A sclerostin antibody enhances metaphyseal bone healing in rats

Introduction: Most fractures occur in osteoporotic cancellous bone in metaphyseal regions. The response to the trauma of inserting a screw in cancellous bone appears similar to metaphyseal fracture repair. The formation of new bone around a screw determines the strength of its fixation. Hence, the bone regenerative response can be measured as a pull-out force. Sclerostin, a secreted glycoprotein, is the product of the SOST gene. Lack of sclerostin causes increased bone formation and high bone mass in humans. Sclerostin blocks the LRP5/6 receptor, thus antagonizing Wnt signaling and increasing β-catenin degradation. Sclerostin is primarily and probably exclusively expressed in osteocytes, and it is believed to be a potent negative regulator of bone formation. Inhibition of sclerostin by a sclerostin antibody increased bone formation on trabecular, endocortical and periosteal surfaces, and increased trabecular and cortical bone mass . A sclerostin antibody enhanced fracture healing in both mouse and rat fracture models . We tested the hypothesis that systemic administration of a sclerostin antibody would enhance the regenerative response of traumatized cancellous bone, and thereby the fixation of an implanted screw in non-osteoporotic bone in rats.