Zoledronic acid, a drug currently approved for osteoporosis treatment, has been shown to reduce bone loss in a study of mice with oral cancer, suggesting it could serve as a supplemental therapy in patients with head and neck cancers that erode bone (Cancer Research, November 1, 2010, Vol. 70:21, pp. 8607-8616).
The drug, known by the brand name Zometa, is designed to inhibit bone resorption.
Oral squamous cell carcinoma accounts for about 90% of all tumors in the mouth, according to the National Cancer Institute. The five-year survival rate for this form of cancer is 61% for all stages combined.
When these tumors form in the gums, their growth in the mouth leads to bone loss in the jaw. In turn, bone erosion stimulates the cancer to grow. Scientists call this phenomenon, driven in part by the release of cancer stimulatory compounds from bone, a vicious cycle that occurs in this and other forms of cancer. Even though the bone loss itself is not life-threatening, loss of bone means the tumor is continuing to grow.
— Thomas Rosol, DVM, PhD, Ohio State
University
"The goal is to stop the vicious cycle," said Thomas Rosol, DVM, PhD, professor of veterinary biosciences at Ohio State, in a press release. "Chemotherapy, radiation, and surgery are all used to treat head and neck cancers. Zoledronic acid is a very safe drug and all it does is block bone resorption, so patients could receive all of the standard treatments, and this drug could be added as an additional benefit. That's the overall concept."
Further animal and human studies would be required to determine the proper dose and ensure the drug's safety and effectiveness, he said.
The researchers injected mice with oral squamous cell carcinoma cells from cats to create a disease model for the study. They assigned mice to one of four groups: animals with and without tumors that received a placebo treatment, and mice with and without tumors that received a zoledronic acid treatment.
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% at sites where the tumor and bone met.
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% 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 not as suitable an environment for the cancer to progress. We were not trying to cure the cancer, but what we're showing is that even with no other therapy than zoledronic acid, the disease is better."
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