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

Prisca Honore, Nancy M. Luger, Mary Ann C. Sabino, Matthew J. Schwei, Scott D. Rogers, David B. Mach, Patrick F. O'Keefe, Margaret L. Ramnaraine, Denis R. Clohisy, Patrick W. Mantyh

Research output: Contribution to journalArticlepeer-review

422 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)521-528
Number of pages8
JournalNature Medicine
Volume6
Issue number5
DOIs
StatePublished - May 2000

Bibliographical note

Funding Information:
Acknowledgments 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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