HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Effects of the RANKL inhibitor, osteoprotegerin, on the pain and histopathology of bone cancer in rats.

AbstractBACKGROUND:
This study investigated the effects of the receptor activator for nuclear factor kappaB ligand (RANKL) inhibitor, osteoprotegerin (OPG), on tumor-induced allodynia, osteolysis, and bone histology in the mammary tumor (MRMT-1) rat model for bone cancer pain.
METHODS:
Rats (n = 8/group) were inoculated with MRMT-1 or culture medium in the proximal right tibia, injected with OPG or vehicle subcutaneously 2-3 times weekly, evaluated for mechanical allodynia with von Frey paw stimulation, and euthanized on Day 20 for necropsy. Three groups were evaluated starting on Day 5 and received the following interventions beginning on Day 1: tumor and OPG, tumor and vehicle, or culture medium and vehicle. Three additional groups received the same interventions but were evaluated starting on Day 3. A seventh group started OPG on Day 8 after tumor inoculation.
RESULTS:
Starting OPG on Day 1 reduced allodynia significantly compared with vehicle injections; pain relief was observed within 5-6 days after tumor inoculation and lasted throughout follow-up. Starting OPG on Day 8 did not reverse allodynia significantly compared with the tumor control group. Regardless of treatment start time, OPG treatment reduced osteoclast number and tartrate-resistant acid phosphatase levels, increased bone mineral density, preserved normal bone volume and integrity on micro-computed tomography, reduced relative tumor volume in the bone, and reduced staining for glial fibrillary acidic protein in the spinal cord.
CONCLUSIONS:
RANKL inhibition with OPG reduced bone resorption and bone pain in rats with malignant bone disease; further study is warranted to determine if RANKL inhibition has similar benefits in humans.
AuthorsMartine P Roudier, Steven D Bain, William C Dougall
JournalClinical & experimental metastasis (Clin Exp Metastasis) Vol. 23 Issue 3-4 Pg. 167-75 ( 2006) ISSN: 0262-0898 [Print] Netherlands
PMID16912914 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Osteoprotegerin
  • RANK Ligand
Topics
  • Animals
  • Bone Density (drug effects)
  • Bone Neoplasms (drug therapy, secondary)
  • Bone Resorption (drug therapy)
  • Female
  • Mammary Neoplasms, Experimental (pathology)
  • Neoplasm Transplantation
  • Osteoprotegerin (administration & dosage, pharmacology)
  • Pain (drug therapy)
  • RANK Ligand (antagonists & inhibitors)
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: