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    ASBMR 31st Annual Meeting

    Bone Implant Fixation Augmentation with Anti-Sclerostin Antibody Treatment in Rats

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

    Poster Sessions, Presentation Number: MO0018
    Session: Poster Session III
    Monday, September 14, 2009 12:00 AM - 12:00 AM, Colorado Convention Center, Exhibit Hall F

    * , UNITED STATES, , JAPAN, James Maletich, Rush University Medical Center, , UNITED STATES, , UNITED KINGDOM, , UNITED STATES

    Sclerostin is a secreted protein known to inhibit osteoblast activity and subsequent bone formation in both rats and humans. Previous studies have demonstrated a positive correlation between bone anabolism and sclerostin blockade using a monoclonal antibody. This study evaluates the potential benefit of using anti-sclerostin treatment in joint replacement in terms of enhanced peri-implant bone formation with improved bone implant fixation. Titanium cylinders were implanted in the distal femurs of two groups of rats (Sprague-Dawley, male, N=90). One of the groups received murine anti-sclerostin antibody (Scl-AbII, Amgen) while the other received saline and acted as a control group. Both treatments were administered subcutaneously via injections (25 mg/kg), two times each week for the duration of the study. Rats from both groups were sacrificed at 2, 4, and 8 weeks post implant surgery. The femurs were harvested and subjected to micro-CT (to evaluate peri-implant bone volume/tissue volume {BV/TV}) and mechanical pull-out test (to assess implant fixation parameters). BV/TV had a significant time-by-group interaction term (p < 0.001) because of a time-dependent decrease in this variable in all groups except the Scl-AbII group, which showed an increase in peri-implant BV/TV at 8 weeks. The rats treated with the antibody for 2 weeks showed no significant difference in load to failure (strength), stiffness, and energy to failure of the bone-implant interface. At 4 weeks, however, the animals treated with antibody showed a 1.9-fold increase in mean strength (p=0.024) and a 4.0-fold increase in mean energy to failure (p=0.002) compared to their saline counterparts. By 8 weeks, increases in the mean value of all parameters were significantly higher for the animals treated with the antibody compared to saline treatment; showing increases of 2.2-fold (p<0.001), 1.8-fold (p=0.002), and 2.9-fold (p<0.001) in strength, stiffness, and energy to failure, respectively. These results indicate anti-sclerostin antibody treatment during bone regeneration around an implant provides elevated BV/TV with not only enhanced but also accelerated implant fixation that is evident by 4 weeks and continues through at least 8 weeks of treatment.

    Disclosures: A. Virdi, Amgen Inc: Research Grants. M. Liu, Amgen Inc: Employment (full or part-time). D. Sumner, Amgen Inc: Research Grants. H. Ke, Amgen Inc: Employment (full or part-time). K. Sena, Amgen Inc: Research Grants.

    * Presenting Authors(s): , UNITED STATES