Enhanced tumor growth in bone following G-CSF administration is not seen in OC-defective mice. (A) RT-PCR was performed on mRNA harvested from murine tumor cell lines. Parental 4T1 and 4T1-GFP-FL cells express Rank-r, while B16 and B16-FL cells do not. (B) OPG^Tg or wild-type mice were administered 200 μg/kg G-CSF or drug vehicle daily for 8 days. On the fifth day of treatment, 10⁴ B16-FL tumor cells were injected into the right tibia. Tumor burden was assessed by bioluminescence imaging on days 8 and 10 after tumor cell injection. G-CSF–administered wild-type mice (n = 12) demonstrated an increased tumor burden compared with vehicle-administered animals (n = 17; P = .057), while OPG^Tg mice demonstrated equivalent tumor growth (n = 16 vehicle-administered OPG^Tg mice, n = 20 G-CSF–administered OPG^Tg mice; P = .64; results were pooled from 5 independent experiments; y-axis is log scale). (C) Histomorphometric analysis confirmed the increased tumor burden seen by imaging in the G-CSF–administered wild-type mice (P < .001 wild-type, P = 0.24 OPG^Tg). Representative histology depicted here. M indicates marrow; T, tumor. (D) DEXA was used to measure BMD on formalin-fixed bones. G-CSF–administered wild-type mice (n = 10) showed an 8% decrease in BMD compared with vehicle-administered controls (n = 13; P = .004), while G-CSF–administered OPG^Tg mice (n = 11) demonstrated equivalent BMD compared with vehicle-administered controls (n = 9; P = .06). All error bars represent standard error of the mean. Asterisks indicate statistical significance.