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

TY - JOUR

T1 - Cancer-induced bone loss and associated pain-related behavior is reduced by risedronate but not its phosphonocarboxylate analog NE-10790

AU - Hald, Andreas

AU - Hansen, Rikke Rie

AU - Thomsen, Mette W

AU - Ding, Ming

AU - Croucher, Peter I

AU - Gallagher, Orla

AU - Ebetino, Frank H

AU - Kassem, Moustapha

AU - Heegaard, Anne-Marie

N1 - 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

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1002/ijc.24436

DO - 10.1002/ijc.24436

M3 - Journal article

C2 - 19444917

SN - 0020-7136

VL - 125

SP - 1177

EP - 1185

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 5

ER -