For bone cancer patients, just the touch of a loved one or getting out of bed can produce excruciating pain.
The pain medications prescribed, which include morphine in later stages, provide only temporary relief and present debilitating side effects like sedation, loss of focus and constipation.
“This is probably one of the most intense pains that humans ever feel,” said Patrick Mantyh, University professor in preventative sciences and neurosystems.
“You have no life, you cannot sleep, you have difficulty holding a conversation and you don’t want to move out of your bed.”
Mantyh, an expert in the chemistry of pain, and Denis Clohisy, University professor in orthopaedic surgery, set out to find the cause of the pain and defeat it.
During their study, the results of which are printed in the May issue of Nature Medicine, the team discovered the cell that is responsible for bone destruction, pain in bone cancer patients and how it can be stopped.
“The goal of the study going in was to identify the mechanisms that generate bone cancer pain,” Mantyh said. “And once we understood the mechanisms, to try to develop new therapies based on that knowledge.”
There are several hundred thousand new cases of bone cancer reported each year. Most result from the spread of the disease from other sites, typically the breast or prostate.
Although survival is not expected in patients with bone cancer that has spread too far, they live between two and five years on average.
Mantyh said the pain associated with this disease and the side effects from the chronic use of pain medications are the most common complaints from patients.
“That’s a significant amount of time a person could be enjoying their life, as opposed to being sedated,” he said. “The hope is that this therapy is going to restore the quality of life for the individual and give the life back to the individual.”
To attack the cause of the pain, the researchers focused their approach on the cells in the body, which are responsible for the destruction and rebuilding of bones.
In healthy bones, there is a balance between these cells. One dissolves old bone and the other replenishes it.
In bone cancer patients, however, the cells that destroy the bone become overactive and out of control, while the replenishing cells are prevented from rebuilding new tissue.
In their research, Mantyh and Clohisy found that it was the overactive bone destruction that caused pain, and they hypothesized that if they could prevent this activity, they could prevent pain.
To do this, they chose osteoprotegrin, a naturally occurring compound in all humans, which in normal bones inhibits the destructive cells from working too quickly.
By introducing more of this compound into cancerous bones, they found that it would continue to slow destruction and therefore reduce pain.
This approach is attractive because it targets the specific cause of the pain, and because it is already found in the body, it has no known side effects.
Typical pain medications for bone cancer like morphine work, but they do not seek out the source of pain. Because in many cases they are strong drugs, side effects can result.
“It’s the difference between a single bullet and the shotgun approach, where you hope one of the pellets hits the problem,” Clohisy said. “But it also hits other things.”
Clohisy added while it will be several years before this treatment is available to patients, there is no reason to believe the compound’s effects won’t work in humans just as they do in animals.
In fact, the discovery of how bone pain is caused might lead to treatments for other types of skeletal pain, including fractures, osteoporosis and sickle cell anemia.
Tucker LeBien, deputy director of the University Cancer Center, said although much more research will have to be done, this pain-relief strategy could have long-term benefits for patients suffering from bone cancer pain.
“This is one of those wonderful type of collaborations that occur in a cancer center in a large public university, and we expect that kind of effort and outcome,” he said. “It’s really delightful to observe it.

Justin Costley covers the Medical School and welcomes comments at [email protected]. He can also be reached at (612) 627-4070 x3224.