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Cancer‐induced bone loss and associated pain‐related behavior is reduced by risedronate but not its phosphonocarboxylate analog NE‐10790
Author(s) -
Hald Andreas,
Hansen Rikke R.,
Thomsen Mette W.,
Ding Ming,
Croucher Peter I.,
Gallagher Orla,
Ebetino Frank H.,
Kassem Moustapha,
Heegaard AnneMarie
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24436
Subject(s) - bisphosphonate , medicine , bone resorption , osteolysis , osteoclast , bone pain , in vivo , bone cancer , cancer , bone metastasis , osteoporosis , cancer research , prostate cancer , endocrinology , surgery , biology , receptor , microbiology and biotechnology
Abstract 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. © 2009 UICC