•  
     
     
    Type Size
     
    ASBMR 31st Annual Meeting

    Systemic Treatment with a Sclerostin Monoclonal Antibody Enhances Fracture Healing in the Rat Femoral Closed Fracture Model

    Categories:
     Bone, Cartilage and Connective Tissue Matrix & Development (Basic)
     Bone Biomechanics and Quality (Clinical)
     Osteoporosis - Treatment (Preclinical)

    Poster Sessions, Presentation Number: SU0407
    Session: Poster Session II
    Sunday, September 13, 2009 12:00 AM - 12:00 AM, Colorado Convention Center, Exhibit Hall F

    * Chaoyang Li, Amgen Inc., USA, Xiaodong Li, Amgen Inc., USA, Juanjuan Xiang, Queen's University of Belfast, United Kingdom, Hong-Lin Tan, Amgen Inc., USA, Mauricio Barrero, Amgen Inc., USA, Qing-Tian Niu , Amgen Inc., USA, Franklin Asuncion, Amgen Inc., USA, Michael Ominsky, Amgen Inc., USA, Paul Kostenuik , Amgen Inc., USA, William "Scott" Simonet , Amgen Inc., USA, Chris Paszty, Amgen Inc., USA, Gang Li, Queen's university, United Kingdom, Hua Zhu "David" Ke, Amgen Inc., USA

    We have previously reported that inhibition of sclerostin by systemic treatment with a sclerostin monoclonal antibody (Scl-Ab) significantly increased bone formation, bone mass and bone strength in animal models of osteoporosis. Fracture healing is a complex biological process, and bone formation is an important part of this process. The purpose of these studies was to test the effects of Scl-Ab on the rat femoral closed fracture model. In the first study, 9-week-old male SD rats underwent standard closed mid-diaphyseal femoral fracture. After surgery, the rats were subcutaneously (sc) injected with vehicle (n=9) or a Scl-Ab (Scl-AbIII) at 25 mg/kg (n=8), twice per week for 4 weeks. In addition, there was 1 group of rats treated with Scl-AbIII for the first 2 weeks, and then with vehicle for the next 2 weeks (on/off treatment, n=12). Effects were monitored by weekly X-ray analysis, and fractured femurs were excised for mechanical testing. In the second study, standard closed mid-diaphyseal femoral fracture was performed in 10-week-old male SD rats. These rats were injected sc with vehicle (n=8) or a Scl-Ab (Scl-AbIII, n=6) at 25 mg/kg, twice per week, for 4 weeks. Longitudinal sections of the fracture site were analyzed by bone histomorphometric methods. Analysis of X-ray images from the first study showed that the 4-week treatment group and the on/off treatment group had improved callus density compared to vehicle treatment controls. Maximum load and stiffness of fractured femurs in the on/off treatment group were increased by 105% and 110%, respectively, and in the 4-week treatment group by 54% and 70%, respectively, compared with the vehicle group. In the second study, histologic examination indicated that there was more bony tissue in the fracture callus and fracture gap in rats treated with Scl-AbIII compared with vehicle controls. This result indicated that Scl-Ab stimulated bone formation in the fracture callus and fracture gap; thus increased bridging of fracture sites. In summary, Scl-Ab treatment improved fracture healing in the closed femoral fracture rat model. These data suggest that inhibition of sclerostin by systemic administration of Scl-Ab may be an attractive, non-invasive strategy to enhance fracture healing.

    Disclosures: C. Paszty, Amgen: Employment (full or part-time). W. Simonet , Amgen: Employment (full or part-time). H. Tan, Amgen: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. M. Ominsky, Amgen: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. C. Li, Amgen: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. F. Asuncion, Amgen: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. . Niu , Amgen: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. F. Asuncion, Amgen: Employment (full or part-time). J. Xiang, Amgen: Research Grants. . Niu , Amgen: Employment (full or part-time). M. Ominsky, Amgen: Employment (full or part-time). G. Li, Amgen: Research Grants. . Kostenuik , Amgen: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. M. Barrero, Amgen: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. . Kostenuik , Amgen: Employment (full or part-time). M. Barrero, Amgen: Employment (full or part-time). H. Ke, Amgen: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. H. Ke, Amgen: Employment (full or part-time). C. Li, Amgen: Employment (full or part-time). G. Li, Amgen: Consulting fees or other remuneration (payment). X. Li, Amgen: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. W. Simonet , Amgen: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. H. Tan, Amgen: Employment (full or part-time). X. Li, Amgen: Employment (full or part-time). C. Paszty, Amgen: Stock options or bond holdings in a for-profit corporation or self-directed pension plan.

    * Presenting Authors(s): Chaoyang Li, Amgen Inc., USA