Evaluation des Knochenstoffwechsels anhand verschiedener Resorptions- und Formationsmarker im Serum bei Patienten mit lokalisiertem und fortgeschrittenem Prostatakarzinom

The subject of this MD thesis was the prospective analysis of the relevance of four different serum markers of bone turnover in different stages of prostate cancer in the assessment of bone metastases. Alkaline phosphatase (ALP) and Osteocalcin (OC) represent bone formation and Tartrate-resistant acide phosphatase type 5b (TRACP5b) and Serum-C-terminal telopeptide of type I collagen (CTX) represent bone resorption. This study included 219 men, 129 undergoing radical retropubic prostatectomy (RRP), 25 with bone metastases due to prostate cancer, and 65 with benign urological disorders who served as controls. Men undergoing RRP were divided in lymph node negative and lymph node positive groups. It was shown that, apart from CTX, all markers (ALP, TRACP5b and OC) were significantly increased in serum blood samples from patients with bone metastases, with ALP and TRACP5 having the highest values. The controls had the lowest marker levels. Patients with lymph node positive cancer had significantly high serum levels of TRACPb and ALP, but not for OC and CTX. So far it is known that bone metastases are of the osteoblastic typ. Our data suggest that both osteoblastic and osteoclastic processes are actually involved in the development of bone metastases. For the first time ever we were able to show significantly increased values for both bone formation and bone resorption markers in patients with lymph node metastases. Lymph node positive patients with radical retropubic prostatectomy are high risk patients (pT3, Gleason >8, N+) and hence have a high risk of progression or developing metastases. Surprisingly, patients with localized stage prostate cancer and a clean szintigramm of the bones already show increased serum TRACP5b (p<0,005) and serum ALP (p<0,05). With the help of ALP it was possible to clearly differ between lymph node positive and lymph node negative patients. As one might expect, the pre-operative PSA values were much higher with these patients as with lymph node negative patients. This findings underline the value of PSA as a predictive marker for advanced prostate cancer. A longitudinal study of the patients should answer the question if and when lymph node negative patients with increased serum TRACP5b and ALP are developing bone metastases. In this setting adjuvant bisphosphonates might inhibit osteoblastic and osteoclastic activity and hence delay or even prevent manifestation of bone metastases. Unexpectedly, serum TRACP5b was also significantly increased in lymph node negative patients. The clinical relevance of this finding and a possible therapeutic option can also be investigated with a longitudinal study. This study shows that markers of bone turnover are reliable markers for patients with bone metastases and also are promising markers for early detection of bone metastases, maybe earlier than conventional radiological methods.