Sclerostin monoclonal antibody enhanced bone fracture healing in an open osteotomy model in rats.
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.
Department of Orthopaedics and Traumatology, Lui Che Woo Institute of Innovation Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Pui Kit
PK
Suen
Yi-Xin
YX
He
Dick Ho Kiu
DH
Chow
Le
L
Huang
Chaoyang
C
Li
Hua Zhu
HZ
Ke
Michael S
MS
Ominsky
Ling
L
Qin
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D019485:Bone Morphogenetic Proteins / Q000276:immunology*; D002146:Bony Callus / Q000187:drug effects; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000473:pathology*; D005269:Femur / Q000187:drug effects / Q000473:pathology; D017102:Fracture Healing / Q000187:drug effects*; D005819:Genetic Markers / Q000276:immunology*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010027:Osteotomy; D051381:Rats; D055114:X-Ray Microtomography
D000911:Antibodies, Monoclonal; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C486031:Sost protein, rat
fracture healing; osteotomy; sclerostin; sclerostin monoclonal antibody