Teriparatide Does Not Exacerbate Bone Metastases in Breast Cancer Bone Metastasis Model

Abstract

Background/aim: Breast cancer frequently metastasizes to bone, and chemotherapy and hormone therapy can increase osteoporosis risk. Teriparatide (TPTD), an osteoporosis treatment that promotes bone formation, is contraindicated in patients with bone metastases due to concerns about osteosarcoma in animal studies. However, its effects on metastatic bone tumors remain unclear. This study aimed to evaluate TPTD's effects on breast cancer bone metastases using a mouse model.

Materials and methods: C57BL/6 mice were injected with E0771 breast cancer cells to establish bone metastasis and breast cancer models. Mice were assigned to the vehicle-treated group (control) or to the TPTD-treated group (80 μg/kg, subcutaneously three times weekly). Tumor weight, volume, bone destruction, pathological fractures, distant metastasis, tumor proliferation (Ki-67, BrdU), and bone microstructure were assessed at 4 and 6 weeks.

Results: In both models, no significant differences in tumor weight or volume were observed between the TPTD and control groups. In the bone metastasis model, bone destruction and pathological fractures were not significantly different. No distant metastasis was observed and there were no significant differences in the percentages of Ki-67-positive and BrdU-positive cells in both models. In the bone microstructure analysis at 6 weeks post-injection, bone volume/tissue volume and trabecular thickness increased in the bone metastasis model in the TPTD group (p=0.02 and p<0.01, respectively), and trabecular separation decreased in the TPTD group (p=0.01).

Conclusion: TPTD did not cause tumor growth, pathological fractures, or bone destruction in our in vivo models, indicating that it may be safe for use in breast cancer.

Keywords: Bone metastasis; breast cancer; breast cancer bone metastasis model; breast cancer mouse model; teriparatide.

Figure 1

The figure depicts the experimental procedure of the study. We developed bone metastasis and breast cancer models in C56/BL/6 mice (n=40 in each model). Two weeks after tumor cell administration, mice in each model were treated with vehicle (control group; n=20) or with TPTD (n=20) and were euthanized at week 4 and week 6. TPTD, Teriparatide.

Figure 2

Micro-CT 3D image of the right femur in the bone metastasis model at 6 weeks. Representative images of the femur of mice in the TPTD (A) and control (B) groups show that similar bone destruction was observed in both groups. TPTD, Teriparatide; CT, computed tomography.

Figure 3

Ki-67 expression in tumor tissues at week 4 after treatment. Representative histological images show Ki-67 expression in tumor tissues from mice with bone metastasis treated with TPTD (A) or vehicle (B), as well as from mice with breast cancer in the TPTD (C) and control (D) groups (×400 magnification). TPTD, Teriparatide.

Figure 4

BrdU staining in tumor tissues at week 4 after treatment. Representative histological images show BrdU-positive cells in tumor tissues of TPTD (A) and control (B) mice of the bone metastasis model and of TPTD (C) and control (D) mice of the breast cancer model (×400 magnification). TPTD, Teriparatide.