Objectives To correlate serum levels of bone markers with pain levels and extent of skeletal disease (EOD), in patients suffering from prostate cancer with bone only metastases. Methods Thirty-six males with hormone-refractory prostate carcinoma, bone only metastases and no history of therapies, drugs, or diseases that affect bone metabolism were studied. Karnofsky performance status, pain scoring, EOD, osteocalcin (OC), prostate-specific antigen, bone alkaline phosphatase amino-terminal and carboxy-terminal propeptides and telopeptides of type I collagen were analysed. Twenty-four healthy controls of the same age were also established. Results With only the exception of OC, bone marker values of patients were significantly increased compared with the upper reference limits (P < 0.0001 for bone alkaline phosphatase and amino-terminal telopeptide of type I collagen, 0.012 for amino-terminal propeptide of type I collagen, 0.0023 for carboxy-terminal propeptide of type I collagen, and 0.04 for carboxy-terminal telopeptide of type I collagen). All bone markers and prostate-specific antigen also showed significant paired correlations (P <= 0.019) and linear increases with advancing EOD (P <= 0.032). Finally, none of the measured markers correlated significantly with pain levels. Conclusion Bone markers are remarkably elevated in the serum of prostate cancer patients with metastatic bone disease and correlate with EOD. Paired correlations also suggest an accelerated but proportional (coupled) bone metabolism. Nucl Med Commun 31: 249-253 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.