Causes, management of osteosarcoma bone pain

Osteosarcoma is a common cancer to see in larger, middle-aged to older dogs. One of the challenges in treating these patients is pain management. Amputation effectively relieves bone pain and is the standard of care for patients, but may not be an option for all dogs.

Poor candidates for amputation include patients with significant orthopedic or neurologic disease, pre-existing metastatic disease or owner preference. The focus of treatment for this subset of dogs becomes effective pain management.

Mechanism of bone pain

The cause of bone pain is two-fold: activation of osteoclasts by tumor cells and activation of nocioceptors due to prostaglandin and cytokine production. The dysregulated osteoclastic activity leads to bone resorption and malignant osteolysis. Uncontrolled osteolysis can lead to hypercalcemia, pathologic fractures and moderate to severe pain. For effective pain management, both of these causes need to be addressed.

Current therapies

Options available for the treatment of bone pain include NSAIDs, steroids, narcotics and palliative radiation therapy. NSAIDs and narcotics can be helpful in reducing pain secondary to increased prostaglandins and cytokine levels, but do not affect osteoclastic bone destruction.

It is debatable whether chemotherapy by itself is capable of providing any degree of pain relief.

Palliative radiation therapy involves several larger doses of radiation weekly or bi-weekly.

Side effects are minimal, and in published studies 70 percent to 90 percent of dogs experienced pain relief an average of two to four months.

Immediate pain relief is attributed to a decrease in the release of chemical mediators such as prostaglandins, while later pain relief is felt to be secondary to recalcification and repair of osteolytic lesions. (Green EM, Adams, WM Forrest LJ. Four Fraction Palliative Radiotherapy for Osteosarcoma in 24 Dogs. J Am Anim Hosp Assoc 2002;38:445-451).

Pamidronate for osteosarcoma bone pain

It is logical to assume that by decreasing osteoclastic bone destruction, patients will experience significant pain relief and show an increase in bone density.

Bisphosphonates, in particular the aminobisphosphonates, are a class of drugs capable of decreasing bone resorption. The most popular use of these drugs in humans has been in the prevention of osteoporosis, but several of the drugs have been used for the relief of bone pain, delaying the progression of bone lesions and controlling hypercalcemia.

Pamidronate has been safely administered to healthy, skeletally mature dogs with minimal side effects. In a recent study, pamidronate was administered intravenously to 43 dogs with appendicular osteosarcoma. Dogs were given 1-2 mg/kg of pamidronate over two hours. Responses were assessed using a clinical pain-score questionnaire (Table 1), serial limb radiographs, bone-density measurements and urinary N-telopeptide (NTx) excretion.

Table 1 Subjective clinical pain-score questionnaire

Urinary NTx is a marker of bone resorption, which decreases with effective anti-resorptive therapy. It was found that 28 percent (12/43) experienced significant pain relief based on the pain scores for a median of 231 days. Patients with decreases in the pain score were also those that showed a significant increase in bone density. Urinary NTx decreased in all treated patients regardless of response, although it increased significantly in the responder group at the time of pain recurrence. (Fan TM, Lorimier LP, Charney SC et al: Single-Agent Pamidronate for Palliative Therapy of Canine Appendicular Osteosarcoma Bone Pain. J Vet Intern Med 2007;21:431-439).

Summary

Pamidronate provides a novel method of pain relief in dogs with osteosarcoma. It can be safely combined with other methods of pain relief such as radiation therapy for more effective pain control. There may be other potential uses for this drug as well, including the treatment of other cancers that create bone osteolysis and hypercalcemia of malignancy.

Dr. Cronin earned her DVM degree from Cornell University in 1990. She completed an internship at the Animal Medical Center in New York and a medical oncology residency at North Carolina State University. She is a diplomate of the American College of Veterinary Internal Medicine in the specialty of oncology. After completing her residency, she was a lecturer at the University of Pennsylvania Veterinary Teaching Hospital and a medical oncologist at Angell Memorial Animal Hospital in Boston. In 2001, she co-founded the New England Veterinary Oncology Group in Waltham, Mass.