Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord

Bone cancer pain is common among cancer patients and can have a devastating effect on their quality of life. A chief problem in designing new therapie s for bone cancer pain is that it is unclear what mechanisms drive this dis tinct pain condition. Here we show that osteoprotegerin, a secreted 'decoy' receptor that inhibits osteoclast activity, also blocks behaviors indicati ve of pain in mice with bone cancer. A substantial part of the actions of o steoprotegerin seems to result from inhibition of tumor-induced bone destru ction that in turn inhibits the neurochemical changes in the spinal cord th at are thought to be involved in the generation and maintenance of cancer p ain. These results demonstrate that excessive tumor-induced bone destructio n is involved in the generation of bone cancer pain and that osteoprotegeri n may provide an effective treatment for this common human condition.