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.
Bibliographical noteFunding Information:
We are grateful to John Obenchain (Merck & Co., Rahway, NJ, USA) for the gift of the alendronate used in this study. This work was supported by the National Institute of Health, grants from the National Institute of Neurological Disorders and Stroke (NS23970), the National Institute for Drug Abuse (DA11986) and a Merit Review from the Veterans Administration. This work was also supported by the Individual Predoctoral Dental Scientist Fellowship (1F30-DE01471-01A1) and the NIDCR Dentist Scientist Award (5 K16 DE00270-12).
Copyright 2012 Elsevier B.V., All rights reserved.