title: Effects of Sclerostin Antibody on the Healing of Femoral Fractures in Ovariectomised Rats.
abstract: The inhibition of sclerostin by the systemic administration of a monoclonal antibody (Scl-Ab) significantly increased bone mass and strength in fractured bones in animal models and non-fractured bones in ovariectomised (OVX) rats. In this study, the effects of Scl-Ab on healing were examined in a closed fracture model in OVX rats. Sixty Sprague-Dawley rats underwent an ovariectomy or a sham operation at 4 months of age, and a closed fracture of the right femur was performed 3 months later. Subcutaneous injections with Scl-Ab (25 mg/kg) or saline were then administered on day 1 after the fracture and twice a week for 8 weeks (n = 20 per group), at which time the fractured femurs were harvested for micro-computed tomography analysis, four-point bending mechanical testing and histomorphometric analysis to examine bone mass, bone strength and dynamic bone formation at the fracture site. The angiogenesis at the fracture site was also examined. Bone marrow stem cells were also isolated from the fractured bone to perform a colony-forming unit (CFU) assay and an alkaline phosphatase-positive (ALP(+)) CFU assay. OVX rats treated with Scl-Ab for 8 weeks had significantly increased bone mineral density and relative bone volume compared with OVX rats treated with saline. Similarly, maximum loading, energy to maximum load and stiffness in Scl-Ab-treated OVX rats were significantly higher than those in saline controls. The mineral apposition rate (MAR), mineralising surface (MS/BS) and bone formation rate (BFR/BS) were also significantly increased in Scl-Ab-treated group compared with the saline-treated group in OVX rats. Furthermore, the Scl-Ab-treated group had more CFUs and ALP(+) CFUs than the saline-treated group in OVX rats. No significant difference in angiogenesis at the fracture site was found between the groups. Our study demonstrated that Scl-Ab helped to increase bone mass, bone strength and bone formation at the fracture site in a closed femoral fracture model in OVX rats. Bone marrow stem cells in OVX rats injected with Scl-Ab also had increased CFUs and ALP(+) CFUs.
authors.affiliation: Department of Orthopaedics and Traumatology, Faculty of Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics and Traumatology, Faculty of Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Rui
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Tin Yan
authors.initials: TY
authors.lastname: Cheng
authors.affiliation: Department of Orthopaedics and Traumatology, Faculty of Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Orthopaedics and Traumatology, Faculty of Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics and Traumatology, Faculty of Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
authors.forename: Fanbiao
authors.initials: F
authors.lastname: Meng
authors.affiliation: Department of Orthopaedics and Traumatology, Faculty of Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
authors.forename: Wayne Yuk Wai
authors.initials: WY
authors.lastname: Lee
authors.affiliation: Department of Orthopaedics and Traumatology, Faculty of Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Metabolic Disorders, Amgen Inc., Thousand Oaks, California, USA.
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Metabolic Disorders, Amgen Inc., Thousand Oaks, California, USA.
authors.forename: Huazhu
authors.initials: H
authors.lastname: Ke
authors.affiliation: Department of Orthopaedics and Traumatology, Faculty of Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China. gangli@cuhk.edu.hk.|Stem Cells and Regenerative Medicine Laboratory, Lui Che Woo Institute of Innovative Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China. gangli@cuhk.edu.hk.|Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. gangli@cuhk.edu.hk.|The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, China. gangli@cuhk.edu.hk.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000737:chemistry*; D001835:Body Weight; D001854:Bone Marrow Cells / Q000166:cytology; D019485:Bone Morphogenetic Proteins / Q000737:chemistry*; D005260:Female; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000276:immunology*; D017102:Fracture Healing; D005819:Genetic Markers; D007279:Injections, Subcutaneous; D009389:Neovascularization, Pathologic; D010012:Osteogenesis; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology; D013314:Stress, Mechanical; D055114:X-Ray Microtomography
chemical_list: D000906:Antibodies; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C486031:Sost protein, rat; D000469:Alkaline Phosphatase
keywords: Fracture healing; Ovariectomy; Sclerostin antibody