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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

    * Amarjit Virdi, Rush University Medical Center, USA, Kotaro Sena, Kagoshima University, JPN, James Maletich, Rush University Medical Center, USA, Min Liu, Amgen Inc., USA, Hua Zhu (David) Ke, Amgen Inc., USA, D. Rick Sumner, Rush University Medical Center, USA

    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): Amarjit Virdi, Rush University Medical Center, USA