Blockade of the colony-stimulating factor-1 receptor reverses bone loss in osteoporosis mouse models

Mice lacking either colony-stimulating factor-1 (CSF-1) or its receptor, CSF-1R, display osteopetrosis. Accordingly, genetic deletion or pharmacological blockade of CSF-1 prevents the bone loss associated with estrogen deficiency. However, the role of CSF-1R in osteoporosis models of type-1 diabetes (T1D) and ovariectomy (OVX) has not been examined. Thus, we evaluated whether CSF-1R blockade would relieve the bone loss in a model of primary osteoporosis (female mice with OVX) and a model of secondary osteoporosis (female with T1D) using micro-computed tomography.

Female ICR mice at 10 weeks underwent OVX or received five daily administrations of streptozotocin (ip, 50 mg/kg) to induce T1D. Four weeks after OVX and 14 weeks after first injection of streptozotocin, mice received an anti-CSF-1R (2G2) antibody (10 mg/kg, ip; once/week for 6 weeks) or vehicle. At the last day of antibody administration, mice were sacrificed and femur and tibia were harvested for micro-computed tomography analysis.

Mice with OVX had a significant loss of trabecular bone at the distal femoral and proximal tibial metaphysis. Chronic treatment with anti-CSF-1R significantly reversed the trabecular bone loss at these anatomical sites. Streptozotocin-induced T1D resulted in significant loss of trabecular bone at the femoral neck and cortical bone at the femoral mid-diaphysis. Chronic treatment with anti-CSF-1R antibody significantly reversed the bone loss observed in mice with T1D.

Our results demonstrate that blockade of CSF-1R signaling reverses bone loss in two different mouse models of osteoporosis.