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Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord

Nature Medicine volume 6, pages 521–528 (2000)Cite this article

An Erratum to this article was published on 01 July 2000

Abstract

Bone cancer pain is common among cancer patients and can have a devastating effect on their quality of life. A chief problem in designing new therapies for bone cancer pain is that it is unclear what mechanisms drive this distinct pain condition. Here we show that osteoprotegerin, a secreted ‘decoy’ receptor that inhibits osteoclast activity, also blocks behaviors indicative of pain in mice with bone cancer. A substantial part of the actions of osteoprotegerin seems to result from inhibition of tumor-induced bone destruction that in turn inhibits the neurochemical changes in the spinal cord that are thought to be involved in the generation and maintenance of cancer pain. These results demonstrate that excessive tumor-induced bone destruction is involved in the generation of bone cancer pain and that osteoprotegerin may provide an effective treatment for this common human condition.

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Figure 1: OPG abolishes sarcoma-induced bone destruction.
Figure 2: OPG reduces the number of osteoclasts and bone destruction in mice injected with sarcoma cells.
Figure 3: Inhibitory effects of OPG on sarcoma-induced bone destruction.
Figure 4: OPG blocks both spontaneous and evoked pain behaviors seen in sarcoma-injected mice.
Figure 5: Osteoprotegerin blocks astrocyte hypertrophy seen in the spinal cord 17 d after sarcoma injection in mice.

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Acknowledgements

We thank D. Lacey at Amgen (Thousand Oaks, California) for comments on the manuscript and J. Schmidt for technical assistance. This work was supported by a Merit Review from the Veterans Administration, National Institutes of Health grants from the National Institute of Neurological Disorders and Stroke (NS23970) and the National Institute for Drug Abuse (11986), National Institute of Dental and Craniofacial Research training grant DEO7288, National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR43595), the Roby C. Thompson, Jr. Endowment in Musculoskeletal Oncology, a Dentist Scientist Award (DSA) DE00270, and a grant from the University of Minnesota Academic Health Center Strategic Initiative.

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Authors and Affiliations

  1. Neurosystems Center and Departments of Preventive Sciences Psychiatry, Neuroscience, and Cancer Center, University of Minnesota, Minneapolis, 55455, Minnesota

    Prisca Honore, Nancy M. Luger, Mary Ann C. Sabino, Matthew J. Schwei, Scott D. Rogers, David B. Mach & Patrick W. Mantyh

  2. VA Medical Center, Minneapolis, 55417, Minnesota, USA

    Prisca Honore, Nancy M. Luger, Mary Ann C. Sabino, Matthew J. Schwei, Scott D. Rogers, David B. Mach & Patrick W. Mantyh

  3. Department of Orthopedic Surgery and Cancer Center University of Minnesota, Minneapolis, 55455, Minnesota, USA

    Patrick F. O'keefe, Margaret L. Ramnaraine & Denis R. Clohisy

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Correspondence to Denis R. Clohisy or Patrick W. Mantyh.

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Honore, P., Luger, N., Sabino, M. et al. Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord. Nat Med 6, 521–528 (2000). https://doi.org/10.1038/74999

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