Steroid-Associated Hip Joint Collapse in Bipedal Emus

Li-Zhen Zheng,Ge Zhang,Yi-Xin He,Ming Lei,Jian Q Feng,Le Huang,Daniel Tik-Pui Fong,Yang Chen,Xin-Hui Xie,Ling Qin,Jiang Peng,Chi-Wai Man,Da-Ping Wang,Zhong Liu,De-Ming Xiao,Ying Liu,Xin-Luan Wang

doi:10.1371/journal.pone.0076797

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.

Highlights

Steroid-associated osteonecrosis (SAON) is a common orthopaedic problem steroids are initially prescribed for many non-orthopedic medical conditions, such as systemic lupus erythematosus (SLE), organ transplantation, asthma, rheumatologic arthritis (RA), and severe acute respiratory syndrome (SARS) [1,2,3,4,5]
For the time course changes in serum parameters related to lipid metabolism, Total Cholesterol (TC) was significantly increased at each time point post-induction, and ratio between Low-Density Lipoprotein (LDL) and High-Density Lipoprotein (HDL) as well as LDL was significantly increased at each time point post-injection (p,0.05 for all) while Total Glycerin (TG) did not show significant increase post-induction (Figure 2B)
Using a combined pulsed LPS and MPS induction protocol previously established for SAON quadrupedal rabbits [11,13], the present study established a SAON model in bipedal emus characterized with subchondral bone deterioration and hip joint collapse, an experimental model mimicking human ON often developed at hip joint with femoral head collapse

Summary

Introduction

Steroid-associated osteonecrosis (SAON) is a common orthopaedic problem steroids are initially prescribed for many non-orthopedic medical conditions, such as systemic lupus erythematosus (SLE), organ transplantation, asthma, rheumatologic arthritis (RA), and severe acute respiratory syndrome (SARS) [1,2,3,4,5]. The aim of the current study was to establish a SAON model in bipedal emus, with potentials to bone structural deterioration with subsequent femoral head collapse, a condition seen in SAON patients attributed to similar biomechanics or loading ratio imposed onto the hip joint [23,24]. Such a model would be essential for testing strategies to be developed for potential clinical applications for prevention and treatment of steroid-associated joint collapse

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Conclusion