Exploring an Anabolic Approach to Address Nonunion After Bone Fracture: Commentary on an article by Brian A. Tinsley, MD, et al.: "Systemic Administration of Sclerostin Antibody Enhances Bone Morphogenetic Protein-Induced Femoral Defect Repair in a Rat Model".

Abstract

Nonunion is not uncommon across all fracture types, and in complex open or high-energy fractures, the rates of delayed union and nonunion increase dramatically. The tibia, in particular, is often involved in high-energy open fractures, and the tibia has a more tenuous blood supply than other long bones, resulting in a nonunion rate of nearly 30%1. In addition to prolonged pain and disability for the patient, the financial and resource costs to the health-care system are higher with delayed union and nonunion. There are three potential objectives of any new therapeutic approach to address delayed union or nonunion: (1) to stimulate fractures that would eventually heal so that they heal more quickly, (2) to stimulate fractures that would otherwise proceed to nonunion to heal initially (prevention), and (3) to stimulate fractures that have experienced nonunion to heal more completely and more quickly on subsequent treatment. Sclerostin, which is released by osteocytes, is an antagonist of Wnt ligand and inhibits the canonical Wnt signaling pathway that is instrumental in bone formation through the activation of osteoblasts. Sclerostin antibody (Scl-Ab) exhibits potent anabolic effects in bone by binding sclerostin2. Scl-Ab recently was shown to improve bone density significantly in women with low bone mass3 and also has …