The aim of the present study was to compare a novel marker for high bone turnover with two routine markers for screening in prostate cancer patients. The markers were evaluated in two studies: (a) a cross-sectional study of 170 prostate cancer patients with local disease stratified by +/-lymph node metastases (N 0, N1) compared with controls and (b) a longitudinal study of 40 hormone refractory prostate cancer patients stratified by skeletal involvement and followed during docetaxel (+/-BM) and zoledronate (+BM) treatment. Presence or absence of bone metastases (BM) was assessed by imaging techniques (magnetic resonance imaging or X-ray) and technetium-99m scintigraphy. The serum or urinary levels of alpha C-telopeptide of collagen type I (alphaalphaCTX), prostate-specific antigen (PSA), and total alkaline phosphatase (tALP) were assessed. PSA was elevated in both N 0 and N1 patients compared with controls, whereas alphaalphaCTX was elevated only in N1 patients. tALP exhibited no difference in any of the groups. In the treatment study, PSA decreased with treatment in both the -BM and +BM groups compared with baseline values, showing similar effect of docetaxel or docetaxel/zoledronate treatment on this marker. On the contrary, alphaalphaCTX and tALP did not decrease with docetaxel treatment in the -BM group compared with baseline, whereas it decreased significantly with docetaxel/zoledronate treatment in the +BM group, already after 1 month of treatment for alphaalphaCTX. Results suggest that alphaalphaCTX is superior to PSA and tALP for identifying patients having a high risk of metastatic disease and for monitoring skeletal progression in +BM prostate cancer patients during treatment