Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord.
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.
Honore
P
P
Neurosystems Center and Departments of Preventive Sciences, Psychiatry, Neuroscience, and Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Luger
N M
NM
Sabino
M A
MA
Schwei
M J
MJ
Rogers
S D
SD
Mach
D B
DB
O'keefe
P F
PF
Ramnaraine
M L
ML
Clohisy
D R
DR
Mantyh
P W
PW
D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D018488:Bone Demineralization, Pathologic / Q000188:drug therapy*; D006023:Glycoproteins / Q000627:therapeutic use*; D006614:Hindlimb / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010010:Osteoclasts / Q000187:drug effects; D053244:Osteoprotegerin; D012516:Osteosarcoma / Q000150:complications*; D010146:Pain / Q000188:drug therapy*; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D012513:Sarcoma, Experimental / Q000150:complications; D013116:Spinal Cord / Q000187:drug effects*
D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; C506031:Tnfrsf11b protein, mouse