Study: Osteoporosis drug reduces bone loss, tumor size in oral cancer

December 13, 2010

COLUMBUS, Ohio - 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 an important supplemental therapy in patients with head and neck cancers that erode bone.

In this Ohio State University study, the drug treatment also was associated with smaller tumors - an unexpected result.

The drug, zoledronic acid, is known by the brand name Zometa. It is designed to inhibit bone resorption, the breaking down of bone caused by the release of a specific kind of cell.

Oral squamous cell carcinoma accounts for about 90 percent of all tumors in the mouth. The five-year survival rate for this form of cancer is 61 percent for all stages combined, according to the National Cancer Institute.

When these tumors form in the gums, their growth in the limited space of 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. So even though bone loss itself is not life-threatening, loss of bone means the tumor is continuing to grow.

"The goal is to stop the vicious cycle," said Thomas Rosol, professor of veterinary biosciences at Ohio State and senior author of the study. "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 assure the drug's safety and effectiveness, he said.

The research is published in a recent issue of the journal Cancer Research.

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 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 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."

Rosol also noted that in the course of this research, an Ohio State graduate student developed the first mouse model of oral squamous cell carcinoma that leads to bone loss. Chelsea Martin, lead author of the study and a doctoral student in veterinary biosciences at the time, determined which kinds of cancer cells to use and where to inject them to produce the same cancer development in mice that is experienced by human patients.

"This new model mimics the disease very well," Rosol said.

It turns out that oral squamous cell carcinoma is also a common disease in cats. Knowing this, Martin, now a postdoctoral researcher in molecular and cellular biochemistry at Ohio State, produced the animal disease model by injecting oral cancer cells from a cat into the gums above the front teeth of mice whose immune systems were suppressed.

Rosol and colleagues plan to continue the research by testing the effects of zoledronic acid when it is combined with anticancer drugs in animals with head and neck cancer.
-end-
This work was supported by grants from the Morris Animal Foundation, the National Cancer Institute and the National Institutes of Health.

Additional co-authors of the paper include Jillian Werbeck, Nanda Thudi, Lisa Lanigan and Tobie Wolfe of veterinary biosciences, and Ramiro Toribio of veterinary clinical sciences, all at Ohio State.

Contact: Thomas Rosol, (614) 292-4265; rosol.1@osu.edu

Written by Emily Caldwell, (614) 292-8310; caldwell.151@osu.edu

Ohio State University

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.