G-CSF enhances OC activity and increases bone resorption in vivo. (A) Serum was collected from mice 24 hours after completion of an 8-day course of 200 μg/kg G-CSF (n = 5) or vehicle (n = 5). Levels of TRAP 5b were measured by ELISA. G-CSF–administered mice have a 14% increase in levels of serum TRAP 5b (P = .03). (B) Mice were administered 200 μg/kg G-CSF (n = 19) or vehicle (n = 17) for 8 days. After the final dose (9 days), mice were killed and isolated femurs and tibias were fixed in formalin. BMD was measured on formalin-fixed bones by DEXA. Mice administered G-CSF demonstrated a 7% loss in BMD compared with vehicle-administered controls (P < .001). (C) Mice were administered 200 μg/kg G-CSF (n = 13) or vehicle (n = 17) for 8 days. After the final dose (9 days), mice were killed and tibial bones were isolated, decalcified and TRAP-stained to visualize OCs. G-CSF–administered mice had a statistically significant increase in OC perimeter and decrease in trabecular bone area compared with vehicle-administered mice (P = .02 and P < .005, respectively). (D) Representative histology of vehicle-administered versus G-CSF–administered mice. (E) G-CSF–administered animals (n = 3) demonstrated elevated neutrophil counts compared with vehicle-administered animals (n = 3; P = .01). All error bars represent standard error of the mean. Asterisks indicate statistical significance.