Effect of Zoledronic Acid Administration Timing on Metastatic Bone Tumors.

Abstract

Background/aim: Breast cancer frequently metastasizes to the bone, reducing quality of life and survival. Zoledronic acid (ZA), is used to treat bone metastasis; however, differences in efficacy depending on the timing of administration are not clear. This study investigated the effects of different timing of ZA administration in a mouse model of breast cancer bone metastasis.

Materials and methods: E0771 cells (1.0×10⁵ cells/10 μl) were injected into the femur of C57BL/6 mice to create a local bone metastasis model. The groups that started ZA administration one week before, at the same time as, one week after, and two weeks after tumor-cell administration were designated as the -1w, 0w, 1w, and 2w groups, respectively. A fifth group that did not receive ZA treatment was created as a control. ZA was administered at a dose of 100 μg/kg, and the same dose was administered once a week from the start of administration. The animals were sacrificed two and five weeks after tumor-cell administration. We evaluated body weight at the time of tumor-cell administration and sacrifice, and after sacrifice, the weight of the affected thigh, tumor volume, and bone destruction rate were determined using micro-computed tomography. Tumor necrosis and tumor growth were measured using histological immunostaining.

Results: Five weeks after tumor-cell administration, bone destruction rate was significantly lower in all groups compared to the control group (p<0.05). Additionally, the -1w group exhibited a significantly lower bone destruction rate than 1w and 2w groups (p<0.05). There were no significant differences in tumor necrosis, but tumor growth was significantly lower in the -1w and 0w groups (p<0.05).

Conclusion: The earlier ZA was administered, the more strongly it suppressed bone destruction and tumor cell proliferation.