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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 4/2010

Open Access 01-08-2010 | Research article

Subchondral bone microstructural damage by increased remodelling aggravates experimental osteoarthritis preceded by osteoporosis

Authors: Miriam Bellido, Laura Lugo, Jorge A Roman-Blas, Santos Castañeda, Jose R Caeiro, Sonia Dapia, Emilio Calvo, Raquel Largo, Gabriel Herrero-Beaumont

Published in: Arthritis Research & Therapy | Issue 4/2010

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Abstract

Introduction

Osteoporosis (OP) increases cartilage damage in a combined rabbit model of OP and osteoarthritis (OA). Accordingly, we assessed whether microstructure impairment at subchondral bone aggravates cartilage damage in this experimental model.

Methods

OP was induced in 20 female rabbits, by ovariectomy and intramuscular injections of methylprednisolone hemisuccinate for four weeks. Ten healthy animals were used as controls. At week 7, OA was surgically induced in left knees of all rabbits. At 22 weeks, after sacrifice, microstructure parameters were assessed by micro-computed tomography, and osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), alkaline phosphatase (ALP) and metalloproteinase 9 (MMP9) protein expressions were evaluated by Western Blot at subchondral bone. In addition, cartilage damage was estimated using the histopathological Mankin score. Mann-Whitney and Spearman statistical tests were performed as appropriate, using SPSS software v 11.0. Significant difference was established at P < 0.05.

Results

Subchondral bone area/tissue area, trabecular thickness and polar moment of inertia were diminished in OPOA knees compared with control or OA knees (P < 0.05). A decrease of plate thickness, ALP expression and OPG/RANKL ratio as well as an increased fractal dimension and MMP9 expression occurred at subchondral bone of OA, OP and OPOA knees vs. controls (P < 0.05). In addition, the severity of cartilage damage was increased in OPOA knees vs. controls (P < 0.05). Remarkably, good correlations were observed between structural and remodelling parameters at subchondral bone, and furthermore, between subchondral structural parameters and cartilage Mankin score.

Conclusions

Microstructure impairment at subchondral bone associated with an increased remodelling aggravated cartilage damage in OA rabbits with previous OP. Our results suggest that an increased subchondral bone resorption may account for the exacerbation of cartilage damage when early OA and OP coexist simultaneously in same individuals.
Appendix
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Metadata
Title
Subchondral bone microstructural damage by increased remodelling aggravates experimental osteoarthritis preceded by osteoporosis
Authors
Miriam Bellido
Laura Lugo
Jorge A Roman-Blas
Santos Castañeda
Jose R Caeiro
Sonia Dapia
Emilio Calvo
Raquel Largo
Gabriel Herrero-Beaumont
Publication date
01-08-2010
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 4/2010
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar3103

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