Biologa

Osteoarthritis and Cartilage 19 (2011) 1142e1149

Subchondral bone changes in three different canine models of osteoarthritis
K. Kuroki*, C.R. Cook, J.L. Cook
Comparative Orthopaedic Laboratory, University of Missouri, Columbia, MO, United States

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Article history:
Received 13 November 2010
Accepted 15 June 2011

Objective: To test the hypothesis that changesin subchondral bone are signi cantly different among three
canine models of osteoarthritis (OA).
Design: In 21 purpose-bred mongrel dogs, OA was induced in one knee joint via either anterior cruciate
ligament transection (ACLt; n ¼ 5), medial femoral condylar groove creation (GR; n ¼ 6), or medial
meniscal release (MR; n ¼ 5). Five dogs that had sham surgery (SH; n ¼ 5) in one knee joint servedas
controls. Lameness scoring was performed every 4 weeks. Twelve weeks after surgery, the knee joints
were examined by histology and histomorphometry.
Results: Articular cartilage pathology as determined by Mankin scores was signi cantly severe in all three
OA models compared to SH controls in the medial tibia (P < 0.001 to P ¼ 0.026). ACLt had signi cantly
thinner subchondral platethickness (Sp.Th) in both the medial and lateral tibias while MR had signi cantly thicker Sp.Th in the medial tibia compared to SH controls (P < 0.001 to P ¼ 0.011). Trabecular bone
volume (BV/TV) and trabecular bone thickness (Tb.Th) for ACLt were signi cantly less than SH controls in
the tibias (P < 0.001 to P ¼ 0.011). Tibial Sp.Th, BV/TV, and Tb.Th were all moderately to strongly
correlated withlameness scores obtained throughout the study period (r ¼ À0.436 to r ¼ À0.738,
P < 0.001 to P ¼ 0.047) while Mankin scores showed moderate to strong correlations with Sp.Th in each
OA model (r ¼ 0.465 to r ¼ 0.816, P < 0.001 to P ¼ 0.033).
Conclusions: Changes in Sp.Th are associated with articular cartilage damage while tibial Sp.Th and BV/TV
and Tb.Th appear to be all in uenced by jointloading alterations.
Ó 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Keywords:
Osteoarthritis
Subchondral plate
Trabecular bone
Canine model

Introduction
One of the major hurdles in making clinical progress toward
solving osteoarthritis (OA) is a complete understanding of disease
mechanisms that lead to initiation and progression ofthe disease.
While articular cartilage degradation is considered the hallmark of
OA, the “joint is an organ” concept is quickly being recognized
a fundamental to basic science and clinical assessments of OA1e3.
Among various non-articular cartilage components in the joint,
subchondral bone changes have been implicated as a key pathology
in OA initiation and progression4e7. It has beensuggested that
subchondral sclerosis contributes to accelerate OA via increasing
mechanical stress on overlying articular cartilage5. Subchondral
sclerosis, histologically characterized by increased subchondral
plate thickness (Sp.Th), has been demonstrated in late-stage knee
OA in human patients8,9 and in animal models10e12. However, the

* Address correspondence and reprint requests to: KeiichiKuroki, Comparative
Orthopaedic Laboratory, University of Missouri, 900 E. Campus Drive, Columbia, MO
65211, United States. Tel: 1-573-884-0603; Fax: 1-573-884-5444.
E-mail address: kurokik@missouri.edu (K. Kuroki).

nature of the subchondral changes in OA is not fully understood,
particularly in early stages of the disease. In addition, whether
subchondral changes are a cause or a resultof cartilage degradation
is still a subject for debate.
Animal models hold many of the keys to improve our understanding of the development of subchondral lesions in OA since
most clinical studies have dealt with advanced disease as diagnosis
of early OA is a challenge in human patients. However, information
regarding subchondral bone pathology in early OA in the literature
is inconsistent...