December 22, 2011
By David Martin
|Kim Templeton, MD (left); Rama Garimella, PhD; and Ossama Tawfik, MD, PhD, were among the members of a team that studied vitamin D's effect on osteosarcoma cells.|
A team of researchers at the University of Kansas Medical Center has shown that vitamin D turns malignant osteosarcoma cells into normal cells, making it potentially useful in the treatment of pediatric bone cancer. The finding appears in the Journal of Orthopaedic Research.
Kim Templeton, MD, began thinking several years ago about vitamin D and the role it might play in the treatment of osteosarcoma. A professor in the Department of Orthopedic Surgery at the KU School of Medicine, Templeton had been invited to join a group of experts in New York City to talk about recommended levels of vitamin D intake. Research has linked vitamin D deficiency to cancer and other diseases. Given that vitamin D is also instrumental in bone health, Templeton, the first surgeon in the United States to use titanium alloy rods to save the limbs of patients who've lost bones to cancer, left the conference wanting to explore its effect on osteosarcoma cell lines.
Osteosarcoma is a malignant bone tumor that predominantly affects children and adolescents. The cancer tends to occur in larger bones when the bones are growing the fastest. Between 500 and 800 cases are diagnosed in the United States each year.
Typically, osteosarcoma patients receive 10 weeks of chemotherapy before the tumor is removed surgically. Templeton says the chemotherapy regimen is not all that different from the one administered to patients 20 years ago. The survival rate — 60 to 70 percent of patients live five years after being diagnosed — is largely unchanged as well. "It's a cancer where we really need to find a better way to treat it, to add something else into the chemotherapy regimen," she says.
Templeton kicked around ideas with colleagues Ossama Tawfik, MD, PhD, a professor in the Department of Pathology and Laboratory Medicine, and Stephen Smith, MD, professor of pediatric hematology and oncology. Tawfik says he was excited to explore the idea that vitamin D could be used as a weapon against osteosarcoma. Vitamin D, Tawfik says, takes care of the cell. "If it's not there, bad things are going to happen," he says.
They assembled an interdisciplinary team of physicians and scientists with expertise ranging from bone biology to biostatistics. In the first arm of the study, Tawfik went into the archives and retrieved samples of tissue from osteosarcoma patients who had been treated at KU Hospital. Placed under a microscope, the tissue samples indicated that bone tumors have the receptors necessary to bind with vitamin D.
In the second arm of the study, Rama Garimella, PhD, MS, MSc, a research assistant professor in the School of Health Professions' Department of Dietetics and Nutrition, along with her graduate students Lindsey Thompson and Shanshan Wang, investigated the effects of vitamin D on human osteosarcoma cell lines at the cellular and molecular levels. "Vitamin D has been well studied in other different types of cancers, like prostate, breast and colon cancers," says Garimella, the senior and corresponding author of the study. "The role of vitamin D in osteosarcoma is not clearly defined."
The results of pilot studies from Garimella's lab suggest that vitamin D induces differentiation and apoptosis, or cell death, in human osteosarcoma cell lines. In other words, vitamin D promoted the growth of normal bone cells by expressing bone markers. "It remains to be tested whether vitamin D exerts a similar differentiation-inducing effect in vivo," Garimella says.
Other co-authors of the study include Jakica Tancabelic, MD; David Pinson, DVM, PhD; H. Clarke Anderson, MD; and John Keighley, PhD.
The results suggest that vitamin D could become another tool in the treatment of osteosarcoma. Patients with low levels of vitamin D would potentially receive supplements during chemotherapy in an effort try to increase the number of osteosarcoma cells that turn into normal bone. "We're not saying that vitamin D is going to be the thing that cures osteosarcoma," Templeton says. "We wouldn't use it as a single agent, the only drug that you give, but rather would add it into current treatment regimens."
More tests are needed before doctors begin recommending vitamin D for their osteosarcoma patients. "All we know is what it does in a petri dish," Templeton says. The next step is to introduce vitamin D to osteosarcoma cells in mice or dogs. (Bone tumors are fairly common in large breed dogs.) In any event, Templeton is encouraged by the discovery. The chemotherapy that is used now to treat osteosarcoma, she says, is effective but also poses significant side effects to the heart, kidneys or bone, depending on the regimen.
"The beauty of vitamin D is that at relatively normal doses it's not going to have a long-term side effect like that," she says. "When you're dealing with growing kids, that's something you really need to be concerned about. Yes, you want to try to eradicate their cancer, but you also, if they do survive, want to understand what those drugs and that treatment is doing 20 and 30 and 40 years after they've been treated."
Templeton also notes that vitamin D is inexpensive, an important consideration at a time of concern about health care spending.
Templeton says the primary objective of the research into vitamin D is to lower the mortality rate of osteosarcoma patients, many of whom are not old enough to drive when they first come to see her. "There's nothing quite as gratifying as treating a child or teenager with this condition and have them coming back when they've graduated high school or graduated college so you know they've made it," she says.