CTSK and neoplasm: In a previous study we found that the levels of type I collagen carboxy-terminal telopeptide (ICTP), generated by MMP-1 cleavage of type I collagen, increased significantly with disease progression in bone and were not influenced by bisphosphonate therapy in contrast to the N-telopeptide (NTx, an amino-acid epitope cleaved by osteoclastic cathepsin K activity), leading to the hypothesis that a mechanism that is not inhibited by bisphosphonates, therefore osteoclast-independent, can contribute to tumor-induced bone osteolysis [39].