Clinical & Experimental Metastasis

, Volume 23, Issue 3–4, pp 167–175

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

  • Martine P. Roudier
  • Steven D. Bain
  • William C. Dougall
ORIGINAL PAPER

DOI: 10.1007/s10585-006-9026-x

Cite this article as:
Roudier, M.P., Bain, S.D. & Dougall, W.C. Clin Exp Metastasis (2006) 23: 167. doi:10.1007/s10585-006-9026-x

Abstract

Background

This study investigated the effects of the receptor activator for nuclear factor κB 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.

Keywords

Bone neoplasms Mammary neoplasms Animal Osteoprotegerin Pain RANK ligand Rats 

Abbreviations

ANOVA

Analysis of variance

BMD

Bone mineral density

DXA

Dual X-ray absorptiometry

GFAP

Glial fibrillary acidic protein

MicroCT

Micro-computed tomography

MRMT-1

Rat mammary tumor cell line

OPG

Osteoprotegerin

RANK

Receptor activator for nuclear factor κB

RANKL

Receptor activator for nuclear factor κB ligand

sTRAP5b

Tartrate-resistant acid phosphatase form 5b

Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • Martine P. Roudier
    • 1
    • 3
  • Steven D. Bain
    • 1
  • William C. Dougall
    • 2
  1. 1.SkeleTech, Inc.BothellUSA
  2. 2.Department of Cancer BiologyAmgen WashingtonSeattleUSA
  3. 3.Department of PathologyAmgen WashingtonSeattleUSA

Personalised recommendations