Sclerostin Antibody Increases Callus Size and Strength but does not Improve Fracture Union in a Challenged Open Rat Fracture Model

Open fractures remain a challenge in orthopedics. Current strategies to intervene are often inadequate, particularly in severe fractures or when treatment is delayed. Sclerostin is a negative regulator of bone growth and sclerostin-neutralizing antibodies (Scl-Ab) can increase bone mass and strength...

Full description

Saved in:
Bibliographic Details
Published in:Calcified tissue international 2017-08, Vol.101 (2), p.217-228
Main Authors: Morse, Alyson, McDonald, Michelle M., Schindeler, Aaron, Peacock, Lauren, Mikulec, Kathy, Cheng, Tegan L., Liu, Min, Ke, Hua Zhu, Little, David G.
Format: Article
Language:English
Subjects:
Animals
Antibodies
Antibodies - pharmacology
Biochemistry
Biomechanical Phenomena - drug effects
Biomedical and Life Sciences
Bone Density - drug effects
Bone growth
Bone mass
Bone Morphogenetic Proteins - immunology
Bones
Bony Callus - pathology
Callus
Cell Biology
Cellular biology
Computed tomography
Disease Models, Animal
Endocrinology
Femoral Fractures - drug therapy
Femoral Fractures - pathology
Femur - drug effects
Femur - pathology
Fracture Healing - drug effects
Fractures
Genetic Markers - immunology
Immunoglobulins
Life Sciences
Male
Original Research
Orthopedics
Osteogenesis - drug effects
Osteotomy
Osteotomy - methods
Rats
Rodents
SOST protein
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Open fractures remain a challenge in orthopedics. Current strategies to intervene are often inadequate, particularly in severe fractures or when treatment is delayed. Sclerostin is a negative regulator of bone growth and sclerostin-neutralizing antibodies (Scl-Ab) can increase bone mass and strength. The application of these antibodies to improve orthopedic repair has shown varied results, and may be dependent on the location and severity of the bony injury. We examined Scl-Ab treatment within an established rat osteotomy model with periosteal stripping analogous to open fracture repair. In one study, Scl-Ab was given 25 mg/kg bi-weekly, either from the time of fracture or from 3 weeks post-fracture up to an end-point of 12 weeks. A second study treated only delayed union open fractures that did not show radiographic union by week 6 post-fracture. Outcome measures included radiographic union, microCT analysis of bone volume and architecture, and histology. In the first study, Scl-Ab given from either 0 or 3 weeks significantly improved callus bone volume (+52%, p  
ISSN:0171-967X
1432-0827
DOI:10.1007/s00223-017-0275-2