Effects of Whole-Body Vibration on Breast Cancer Bone Metastasis and Vascularization in Mice

We evaluated whether whole body vibration (WBV) prevented bone loss induced by breast cancer (BC) metastasis and the involvement of bone marrow vasculature. One day after orthotopic transplantation of mammary 4T1 tumor cells, 8-week-old BALB/c mice were subjected to 0.3 g/90 Hz vertical vibration for 20 min/day for 5 days/week (BC-WBV) or sham-handled (BC-Sham) over 3 weeks. Age-matched intact mice (Intact) were also sham-handled. Both tibiae were harvested from BC-WBV (n = 7), BC-Sham (n = 9), and Intact (n = 5) mice for bone structure imaging by synchrotron radiation-based computed tomography (SRCT) and hematoxylin and eosin staining, whereas right tibiae were harvested from other BC-WBV and BC-Sham (n = 6 each) mice for vascular imaging by SRCT. Tumor cells were similarly widespread in the marrow in BC-WBV and BC-Sham mice. In BC-Sham mice, cortical bone volume, trabecular volume fraction, trabecular thickness, trabecular number density, and bone mineral density were smaller, and marrow volume and trabecular separation were larger than in Intact mice. However, although trabecular thickness was smaller in BC-WBV than Intact mice, the others did not differ between the two groups. Serum osteocalcin tended to be higher in BC-WBV than BC-Sham mice. Compared with BC-Sham mice, BC-WBV mice had a smaller vessel diameter, a trend of a larger vessel number density, and smaller vessel diameter heterogeneity. In conclusion, WBV mitigates bone loss in BC bone metastasis, which may be partly due to increased bone anabolism. The alteration of marrow vasculature appears to be favorable for anti-tumor drug delivery. Further studies are needed to clarify the multiple actions of WBV on bone, tumor, and marrow vasculature and how they contribute to bone protection in BC metastasis.

This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use (https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms), but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s00223-022-01009-4