Animals treated with the drug retained twice as much total bone as did mice with cancer that were untreated. The bone that was present after treatment was a combination of reduced loss of pre-existing bone and an increase in new bone formation, said Rosol, also an investigator in Ohio State's Comprehensive Cancer Center.
Powerful images of the animals' skulls revealed that the bone loss was so severe in some untreated animals with cancer that their tooth roots were exposed. In comparison, animals with cancer that received the drug retained enough bone to keep the tooth roots covered with bone. Overall, on average, mice with cancer that received the drug treatment retained enough bone to match the amount of total bone in mice without tumors.
"When there is bone loss, there is formation of new bone to try to compensate for the loss," Rosol said. "The new bone is not perfect, but importantly, drug treatment prevented loss of both pre-existing normal bone and the new bone that formed."
The retention of bone was attributed at least in part to the drug's ability to reduce the number of activated osteoclasts by 52 percent at sites where the tumor and bone met. Osteoclasts are the cells that are responsible for bone resorption.
The cancer cells that were injected into the mice had been altered to contain a protein that creates light so the scientists could track development of the tumors. At day 28, the tumors treated with zoledronic acid were, on average, at least 14 percent smaller than were tumors that were left untreated.
"With less bone resorption, there might be less stimulation of the tumor," Rosol said. "So if you slow down bone loss, it's no
|Contact: Thomas Rosol|
Ohio State University