Osteosarcoma in Dogs (OSA)
Osteosarcoma accounts for only approximately 5% of all canine tumors, but is by far the most common bone tumor of the dog. It is a malignant tumor of the bone and can develop in any bone, but most often occurs in bones bordering the shoulder, wrist and knee. Osteosarcoma of the limbs is called appendicular osteosarcoma and accounts for 75-85% of the cases of bone cancer. However, these tumors can also affect the axial skeleton (cranium, spinal column, ribs).
Osteosarcoma develops deep within the bone and becomes progressively more painful as it grows outward and thebone is destroyed from the inside out. Lameness may occur suddenly or start intermittently and progress over several weeks. Obvious swelling becomes evident as the tumor grows and normal bone is replaced by tumorous bone.
Tumorous bone is not as strong as a healthy bone and can break with minor injury. This type of broken bone is called a pathologic fracture. Pathologic fractures will not heal, therefore it is critical to diagnose and start treatment for osteosarcoma before this occurs.
Osteosarcoma usually occurs in middle aged or elderly large and giant breed dogs but can occur in a dog of any age with larger breeds tending to develop tumors at younger ages.
Highly aggressive and metastatic in nature, over 90% of all clinically significant osteosarcomas have already micrometastasized by the time of diagnosis. Most metastasis happens via hematogenous spread to the lungs and other bones, but lymph node metastases have been reported.
The specific cause of osteosarcoma is not known. However, because osteosarcoma tumors are frequently found near growth plates, it is speculated that factors that affect growth rates, such as diets that promote rapid growth in puppies, appear to influence risk.
Osteosarcomas tend to anchor themselves in areas of increased bone remolding, 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.”
Ionizing radiation, chemical carcinogens, and foreign bodies (including metal implants, such as internal fixators, bullets, and bone transplants contribute to the development of osteosarcoma. In addition, there have been correlations with genetic predisposition to tumor development in certain family lines. Dogs with osteosarcoma have been found to have aberrations of the p53 tumor suppressor gene. In laboratory animals, both DNA viruses (polyomavirus and SV-40 virus) and RNA viruses (type C retroviruses) have been found to induce osteosarcoma.
Research was performed in 2002 to determine if spaying or neutering a dog increased the risk of developing bone cancer. Experimental and clinical evidence suggests that endogenous sex hormones influence bone sarcoma genesis but the hypothesis had not been adequately tested in an appropriate animal model. A historical study was conducted of Rottweiler dogs because they frequently undergo elective gonadectomy and spontaneously develop appendicular bone sarcomas, which mimic the biological behavior of the osteosarcomas that affect children and
In summary, this study found that male and female Rottweilers with the shortest lifetime gonadal exposure had the highest risk for bone sarcoma. Dogs that underwent early elective gonadectomy had a one in four lifetime risk of bone sarcoma development compared with a significantly reduced risk among dogs that were sexually intact throughout their lifetime. Although it remains unclear how endogenous gonadal hormones influence bone sarcoma development, the work provides the framework for selecting a target population for bone sarcoma prevention studies. To read the complete study, please click here: http://cebp.aacrjournals.org/cgi/content/full/11/11/1434
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 risk of bone cancer is slightly higher in males than females. In addition, it is 65% higher for castrated males and 34% higher for spayed females. The probability of developing bone cancer was higher both in females spayed at less than one year of age, as well as males castrated when they were less than a year old, compared with animals that were not spayed or neutered. Apparently, sex hormones are somewhat protective against the disease.