Effects of combined insulin-like growth factor 1 and macrophage colony-stimulating factor on the skeletal properties of mice

Insulin-like growth factor-1 (IGF-1) and macrophage colony-stimulating factor (MCSF) are critical to skeletal homeostasis. We investigated the effects of combined IGF-1 plus MCSF on mice. C57BL/6J mice, aged 7 weeks, were assigned to baseline, vehicle, IGF-1, MCSF, or combined IGF-1 plus MCSF (1 mg/kg/day each, n=12-13/group, 28-day duration). IGF-1 or MCSF had no effect on bone formation rate; however, IGF-1 plus MCSF produced a 169% increase in periosteal bone formation rate. Combined therapy increased femoral mechanical properties (+25% elastic force), while IGF-1, and MCSF alone did not. Combined therapy affected trabecular bone volume fraction (+40%), number (+13%), and spacing (-13%). MCSF produced similar trabecular changes, while IGF-1 had no effect. Combined therapy and MCSF alone increased bone mineral content. We have demonstrated the superior effects of combined IGF-1 and MCSF. Together, these agents may promote bone modeling to a greater extent than either therapy alone.