A clinically realistic large animal model of intra-articular fracture that progresses to post-traumatic osteoarthritis

J.E Goetz; D Fredericks; E Petersen; M.J Rudert; T Baer; E Swanson; N Roberts; J Martin; Y Tochigi

doi:10.1016/j.joca.2015.05.022

$A clinically realistic large animal model of intra-articular fracture that progresses to post-traumatic osteoarthritis$

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A clinically realistic large animal model of intra-articular fracture that progresses to post-traumatic osteoarthritis

J.E Goetz, D Fredericks, E Petersen, M.J Rudert, T Baer, E Swanson, N Roberts, J Martin and Y Tochigi

Osteoarthritis and cartilage, Vol.23(10), pp.1797-1805

10/2015

DOI: 10.1016/j.joca.2015.05.022

PMID: 26033166

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Abstract

Translation of promising treatments for post-traumatic osteoarthritis (PTOA) to patients with intra-articular fracture (IAF) has been limited by the lack of a realistic large animal model. To address this issue we developed a large animal model of IAF in the distal tibia of Yucatan minipigs and documented the natural progression of this injury. Twenty-two fractures were treated using open reduction and internal fixation with either an anatomic reduction or an intentional 2-mm step-off. Pre-operatively, and 3 days, 1, 2, 4, 8, and 12 weeks post-operatively, animals were sedated for synovial fluid draws and radiographs. Limb loading was monitored at the same time points using a Tekscan Walkway. Animals were sacrificed at 12 weeks and the limbs were harvested for histological evaluation. All animals achieved bony union by 12 weeks, facilitating nearly complete recovery of the initial 60% decrease in limb loading. TNFα, IL1β, IL6, and IL8 concentrations in the fractured limbs were elevated (P < 0.05) at specific times during the 2 weeks after fracture. Histological cartilage degeneration was more severe in the step-off group (0.0001 < P < 0.27 compared to normal) than in the anatomic reconstruction group (0.27 < P < 0.99 compared to normal). This model replicated key features of a human IAF, including surgical stabilization, inflammatory responses, and progression to osteoarthritic cartilage degeneration, thereby providing a potentially useful model for translating promising treatment options to clinical practice.

Yucatan minipig

Post-traumatic osteoarthritis

Intra-articular fracture

Closed fracture

Details

Title: Subtitle: A clinically realistic large animal model of intra-articular fracture that progresses to post-traumatic osteoarthritis
Creators: J.E Goetz - Department of Orthopaedics & Rehabilitation, University of Iowa, Iowa City, IA, USA
D Fredericks - Department of Orthopaedics & Rehabilitation, University of Iowa, Iowa City, IA, USA
E Petersen - Department of Orthopaedics & Rehabilitation, University of Iowa, Iowa City, IA, USA
M.J Rudert - Department of Orthopaedics & Rehabilitation, University of Iowa, Iowa City, IA, USA
T Baer - Department of Orthopaedics & Rehabilitation, University of Iowa, Iowa City, IA, USA
E Swanson - Department of Bioengineering, University of Washington, Seattle, WA, USA
N Roberts - Department of Orthopaedics & Rehabilitation, University of Iowa, Iowa City, IA, USA
J Martin - Department of Orthopaedics & Rehabilitation, University of Iowa, Iowa City, IA, USA
Y Tochigi - Department of Orthopaedics, Dokkyo Medical University Koshigaya Hospital, Saitama, Japan
Resource Type: Journal article
Publication Details: Osteoarthritis and cartilage, Vol.23(10), pp.1797-1805
DOI: 10.1016/j.joca.2015.05.022
PMID: 26033166
NLM abbreviation: Osteoarthritis Cartilage
ISSN: 1063-4584
eISSN: 1522-9653
Publisher: Elsevier Ltd
Grant note: DOI: 10.13039/100000005, name: US Department of Defense, award: W81XWH-10-1-0864
Language: English
Date published: 10/2015
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Craniofacial Anomalies Research Center; Nursing
Record Identifier: 9984040340102771

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