The scientists observed that when cancer is present in bone, secretions from the tumor cells cause the osteoclasts to shift into high gear, so bone is destroyed more rapidly than it can be replenished. Coinciding with the changes in the bone the team identified a significant neurochemical change in the area of the spinal cord associated with the communication of pain signals to the brain. This change was closely correlated with an increase in the pain-related behaviors of the subject. The results suggested that accelerated osteoclastic activity is directly responsible for bone cancer pain. Mantyh and Clohisy hypothesized that by stopping the osteoclastic activity in the bone they might arrest the chemical changes in the spinal cord.
Several substances are effective in blocking osteoclastic activity.
In deciding which substance to use, the researchers sought one that would both block the osteoclasts and offer a clear understanding of the mechanism by which it did so. Over several months of testing, OPG was shown to rapidly block osteoclastic activity in the animal models. Most significantly, said Mantyh, the chemical changes in the spinal cord that are thought to amplify pain signals from the cancerous bone were also blocked, as were the pain-related behaviors. The results suggested that OPG, or drugs with similar activity, may provide an effective remedy for bone cancer pain. By working closely with Clohisy's lab, we have made a breakthrough in understanding the biological mechanism of pain related to bone deterioration.