Granulocyte colony-stimulating factor administration alters femoral biomechanical properties in C57BL/6 mice

The clinical application of G-CSF is broadening. In addition to treating neutropenia and in bone marrow transplants, it is now being considered for functional recovery after myocardial infarction and stroke. It is thus very important that the effects of extended G-CSF administration on the skeleton are investigated. To simulate this potential clinical use of G-CSF in postmyocardial infarction or cerebral vascular accident, a 2-week course of administration was selected. Ten C57BL/6 mice at 22 weeks of age were given intraperitoneal injection of saline, and another nine of the same age were given G-CSF. Four weeks later, femurs were harvested and three-point-bend tests were performed until fracture. From the load-displacement curve recorded during the test, the stiffness, Young's modulus, fracture strength of the bone, fracture energy, and the total energy to break the femur were determined. The test data show that mice treated with G-CSF have significantly lower modulus in their femurs when compared to the controlled mice treated with saline. The stiffness demonstrates the largest decrease, by as much as 25%. As its clinical use increases, G-CSF effects on the mechanical properties of the skeleton become increasingly more important because many of these diseases occur in older patients with already compromised skeleton by osteopenia or osteoporosis. How G-CSF administration achieves these alterations in skeletal biomechanical properties is unclear. Although the current findings confirm its known temporary catabolic effects on bone homeostasis, it also suggests that a transient state of higher bone compliance following the end of G-CSF administration can be achieved that may have clinical benefits.