title: Steroid-associated hip joint collapse in bipedal emus.
abstract: In this study we established a bipedal animal model of steroid-associated hip joint collapse in emus for testing potential treatment protocols to be developed for prevention of steroid-associated joint collapse in preclinical settings. Five adult male emus were treated with a steroid-associated osteonecrosis (SAON) induction protocol using combination of pulsed lipopolysaccharide (LPS) and methylprednisolone (MPS). Additional three emus were used as normal control. Post-induction, emu gait was observed, magnetic resonance imaging (MRI) was performed, and blood was collected for routine examination, including testing blood coagulation and lipid metabolism. Emus were sacrificed at week 24 post-induction, bilateral femora were collected for micro-computed tomography (micro-CT) and histological analysis. Asymmetric limping gait and abnormal MRI signals were found in steroid-treated emus. SAON was found in all emus with a joint collapse incidence of 70%. The percentage of neutrophils (Neut %) and parameters on lipid metabolism significantly increased after induction. Micro-CT revealed structure deterioration of subchondral trabecular bone. Histomorphometry showed larger fat cell fraction and size, thinning of subchondral plate and cartilage layer, smaller osteoblast perimeter percentage and less blood vessels distributed at collapsed region in SAON group as compared with the normal controls. Scanning electron microscope (SEM) showed poor mineral matrix and more osteo-lacunae outline in the collapsed region in SAON group. The combination of pulsed LPS and MPS developed in the current study was safe and effective to induce SAON and deterioration of subchondral bone in bipedal emus with subsequent femoral head collapse, a typical clinical feature observed in patients under pulsed steroid treatment. In conclusion, bipedal emus could be used as an effective preclinical experimental model to evaluate potential treatment protocols to be developed for prevention of ON-induced hip joint collapse in patients.
authors.affiliation: Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Li-Zhen
authors.initials: LZ
authors.lastname: Zheng
authors.forename: Zhong
authors.initials: Z
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Lei
authors.forename: Jiang
authors.initials: J
authors.lastname: Peng
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: He
authors.forename: Xin-Hui
authors.initials: XH
authors.lastname: Xie
authors.forename: Chi-Wai
authors.initials: CW
authors.lastname: Man
authors.forename: Le
authors.initials: L
authors.lastname: Huang
authors.forename: Xin-Luan
authors.initials: XL
authors.lastname: Wang
authors.forename: Daniel Tik-Pui
authors.initials: DT
authors.lastname: Fong
authors.forename: De-Ming
authors.initials: DM
authors.lastname: Xiao
authors.forename: Da-Ping
authors.initials: DP
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.forename: Jian Q
authors.initials: JQ
authors.lastname: Feng
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020312:Dromaiidae; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology / Q000648:ultrastructure; D006621:Hip Joint / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D050356:Lipid Metabolism; D008070:Lipopolysaccharides; D008279:Magnetic Resonance Imaging; D008775:Methylprednisolone; D008855:Microscopy, Electron, Scanning; D009504:Neutrophils / Q000473:pathology; D010020:Osteonecrosis / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000473:pathology*; D055114:X-Ray Microtomography
chemical_list: D008070:Lipopolysaccharides; D008775:Methylprednisolone