title: Evaluation of the effects of systemic treatment with a sclerostin neutralizing antibody on bone repair in a rat femoral defect model.
abstract: Systemic administration of a sclerostin neutralizing antibody (Scl-Ab) has been shown to enhance fracture callus density and strength in several animal models. In order to further evaluate the potential of Scl-Ab to improve healing in a bone defect model,we evaluated Scl-Ab in a 3mm femoral defect in young male outbred rats. Scl-Ab was given either continuously for 6 or 12 weeks after surgery or with 2 weeks of delay for 10 weeks. Bone formation was assessed by radiographs, µ-CT, and histology. Complete bony union was achieved in only a few defects after 12 weeks of healing (Scl-Ab treated 5/30, vehicle treated 1/15). µ-CT evaluation demonstrated a significant increase in the BV/TV in the defect in the delayed treatment group (65%, p<0.05), but a non-significant increase in the continuous group (35%, p = 0.11) compared to control. However, both regimens induced an anabolic response in the bone proximal and distal to the defect and in the un-operated femurs. We demonstrate that treatment with Scl-Ab can enhance bone repair in a bone defect and in the surrounding host bone, but lacks the osteoinductive activity to heal it. This agent seems to be most effective in bone repair scenarios where there is cortical integrity.
authors.forename: Farhang
authors.initials: F
authors.lastname: Alaee
authors.forename: Mandeep S
authors.initials: MS
authors.lastname: Virk
authors.forename: Hezhen
authors.initials: H
authors.lastname: Tang
authors.forename: Osamu
authors.initials: O
authors.lastname: Sugiyama
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Adams
authors.forename: Marina
authors.initials: M
authors.lastname: Stolina
authors.forename: Denise
authors.initials: D
authors.lastname: Dwyer
authors.forename: Michael S
authors.initials: MS
authors.lastname: Ominsky
authors.forename: Hua Zhu
authors.initials: HZ
authors.lastname: Ke
authors.forename: Jay R
authors.initials: JR
authors.lastname: Lieberman
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing; D019485:Bone Morphogenetic Proteins / Q000276:immunology*; D005264:Femoral Fractures; D005269:Femur / Q000187:drug effects; D017102:Fracture Healing / Q000187:drug effects*; D005819:Genetic Markers / Q000276:immunology*; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055114:X-Ray Microtomography
chemical_list: D057134:Antibodies, Neutralizing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C486031:Sost protein, rat