Inhibition of sclerostin by monoclonal antibody enhances bone healing and improves bone density and strength of nonfractured bones |
| |
Authors: | Michael S Ominsky Chaoyang Li Xiaodong Li Hong L Tan Edward Lee Mauricio Barrero Franklin J Asuncion Denise Dwyer Chun‐Ya Han Fay Vlasseros Rana Samadfam Jacquelin Jolette Susan Y Smith Marina Stolina David L Lacey William S Simonet Chris Paszty Gang Li Hua Z Ke |
| |
Institution: | 1. Metabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA;2. Bone Research, Preclinical Services, Charles River Laboratories, Montreal, Quebec, Canada;3. Stem Cell and Regeneration Program, Li Ka Shing Institute of Health Sciences, School of Biomedical Sciences and Department of Orthopaedics and Traumatology, Chinese University of Hong Kong, Hong Kong, SAR China |
| |
Abstract: | Therapeutic enhancement of fracture healing would help to prevent the occurrence of orthopedic complications such as nonunion and revision surgery. Sclerostin is a negative regulator of bone formation, and treatment with a sclerostin monoclonal antibody (Scl‐Ab) results in increased bone formation and bone mass in animal models. Our objective was to investigate the effects of systemic administration of Scl‐Ab in two models of fracture healing. In both a closed femoral fracture model in rats and a fibular osteotomy model in cynomolgus monkeys, Scl‐Ab significantly increased bone mass and bone strength at the site of fracture. After 10 weeks of healing in nonhuman primates, the fractures in the Scl‐Ab group had less callus cartilage and smaller fracture gaps containing more bone and less fibrovascular tissue. These improvements at the fracture site corresponded with improvements in bone formation, bone mass, and bone strength at nonfractured cortical and trabecular sites in both studies. Thus the potent anabolic activity of Scl‐Ab throughout the skeleton also was associated with an anabolic effect at the site of fracture. These results support the potential for systemic Scl‐Ab administration to enhance fracture healing in patients. © 2011 American Society for Bone and Mineral Research. |
| |
Keywords: | FRACTURE HEALING SCLEROSTIN SCLEROSTIN ANTIBODY WNT STRENGTH |
|
|