Pamidronate prevents the development of skeletal metastasis in nude mice transplanted with human breast cancer cells by reducing tumor burden within bone.
Pamidronate is used routinely in the treatment of established bone metastasis. However, pamidronate has not yet been assessed in the prevention of osteolytic bone metastasis and its precise mechanism of action in this disorder remains to be established. In the present study, pamidronate or vehicle alone was administered subcutaneously to nude mice either simultaneously or as post intracardiac injection of the human breast cancer MDA-MB-231 cells. Radiographs were used first to assess the presence of osteolytic bone metastases. Kaplan-Meier analysis demonstrated that animals treated with pamidronate early, but not late, showed a slower progression of bone metastases and hind limb paralysis than did vehicle-treated animals. Mann-Whitney analysis showed that only 44.4% of mice treated with pamidronate at the time of tumor cell inoculation developed bone metastases as compared to over 80% (p<0.05) of mice receiving vehicle alone. We then analyzed the number of bone lesions and their volume at time of sacrifice by bone histomorphometry. In contrast to X-ray analysis, morphometric analysis indicates that the number of lesions within bone was similar in pamidronate and vehicle-treated mice but that the lesions were significantly smaller and therefore, often not visible on radiographs. These results demonstrate that pamidronate is effective in reducing tumor burden in breast cancer metastatic to bone and is most effective as a preventative agent when administered closest in time to implantation of tumor cells. Our data also suggest that pamidronate acts mainly by inhibiting the growth of established bone metastatic lesions but has no effect on the metastatic spread itself.
El-Abdaimi
Khadija
K
Department of Medicine, Calcium Research Laboratory, McGill University and Royal Victoria Hospital, Montreal, Quebec H3A 1A1, Canada.
Ste-Marie
Louis-Georges
LG
Papavasiliou
Vasilios
V
Dion
Nathalie
N
Cardinal
Patrice-Etienne
PE
Huang
Dao
D
Kremer
Richard
R
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000473:pathology*; D001842:Bone and Bones / Q000473:pathology*; D002118:Calcium / Q000097:blood; D045744:Cell Line, Tumor; D003404:Creatinine / Q000097:blood; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007668:Kidney / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D000077268:Pamidronate; D013997:Time Factors; D014965:X-Rays
D000970:Antineoplastic Agents; D004164:Diphosphonates; D003404:Creatinine; D000077268:Pamidronate; D002118:Calcium