BACKGROUND: Breast and prostate cancer patients often develop lesions of locally high bone turnover, when the primary tumor metastasizes to the bone causing an abnormal high bone resorption at this site. The objective of the present study was to determine whether local increased bone turnover in breast and prostate cancer patients is associated with an increase in cartilage degradation and to test in vitro whether osteoclasts or cathepsin K alone generate CTXII from human bone. METHODS: The study included 132 breast and prostate cancer patient, where presence of bone metastases was graded according to the Soloway score. Total bone resorption (CTXItotal) and cartilage degradation (CTXII) were determined. RESULTS: Breast and prostate cancer patients with bone metastases revealed significant increased levels of CTXItotal at Soloway scores 1 and higher compared to patients without bone metastases (p < 0.001). CTXII was statistically elevated at score 3 and 4 (p < 0.01). CTXII/CTXItotal significantly decreased at score 3 and 4 (p < 0.001). Levels of CTXItotal, CTXII and CTXII/CTXItotal changed +900%, +130%, and -90%, respectively at Soloway score 4 compared to score 0. The in vitro experiments revealed that osteoclasts released CTXI fragments but not CTXII from bone specimens. The same was observed for cathepsin K. CONCLUSION: Data suggest that an uncoupling between bone resorption and cartilage degradation occurs in breast and lung cancer patient.