Nature Medicine
6, 521 - 528 (2000)
doi:10.1038/74999
Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal
pain and pain-related neurochemical reorganization of the spinal cordPrisca Honore1, Nancy M. Luger1, Mary Ann C. Sabino1, Matthew J. Schwei1, Scott D. Rogers1, David B. Mach1, Patrick F. O'keefe2, Margaret L. Ramnaraine2, Denis R. Clohisy2
& Patrick W. Mantyh11
Neurosystems Center and Departments of Preventive Sciences,
Psychiatry, Neuroscience, and Cancer Center, University of Minnesota,
Minneapolis, Minnesota 55455 and VA Medical
Center, Minneapolis, Minnesota 55417,
USA
2
Department of Orthopedic Surgery and Cancer Center,
University of Minnesota, Minneapolis, Minnesota
55455, USA
Correspondence should be addressed to Patrick W. Mantyh manty001@ tc.umn.edu or Denis R. Clohisy clohi001@ tc.umn.eduBone 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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