Tumor growth in bone is increased following G-CSF administration and is decreased by OC blockade in a second osteolytic model. (A) Mice were administered 200 μg/kg G-CSF (n = 18) or vehicle (n = 17) daily for 8 days or 200 μg/kg G-CSF daily for 8 days and 1 dose (0.75 μg) of zoledronic acid 1 day prior to tumor cell injection (n = 9). On the fifth day of G-CSF or vehicle administration, 10⁴ 4T1-GFP-FL tumor cells were injected into the right tibia. Tumor burden was assessed by bioluminescence imaging at days 3, 5, and 7 after tumor cell injection. G-CSF–administered mice demonstrated increased tumor burden compared with vehicle-administered mice, while G-CSF–administered mice given zoledronic acid showed equivalent tumor burden to vehicle mice (P < .001 G-CSF vs vehicle; P = .48 G-CSF plus zoledronic acid vs vehicle; pooled data from 3 independent experiments; y-axis is log scale). (B) After tumor cells were injected (7 days), mice were killed and bones were isolated. Histomorphometric analysis confirmed the increased tumor burden seen by imaging in the G-CSF–administered animals (P = .046). Representative histology depicted here; M indicates marrow; T, tumor. All error bars represent standard error of the mean. Asterisks denote statistical significance.