Breast cancer has a propensity to metastasize to bone, leading to osteolytic bone destruction and, in some cases, abnormal new bone formation. Bone destruction in turn promotes the release of tumor growth factors and contributes to a vicious cycle of bone metastasis. In contrast, whole body vibration (WBV) downregulates the activity of osteoclastic bone resorption, possibly inhibiting bone metastasis. This therapeutic potential of WBV, however, could be counteracted by its proangiogenic effect, which may provide a more fertile environment for bone metastasis. Using a mouse model of breast cancer bone metastasis, we evaluated the effects of WBV on cancer-induced osteolytic/osteoblastic changes and vascularization. Female Balb/c 6-week-old mice received intratibial injection of 4T1 breast cancer cells (5×104 cells) in the right leg under anesthesia with isoflurane inhalation. The mice were randomly assigned to four groups (n=10 each): C2, W2, C4, and W4. Starting on the postoperative day 3, mice in W2 and W4 were exposed to WBV (0.3g at 90Hz) for 20min every day, and mice in C2 and C4 received a non-vibrated sham treatment. After 2 weeks of treatment, mice in C2 and W2 were thoracotomized under isoflurane anesthesia and perfused with zirconia-based vascular contrast-casting agent (Zr-CA) from the left ventricle. The animals were then euthanized by pentobarbital overdose (i.p.) and immersed in ice-cold water for solidifying Zr-CA. Mice in C4 and W4 were subjected to vascular casting similarly after 4 weeks of treatment. The proximal metaphyseal region was CT-scanned with synchrotron X-rays below and above the zirconia k-edge (SPring-8, Harima, Japan). Using k-edge subtraction, vascular and bone images were obtained separately (3.95-μm voxel resolution). Newly formed bone (new-B) were differentiated from pre-existent bone (pre-B) based on the degree of mineralization. A volume extending a distance of 2 mm distal to the growth plate defined the region for analysis. Values are means ± S.D., compared by Mann-Whitney U test. The volumes of pre-B and new-B were similar between W2 and C2 (pre-B: 0.38±0.12 vs. 0.40±0.14 mm3; new-B: 1.00±0.33 vs. 1.03±0.25 mm3). The pre-B volume decreased more in W4 than in C4 (0.10±0.06 vs. 0.17±0.08 mm3, p<0.05), while the new-B volume was similar between W4 and C4 (0.39±0.20 vs. 0.48±0.22 mm3). The vascular volume within 300 mm from pre-B regions was similar between W2 and C2 (0.0986±0.0157 and 0.0971±0.0302 mm3), which was lowered less in W4 than in C4 (0.0078±0.0025 vs. 0.0032±0.0067 mm3, p<0.05). The pooled data of W4 and C4 showed a negative correlation between the volumes of pre-B and its nearby vessels (p<0.05). These data suggest that WBV may reduce tumor vascular degeneration, thereby enhancing osteolytic bone destruction.