Osteosarcoma is both locally invasive and metastatic, developing deep within the bone of the limbs (it can develop in any bone but the limbs are the most common areas affected). Seventy-five percent of osteosarcomas occur in the long bones, followed by 23% that arise in the flat bones. As the tumor progresses outward, the bone is destroyed from the inside out; then cancer cells spread throughout the body. Obvious swelling becomes evident as the tumor grows and normal bone is replaced by tumorous bone. (Tumorous bone is not as strong as normal bone and can break with a minor injury. This type of broken bone is called a “pathologic fracture.”) By the time clinical symptoms become evident, the tumor is advanced.

Any sudden onset of lameness over a two to five day period or localized swelling around the site of the lesion should be investigated. The first step in evaluating a persistent lameness is radiography (x-rays), which is usually all that is needed for diagnosis. If there is any question about the lesion on the radiographs, a bone biopsy provides conclusive results. Chest radiographs should be performed in dogs diagnosed with osteosarcoma, since 90% of afflicted dogs have pulmonary metastasis at the time of diagnosis, although lung nodules may not yet be visible.

This is a horrendous form of canine cancer, very painful with a poor prognosis. Most dogs eventually die of metastasis to the lungs or other organs. Radiation will alleviate some of the pain, but the treatment offering the longest survival time is amputation of the involved limb, followed immediately with aggressive chemotherapy. (Unlike with humans, dogs do not suffer many side effects from chemotherapeutic drugs.) In a study at Kansas State University, cisplastin and doxorubicin were used in combination within 24 hours after amputation, over a 21-day cycle for 4 doses. The median disease-free survival rate for the study dogs was 15 and 18 months, with one dog surviving for 24 months and another for 75 months. The average survival time without aggressive treatment is less than nine months.
 

Not all dogs are candidates for amputation. Limb sparing, also known as "limb salvage,” is an alternative surgical procedure that can preserve the limb in dogs with arthritis or other orthopedic problems. The goal in limb sparing is to remove the diseased bone and surrounding tissues while still preserving the function of the remaining limb. The piece of diseased bone removed is replaced by a combination of healthy bone from a donor and bone graft from other parts of the patient's body. While much of the leg's function is preserved, there is decreased range of motion in the treated limb, resulting in limited activity for the dog. Limb sparing is performed in conjunction with chemotherapy (and in some instances, radiation therapy as well). At this time, the only good results are in dogs with tumors of the distal radius (the "wrist" joint). More than three-quarters of these patients return to near normal function. Radiation therapy can be effective in destroying neoplastic cells at the primary tumor site, and chemotherapy may be employed to prevent or delay metastasis. Carboplastin, cisplastin and doxorubicin, are part of a typical, after surgery osteosarcoma chemotherapy protocol.

In the May 2002 article,” Gene Therapy Treatment for Canine Cancer,” by Karen Earles (Dog & Kennel Magazine), immunotherapy, which activates the immune system to combat cancer cells, is providing a ray of hope in treatment of osteosarcoma. Robyn Elmslie, D.V.M., veterinary oncologist at the Veterinary Referral Center (VRC) of Colorado, and her husband Steven Dow, D.V.M., Ph.D., an immunologist at the National Jewish Medical Research Center in Denver, have been evaluating gene therapy for the treatment of cancer. “The gene interleuken 2 showed promising results. "Interleuken 2 is a normal gene found in all species," says Elmslie. "It plays a role in regulating the immune response. What we want to do is develop a stronger immune response. It's the immune system that does the tumor killing, not the actual product that we are providing. We're giving the tool that will hopefully help the body's immune system do its work. This form of immunotherapy involves combining interleuken 2 with a fatty acid called a lipid. It is given intravenously to dogs diagnosed with osteosarcoma. The gene combined with the lipid is able to target the lung tissues. "In earlier pre-clinical studies with mice, we have observed a marked immune stimulation after intravenous administration of lipid-DNA complexes, both systematically and in the lungs," says Dow.

The intravenous therapy has had a significant effect on Brandy, a 12-year-old yellow Labrador retriever. After 12 weeks, the tumors in her lungs were notably smaller than they had been six weeks earlier. Brandy has been receiving gene therapy for more than a year, and the lung tumors are extremely small. “Elmslie's and Dow's study, "Intravenous Gene Therapy for Canine Pulmonary Metastatic Cancer," is currently being funded by a foundation grant and covers the study for osteosarcoma only. The Veterinary Referral Center is involved with similar studies involving other forms of cancer, such as melanoma, which are being funded by other organizations, says Earles. “In order to be eligible for the study, a dog with osteosarcoma must have the primary tumor removed and undergo chemotherapy.”

On December 4, 2001, MSNBC reporter, Charlene Laino, described another promising new approach to treating osteosarcoma, which is under investigation at the University of Washington in Seattle. Extracted from the wormwood plant, the compound seeks out and destroys breast cancer cells while leaving healthy cells intact. Artemisinin, from the plant Artemesia annua L, commonly known as wormwood, has been used by Chinese practitioners for thousands of years, according to Laino’s report. “In laboratory experiments, the compound killed within 16 hours virtually all human breast cancer cells exposed to it in the test tube, reports Henry Lai, a bioengineering researcher at the University of Washington. Just as importantly, he says, nearly all of the normal cells exposed to it were still alive. And a dog with a type of bone cancer known as osteosarcoma so severe that it couldn’t walk across the room made a complete recovery within five days of receiving the treatment. X-rays showed the animal’s tumor “had basically disappeared,” says Lai, adding that he believes the dog is still alive two years later. Not only does [the drug] appear to be effective, but it’s very selective,” Lai says. It’s highly toxic to the cancer cells, but has a marginal impact on normal cells.

Please understand that the word “cure” is never used when discussing cancer. There are treatments that can extend the life of your dog, often with minimal discomfort. One such treatment is samarium 153, used in combination with the chemotherapeutic drug carboplastin.
 

The treatment itself consists of an injection of samarium-153, a radioactive isotope that targets rapidly growing bone cells. Samarium has a half-life of 48 hours. During the two-day period when the dog’s urine is highly radioactive, it is kept in isolation and monitored by trained medical personnel. After a bone scan, which allows for a more accurate evaluation of the bone and tumor, the dog is released back to the owner. During the following six weeks, the samarium remains within the tumor emitting beta rays that destroy the tumor cells. The danger occurs between the third and sixth week following the samarium treatment when the white cell count drops to a dangerously low level in response to the radiation exposure. Once the white blood cell counts returns to normal, the dog undergoes a series of treatments with the chemotherapeutic drug, carboplastin, to prevent metastasis.
 

According to Jeanne Young of Harbor UCLA, samarium has potential as a treatment in osteosarcoma. “After baseline laboratory studies, 21 dogs with biopsy proven bone sarcomas (17 osteo, two chondro, one chondro-osteo, one synovial) underwent intravenous treatment with Sm-153 EDTMP. Prior to SM 153 EDTMP, one dog had amputation of a limb, cisplastin therapy and external beam radiation, while another had surgery to debulk the tumor. Blood counts were obtained at intervals between one week and two months.
 

Results:  Three dogs with white blood cell (WBC) counts near zero developed sepsis and died within three weeks of treatment. One dog developed transient aplastic anemia at 13 weeks following cisplastin administration. Maximum WBD depression occurred at three to four weeks post Sm 153 EDTMP decreasing to critical levels below 0.5 x 10/mm, with platelets reaching nadir at three to four weeks. Post treatment survival time, excluding the animals that died from sepsis ranged from three months to one-year with an average survival of 20.2 weeks as compared to 8.7 weeks in prior series without Sm 153 EDTMP. Survival time increased to 19.9 weeks when cisplastin and/or surgery followed SM-153 EDTMP. With the exception of chondrosarcoma all dogs experienced pain relief. Follow up scans using Tc-99m methylene diphosphonate were performed after three months in five of 13 surviving dogs. Tumor uptake decreased in three of the five and remained stable in the other two following therapy. After high dose Sm-153 EDTMP pain palliation was apparent in all dogs with osteosarcoma. A small percentage of sarcomas may show long-term survival with Sm-153 EDTMP. Chondrosarcomas were unaffected. Myelosuppression was severe but transient in most.” (“Ethylenediaminetetramethylene Phosphate *SM-153 EDTMP) in the treatment of bone sarcomas, J.C. Young, F.S. Mishkin, May 1999)
 

Jeanne Young said it is important to treat with Sm-153 EDTMP again in six months and then annually thereafter. She believes external beam radiation--at least three treatments before treating with Sm-153 EDTMP-- increases the odds of survival. One of Jeanne’s patients, a Doberman pincher, was doing well after three years. Samarium is no longer offered at Harbor-UCLA, but a new study at the University of Missouri, headed by Dr. Carolyn Henry and funded by Morris Animal Foundation is underway.

The specific cause of osteosarcoma is not known.  Osteosarcomas tend to anchor themselves in areas of increased bone remodling, said Dr. Kim Cronin, oncologist at the University of Pennsylvania.

"Every time you have cell damage or increased turnover, the DNA is more likely to make a mistake when coding for new cells, which can lead to tumor formation."  So naturally, previous fractures and chronic bone infections are predisposing factors.  These tumors are most likely to occur in the limbs, particularly the forelimbs, which bear most of the body weight; other bones, such as the ribs and skull can also be affected."

A two-year study conducted by the National Toxicology Program  (NTP), using rats and mice, linked sodium fluoride in drinking water to osteosarcoma. The positive results of that study (in which malignancies in tissues other than bone were also observed), concurs with a host of data from tests showing fluoride's ability to cause mutations and data showing increases in osteosarcoma in young men in New Jersey, Washington and Iowa based on their drinking fluoridated water.

A sister chemical to lufenuron, which is a popular insect growth regulator used orally for flea control in dogs and cats,  is diflubenzuron. Two metabolites of diflubenzuron, para-chloroaniline (PCA) and 4-clorophenylurea  (CPU), increased the incidence of hemangiosarcoma and osteosarcoma in animal studies.  Lufenuron accumulates in fatty tissue.

A few studies with human osteosarcoma patients discovered low blood serum levels of zinc and selenium, but the relationship of these nutrients to the cancer are not yet understood. Evidence suggests that a predisposition to osteosarcoma runs in families. Studies with humans point to a connection with hereditary cancers. For example, the gene involved in familial retinoblastoma  appears to be a defective tumor inhibitor gene and is associated with other childhood tumors including osteosarcoma. We know that in humans and canines, tumor-suppressor genes like P53 produce proteins that inhibit tumor formation. If these genes are not present, or are damaged, the individual is more susceptible to tumor formation. The AKC’s Canine Health Foundation and breed clubs are sponsoring research to study osteosarcoma and tumor suppressor genes.

In July, 2005, a new look at some old research showed a definite link to fluoride in the water.  The research was done with young boys and warrants further study, but we cannot ignore any research that has proven links to this deadly cancer.  For more information on fluoride and osteosarcoma, please see the following websites:

http://www.health-report.co.uk/fluoriide_bone_cancer.htm
 

http://www.fluoridealert.org/health/cancer/osteosarcoma.html

Please visit the Canine Cancer Research Underway page.

If you lost a Leonberger to bone cancer or any other disease, please fill out a Cause of Death Registry Form and send it to the club.  It is the best way to understand health issues that take a toll on our Leonbergers.  You cannot solve a problem if you don't know it exists.

© 2001 by Barbara Bouyet: Excerpted from “Akita-Treasure of Japan-Volume II” by Barbara Bouyet, Magnum Publishing.