Diagnostic and prognostic validity of serum bone turnover markers in metastatic renal cell carcinoma.
OBJECTIVE
We assessed the diagnostic accuracy of bone markers in the serum of patients with renal cell carcinoma to detect bone metastases and evaluate the prognostic potential concerning renal cell carcinoma caused mortality.


METHODS
The bone formation markers total and bone specific alkaline phosphatase, the bone resorption markers cross-linked N-terminal and tartrate-resistant acid phosphatase isoenzyme 5b, and the osteoclastogenesis markers osteoprotegerin and ligand of the receptor activator of nuclear factor-kappaB, were measured in the serum of 72 patients with renal cell carcinoma, including 28 with pN0M0, 8 with pN1M0 and 36 with M1, and in 32 female and 36 male controls by enzyme-linked immunosorbent assay techniques. Data were evaluated by receiver operating characteristics and survival analysis.


RESULTS
Bone specific alkaline phosphatase, tartrate-resistant acid phosphatase isoenzyme 5b and ligand of the receptor activator of nuclear factor-kappaB did not significantly differ between patients with renal cell carcinoma and controls. Compared with controls tartrate-resistant acid phosphatase isoenzyme 5b, cross-linked N-terminal and osteoprotegerin showed increased concentrations in patients with nonbone metastases but not in those with bone metastases. No bone turnover marker led to differentiation between patients with nonbone and bone metastases. Increased osteoprotegerin above the upper 95% cutoff limit, tumor stage and distant metastatic spread were associated with renal cell carcinoma related survival on Kaplan-Meier analyses. A multivariate Cox proportional hazards regression model revealed that these 3 variables were independent prognostic factors for cancer related death.


CONCLUSIONS
Bone turnover markers are hardly useful to diagnose bone metastases in patients with renal cell carcinoma. However, osteoprotegerin together with clinicopathological characteristics may be helpful as prognosticator of cancer specific death.
Jung
Klaus
K
Department of Urology, University Hospital Charité, Humboldt University of Berlin, Berlin, Germany. jung@charite.de
Lein
Michael
M
Ringsdorf
Martin
M
Roigas
Jan
J
Schnorr
Dietmar
D
Loening
Stefan A
SA
Staack
Andrea
A
D000135:Acid Phosphatase / Q000097:blood; D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001859:Bone Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000556:secondary; D016723:Bone Remodeling / Q000502:physiology*; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000556:secondary; D002352:Carrier Proteins / Q000097:blood; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007527:Isoenzymes / Q000097:blood; D007680:Kidney Neoplasms / Q000097:blood* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D015203:Reproducibility of Results; D012189:Retrospective Studies; D000071681:Tartrate-Resistant Acid Phosphatase
D015415:Biomarkers; D002352:Carrier Proteins; D006023:Glycoproteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase