Abstract | BACKGROUND: 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.
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Authors | Martine P Roudier, Steven D Bain, William C Dougall |
Journal | Clinical & experimental metastasis
(Clin Exp Metastasis)
Vol. 23
Issue 3-4
Pg. 167-75
( 2006)
ISSN: 0262-0898 [Print] Netherlands |
PMID | 16912914
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Osteoprotegerin
- RANK Ligand
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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
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