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Sclerostin monoclonal antibody enhanced bone fracture healing in an open osteotomy model in rats.

Abstract
Sclerostin is a negative regulator of bone formation. Sclerostin monoclonal antibody (Scl-Ab) treatment promoted bone healing in various animal models. To further evaluate the healing efficiency of Scl-Ab in osteotomy healing, we investigated the time course effects of systemic administration of Scl-Ab on fracture repair in rat femoral osteotomy model. A total of 120 six-month-old male SD rats were subjected to transverse osteotomy at the right femur mid-shaft. Rats were treated with vehicle or Scl-Ab treatment for 3, 6, or 9 weeks. Fracture healing was evaluated by radiography, micro-CT, micro-CT based angiography, 4-point bending mechanical test and histological assessment. Scl-Ab treatment resulted in significantly higher total mineralized callus volume fraction, BMD and enhanced neovascularization. Histologically, Scl-Ab treatment resulted in a significant reduction in fracture callus cartilage at week 6 and increase in bone volume at week 9, associated with a greater proportion of newly formed bone area at week 6 and 9 by fluorescence microscopy. Mechanical testing showed significantly higher ultimate load in Scl-Ab treatment group at week 6 and 9. This study has demonstrated that Scl-Ab treatment enhanced bone healing in a rat femoral osteotomy model, as reflected in increased bone formation, bone mass and bone strength.
AuthorsPui Kit Suen, Yi-Xin He, Dick Ho Kiu Chow, Le Huang, Chaoyang Li, Hua Zhu Ke, Michael S Ominsky, Ling Qin
JournalJournal of orthopaedic research : official publication of the Orthopaedic Research Society (J Orthop Res) Vol. 32 Issue 8 Pg. 997-1005 (Aug 2014) ISSN: 1554-527X [Electronic] United States
PMID24782158 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Chemical References
  • Antibodies, Monoclonal
  • Bone Morphogenetic Proteins
  • Genetic Markers
  • Sost protein, rat
Topics
  • Animals
  • Antibodies, Monoclonal (therapeutic use)
  • Bone Morphogenetic Proteins (immunology)
  • Bony Callus (drug effects)
  • Femoral Fractures (diagnostic imaging, pathology)
  • Femur (drug effects, pathology)
  • Fracture Healing (drug effects)
  • Genetic Markers (immunology)
  • Male
  • Neovascularization, Physiologic (drug effects)
  • Osteotomy
  • Rats
  • X-Ray Microtomography

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