PMID- 23728104 OWN - NLM STAT- MEDLINE DCOM- 20140109 LR - 20201209 IS - 1108-7161 (Print) IS - 1108-7161 (Linking) VI - 13 IP - 2 DP - 2013 Jun TI - Time-dependent effects of sclerostin antibody on a mouse fracture healing model. PG - 178-84 AB - OBJECTIVES: 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. FAU - Cui, L AU - Cui L AD - Guangdong Key Laboratory for R&D of Natural Drug, Guangdong Medical College, Zhanjiang 524023, Guangdong, PR China. FAU - Cheng, H AU - Cheng H FAU - Song, C AU - Song C FAU - Li, C AU - Li C FAU - Simonet, W S AU - Simonet WS FAU - Ke, H Z AU - Ke HZ FAU - Li, G AU - Li G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - J Musculoskelet Neuronal Interact JT - Journal of musculoskeletal & neuronal interactions JID - 101084496 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Antibodies) RN - 0 (Glycoproteins) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Sost protein, mouse) SB - IM MH - Adaptor Proteins, Signal Transducing MH - Animals MH - Antibodies/*pharmacology MH - Biomechanical Phenomena MH - Bone Density/drug effects MH - Femoral Fractures/diagnostic imaging/drug therapy MH - Fracture Healing/*drug effects MH - Fractures, Bone/diagnostic imaging/*drug therapy MH - Glycoproteins/*immunology MH - Image Processing, Computer-Assisted MH - Intercellular Signaling Peptides and Proteins MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Microscopy, Fluorescence MH - Osteotomy MH - Tissue Fixation MH - Tomography, X-Ray Computed EDAT- 2013/06/04 06:00 MHDA- 2014/01/10 06:00 CRDT- 2013/06/04 06:00 PHST- 2013/06/04 06:00 [entrez] PHST- 2013/06/04 06:00 [pubmed] PHST- 2014/01/10 06:00 [medline] PST - ppublish SO - J Musculoskelet Neuronal Interact. 2013 Jun;13(2):178-84.