title: Inhibition of sclerostin by systemic treatment with sclerostin antibody enhances healing of proximal tibial defects in ovariectomized rats.
abstract: Recent studies suggest a possible role for inhibitors of sclerostin such as sclerostin antibody (Scl-Ab) as an anabolic treatment for osteoporosis. Since Scl-Ab has also been shown to potentiate bone repair, we examined the effect of Scl-Ab treatment in a metaphyseal defect repair model in ovariectomized (OVX) rats. Four weeks after OVX or sham surgery, 3 mm circular defects were created bilaterally in the proximal tibia of all rats. After defect surgery, Saline or 25 mg/kg Scl-Ab was administered twice weekly for 3 weeks. Of note, healing was advanced in the 1-week post-defect surgery in OVX controls over Sham controls, with increases in bone volume and fluorochrome labeling observed. However, by week 2, OVX controls fell significantly behind in the repair response compared with Sham controls. Scl-Ab treatment significantly increased bone volume in the defect in OVX rats over the 3-week time course as examined by either microCT or histology. Significant increases in bone formation via fluorochrome labeling of the new bone were observed with Scl-Ab treatment, while osteoclast parameters were not different. With its powerful anabolic potential, bone-specific activity, and potential for low dosing frequency, Scl-Ab treatment could provide enhanced bone repair, particularly in situations of compromised bone repair such as osteoporotic bone.
authors.affiliation: The Children's Hospital, Locked Bag 4001, Westmead, New South Wales 2145, Australia.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: McDonald
authors.forename: Alyson
authors.initials: A
authors.lastname: Morse
authors.forename: Kathy
authors.initials: K
authors.lastname: Mikulec
authors.forename: Lauren
authors.initials: L
authors.lastname: Peacock
authors.forename: Nicole
authors.initials: N
authors.lastname: Yu
authors.forename: Paul A
authors.initials: PA
authors.lastname: Baldock
authors.forename: Oliver
authors.initials: O
authors.lastname: Birke
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Hua Zhu
authors.initials: HZ
authors.lastname: Ke
authors.forename: David G
authors.initials: DG
authors.lastname: Little
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use*; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors*; D001861:Bone Regeneration; D001862:Bone Resorption; D005260:Female; D017102:Fracture Healing / Q000187:drug effects*; D005819:Genetic Markers; D010012:Osteogenesis; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000000981:diagnostic imaging / Q000473:pathology; D055114:X-Ray Microtomography
chemical_list: D000906:Antibodies; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C486031:Sost protein, rat