Systemic administration of sclerostin monoclonal antibody accelerates fracture healing in the femoral osteotomy model of young rats

• Sclerostin antibody improves the expression of PCNA and BMP-2.
• Sclerostin antibody reduces the cartilage fraction in the callus.
• Sclerostin antibody accelerates fracture healing.
• Sclerostin antibody shows significant anabolic effects in intact femur.

Genetic studies have demonstrated that sclerostin was a key negative regulator of bone formation. Sclerostin monoclonal antibody (Scl-Ab) treatment enhanced bone healing in experimental fracture healing. The purpose was to investigate the effects of systemic Scl-Ab administration on open fracture healing in young rats. Unilateral femoral fractures were generated in eight-week-old Sprague–Dawley rats. Rats were treated with vehicle or Scl-Ab for 6 weeks. Fracture healing was evaluated by western blotting, immunohistochemistry, histology, radiography, micro-CT, and biomechanical testing. In addition, the bone mass of intact femur was also evaluated by micro-CT. The results showed that, at 1 and 2 weeks after fracture, proliferating cell nuclear antigen (PCNA) score and bone morphogenetic protein-2 (BMP-2) expression in the Scl-Ab group were significantly increased compared with the control group. A decrease in cartilage in the Scl-Ab group was also observed after fracture, and this was accompanied by more rapider fracture healing. At 4 and 6 weeks, there were significant increases in bone mass and mechanical properties in the calluses from Scl-Ab group compared with control group. In addition, Scl-Ab treatment also showed significant anabolic effects in intact femur. In conclusion, systemic Scl-Ab administration has a significant enhancement in a rat femoral osteotomy model. These results support the therapeutic potential of Scl-Ab as a noninvasive strategy to enhance open fracture healing.