Bone cancer pain: the effects of the bisphosphonate alendronate on pain, skeletal remodeling, tumor growth and tumor necrosis.
Patients with metastatic breast, lung or prostate cancer frequently have significant bone cancer pain. In the present report we address, in a single in vivo mouse model, the effects the bisphosphonate alendronate has on bone cancer pain, bone remodeling and tumor growth and necrosis. Following injection and confinement of green fluorescent protein-transfected murine osteolytic tumor cells into the marrow space of the femur of male C3H/HeJ mice, alendronate was administered chronically from the time the tumor was established until the bone cancer pain became severe. Alendronate therapy reduced ongoing and movement-evoked bone cancer pain, bone destruction and the destruction of sensory nerve fibers that innervate the bone. Whereas, alendronate treatment did not change viable tumor burden, both tumor growth and tumor necrosis increased. These data emphasize that it is essential to utilize a model where pain, skeletal remodeling and tumor growth can be simultaneously assessed, as each of these can significantly impact patient quality of life and survival.
Department of Preventive Sciences, University of Minnesota, 515 Delaware Street, Minneapolis, MN 55455, USA.
Molly A
MA
Sevcik
Nancy M
NM
Luger
David B
DB
Mach
Mary Ann C
MA
Sabino
Christopher M
CM
Peters
Joseph R
JR
Ghilardi
Matthew J
MJ
Schwei
Heidi
H
Röhrich
Carmen
C
De Felipe
Michael A
MA
Kuskowski
Patrick W
PW
Mantyh
D051700:Activating Transcription Factor 3; D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal; D014408:Biomarkers, Tumor; D001859:Bone Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009336:Necrosis; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D010014:Osteolysis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D012509:Sarcoma / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism
D051700:Activating Transcription Factor 3; D014408:Biomarkers, Tumor; D014157:Transcription Factors; D019386:Alendronate