-terminal procollagen propeptides of type I collagen (P1NP), osteocalcin (OC)], bone resorption markers [bone sialoprotein (BSP), cross-linked C-terminal (CTX) and cross-linked N-terminal (NTX) telopeptides of type I collagen, tartrate-resistant acid phosphatase isoenzyme 5b (TRAP)] and osteoclastogenesis markers [osteoprotegerin (OPG), receptor activator of nuclear factor kappaB ligand (RANKL)] were measured. tALP, bALP, BSP, P1NP, TRAP, NTX and OPG were significantly increased in PCa patients with bone metastases compared to patients without metastases. OPG showed the best discriminatory power to differentiate between these patients. Logistic regression analysis resulted in a model with OPG and TRAP as variables that predicted bone metastasis with an overall correct classification of 93%. Patients with concentrations of OPG, P1NP, tALP, bALP, BSP, NTX, TRAP and CTX above cut-off levels showed significantly shorter survival than patients with low marker concentrations. Multivariate Cox proportional hazards regression revealed that only OPG and BSP were independent prognostic factors for PCa-related death. Thus, the importance of serum OPG in detecting bone metastatic spread, alone or in combination with other bone markers, and predicting survival in PCa patients has been clearly demonstrated.
authors.affiliation: Department of Urology, University Hospital Charité, Humboldt University of Berlin, Berlin, Germany. klaus.jung@charite.de
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.forename: Michael
authors.initials: M
authors.lastname: Lein
authors.forename: Carsten
authors.initials: C
authors.lastname: Stephan
authors.forename: Katharina
authors.initials: K
authors.lastname: Von Hösslin
authors.forename: Axel
authors.initials: A
authors.lastname: Semjonow
authors.forename: Pranav
authors.initials: P
authors.lastname: Sinha
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Loening
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schnorr
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001859:Bone Neoplasms / Q000473:pathology* / Q000556:secondary*; D001862:Bone Resorption; D002277:Carcinoma / Q000473:pathology* / Q000556:secondary*; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000473:pathology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor; D012044:Regression Analysis; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human