title: Time-dependent effects of sclerostin antibody on a mouse fracture healing model.
abstract: OBJECTIVE
  Treatment with Sclerostin antibody (Scl-Ab) has shown to enhance fracture healing in rodent and non-human primate models. The current study investigated the time-dependent changes during Scl-Ab treatment in a mouse osteotomy model.
  
  
  METHODS
  1 day after osteotomy, C57BL mice received subcutaneous injection with vehicle or Scl-Ab at 25 mg/kg, twice/week for 2, 4, or 6 weeks. 20 mice from each group were necropsied at weeks 2, 4, and 6 for Micro-CT, histomorphmetry and mechanical testing examinations.
  
  
  RESULTS
  The bone mineral apposition rate at fracture callus was significantly higher in the Scl-Ab treated groups at all the time points. Micro-CT analysis showed that the volumetric bone mineral density (vBMD) and bone volume over tissue volume (BV/TV) in the Scl-Ab treated groups at 4 and 6 weeks were significantly greater than that of vehicle control groups. Mechanical testing showed that the maximum load of failure at the fracture callus increased significantly by 68% at 6 weeks in the Scl-Ab treated groups.
  
  
  CONCLUSIONS
  This study confirmed that mice treated with Scl-Ab increased bone formation from 2 weeks, bone mineral density and bone volume at 4 weeks, followed by significant increase in bone strength at the fracture site at 6 weeks. These results suggest that applying sclerostin antibody at early stage fracture healing promotes fracture healing.
authors.affiliation: Guangdong Key Laboratory for R&D of Natural Drug, Guangdong Medical College, Zhanjiang 524023, Guangdong, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Cui
authors.forename: H
authors.initials: H
authors.lastname: Cheng
authors.forename: C
authors.initials: C
authors.lastname: Song
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: W S
authors.initials: WS
authors.lastname: Simonet
authors.forename: H Z
authors.initials: HZ
authors.lastname: Ke
authors.forename: G
authors.initials: G
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000188:drug therapy; D017102:Fracture Healing / Q000187:drug effects*; D050723:Fractures, Bone / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006023:Glycoproteins / Q000276:immunology*; D007091:Image Processing, Computer-Assisted; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D010027:Osteotomy; D016707:Tissue Fixation; D014057:Tomography, X-Ray Computed
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C486030:Sost protein, mouse