• Bone · Dec 2011

    Increased callus mass and enhanced strength during fracture healing in mice lacking the sclerostin gene.

    • Chaoyang Li, Michael S Ominsky, Hong-Lin Tan, Mauricio Barrero, Qing-Tian Niu, Franklin J Asuncion, Edward Lee, Min Liu, William S Simonet, Chris Paszty, and Hua Zhu Ke.
    • Department of Metabolic Disorders, Amgen Inc., Thousand Oaks, CA 91320-1799, USA. chaoyang@amgen.com
    • Bone. 2011 Dec 1; 49 (6): 1178-85.

    AbstractHumans with inherited sclerostin deficiency have high bone mass. Targeted deletion of the sclerostin gene in mice (SOST-KO) causes increases in bone formation, bone mass and bone strength. Inhibition of sclerostin by a monoclonal antibody increases bone formation and enhances fracture healing in rodent and primate models. In this study, we describe the temporal progression of femoral fracture healing in SOST-KO mice compared with wild type (WT) control mice to further characterize the role of sclerostin in fracture healing. Sixty-seven male 9-10 week-old SOST-KO (N=37) and WT (N=30) mice underwent a closed femoral fracture. Weekly radiography was used to monitor the progress of healing. Histologic sections were used to characterize callus composition, evaluate callus bridging, and quantify lamellar bone formation on days 14 and 28. Densitometry and biomechanical testing were utilized to characterize bone mass and strength at the fractured and contralateral femurs on day 45. A significant improvement in time to radiographic healing (no discernible fracture line) was observed in SOST-KO mice, which corresponded to an increase in histologic bony bridging at 14 days (38% versus 0% in WT). Both genotypes appeared to be nearly fully bridged at 28 days post-fracture. The increased bridging at 14 days was associated with 97% greater bone area and 40% lower cartilage area in the callus of SOST-KO mice as compared to WT mice. Bone formation-related endpoints were higher in SOST-KO mice at both 14 and 28 days. At 45 days post-fracture, peak load and bone mass were significantly greater in the fractured femurs of SOST-KO mice as compared to WT mice. In conclusion, fractures in mice lacking sclerostin showed accelerated bridging, greater callus maturation, and increased bone formation and strength in the callus.Copyright © 2011 Elsevier Inc. All rights reserved.

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