Investigations on bone metabolism of urological tumors forming metastases

Bone metastases of urological tumors occur in nearly 40% of all primary tumors of the prostate, the kidney and the bladder. The quality of metastases may be described as osteolytic, osteoplastic or mixed lesion. Whereas prostate cancers produce mainly osteoplastic lesions, renal cell carcinomas predominantly generate osteolytic lesions. In bladder cancer both forms of metastases occur in tantamount numbers. However, diagnostics still presents many difficulties, since it is not feasible to identify very small metastases until symptoms have manifested themselves. The purpose of our study was to evaluate measurement technique and classification of significant serum markers for monitoring the course of disease. Patients with primary urological tumors and metastases in the skeleton were investigated and compared with healthy volunteers. Osteodensitometry was used to confirm and to replace radiological diagnosis of bone metastases. Thus it was possible to locate the extent and obtain information on the maximum charge and the stability of metastases. Our examinations revealed that distinct serum markers describe the changes in bone evoked by metastases. In comparison with healthy volunteers, patients with osteoplastic lesions and osteolytic lesions showed increases in hydroxproline and pyridinium crosslinks (significance at least p < 0.005). Osteocalcin was elevated only in osteoplastic lesions versus healthy volunteers (p < 0.01). For diagnostics of osteoplastic and osteolytic metastases, either alkaline phosphatase or the skeleton-specific phosphatase (ostase) can be measured serologically. Both parameters showed significant elevation in the patient groups when set against the healthy controls (both p < 0.0001). Compared with lytic lesions osteoplastic carcinomas revealed significant increase of alkaline phosphatase (p < 0.0001) and osteocalcin (p < 0.005). In examination of bone metabolism in patients with skeletal metastases the following parameters are of eminent interest: osteocalcin, hydroxyproline or pyridinium crosslinks, alkaline phosphatase or ostase. These serological parameters could be helpful even with regard to early diagnosis of bone metastases. Evaluation of measuring techniques suggests quantifying pyridinium crosslinks instead of hydroxyproline, because they may be assessed without taking the patient's diet into account. Determination of bone density may be helpful in diagnostics or control of therapy modalities.