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    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

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

    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): , UNITED STATES