Cancer-induced bone loss and associated pain-related behavior is reduced by risedronate but not its phosphonocarboxylate analog NE-10790

Research output: Contribution to journalJournal articleResearchpeer-review

Andreas Hald, Rikke Rie Hansen, Mette W Thomsen, Ming Ding, Peter I Croucher, Orla Gallagher, Frank H Ebetino, Moustapha Kassem, Anne-Marie Heegaard

Prostate, breast and lung cancers readily develop bone metastases which lead to fractures, hypercalcemia and pain. Malignant growth in the bones depends on osteoclast-mediated bone resorption and in this regard bisphosphonate compounds, which have high-bone affinity and inhibit osteoclast activity, have been found to alleviate bone cancer symptoms. In this study, the bisphosphonate risedronate and its phosphonocarboxylate derivative NE-10790 was tested in a murine bone cancer pain model. Risedronate decreased bone cancer-related bone destruction and pain-related behavior and decreased the spinal expression of glial fibrillary acidic protein, whereas NE-10790 had no effect on these parameters. Furthermore, risedronate but not NE-10790 induced dose-dependent toxicity in NCTC-2472 cells in vitro. Furthermore, the direct toxic effect of risedronate on tumor cells observed in vitro opens the possibility that a direct toxic effect on tumor cells may also be present in vivo and be related to the efficacy of bisphosphonate compounds. In conclusion, these results suggest that risedronate treatment may lead to an increased life quality, in patient suffering from bone cancer, in terms of decreased osteolysis and pain, and merits further study.
Original languageEnglish
JournalInternational Journal of Cancer
Volume125
Issue number5
Pages (from-to)1177-85
Number of pages8
ISSN0020-7136
DOIs
Publication statusPublished - 2009

Bibliographical note

Keywords: Acid Phosphatase; Animals; Behavior, Animal; Bone Density Conservation Agents; Bone Neoplasms; Bone Resorption; Cell Proliferation; Cells, Cultured; Diphosphonates; Etidronic Acid; Fibroblasts; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Isoenzymes; Male; Mice; Mice, Nude; Pain; Pyridines; Xenograft Model Antitumor Assays

ID: 17085788