Sclerostin antibody enhances bone formation in a rat model of distraction osteogenesis

ABSTRACT Neutralizing monoclonal sclerostin antibodies are effective in promoting bone formation at a systemic level and in orthopedic scenarios including closed fracture repair. In this study we examined the effects of sclerostin antibody (Scl‐Ab) treatment on regenerate volume, density, and streng...

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Veröffentlicht in:Journal of orthopaedic research 2018-04, Vol.36 (4), p.1106-1113
Hauptverfasser: McDonald, Michelle M., Morse, Alyson, Birke, Oliver, Yu, Nicole Y. C., Mikulec, Kathy, Peacock, Lauren, Schindeler, Aaron, Liu, Min, Ke, Hua Z., Little, David G.
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Sprache:eng
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Zusammenfassung:ABSTRACT Neutralizing monoclonal sclerostin antibodies are effective in promoting bone formation at a systemic level and in orthopedic scenarios including closed fracture repair. In this study we examined the effects of sclerostin antibody (Scl‐Ab) treatment on regenerate volume, density, and strength in a rat model of distraction osteogenesis. Surgical osteotomy was performed on 179 Sprague Dawley rats. After 1 week, rats underwent distraction for 2 weeks, followed by 6 weeks for consolidation. Two treatment groups received biweekly subcutaneous Scl‐AbIII (a rodent form of Scl‐Ab; 25 mg/kg), either from the start of distraction onward or restricted to the consolidation phase. These groups were compared to controls receiving saline. Measurement modalities included longitudinal DXA, ex vivo QCT, and microCT, tissue histology, and biomechanical four‐point bending tests. Bone volume was increased in both Scl‐Ab treatments regimens by the end of consolidation (+26–38%, p 
ISSN:0736-0266
1554-527X
DOI:10.1002/jor.23726