No Effect of Long-Term Risedronate Use on Cartilage and Subchondral Bone in an Experimental Rabbit Model of Osteoarthritis

Osteoarthritis (OA) is the most prevalent degenerative joint disease in animals and humans. It is characterized by pain, articular cartilage damage and joint stiffness. It has been suggested that the status of the subchondral bone compartment plays an important role in the initiation and progression...

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Authors: González Cantalapiedra, Antonio; Fernández-Martín, Silvia; Permuy Mendaña, María; López Peña, Mónica; Muñoz Guzón, Fernando María
Format: Article
Publication date:2020
Country:España
Institution:Universidad de Santiago de Compostela (USC)
Repository:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Language:English
OAI Identifier:oai:minerva.usc.gal:10347/39051
Online Access:https://hdl.handle.net/10347/39051
Access Level:Open access
Keyword:Bisphosphonate
Bone
Cartilage
Osteoarthritis
Risedronate
Synovial membrane
Subchondral bone
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author González Cantalapiedra, Antonio
author2 Fernández-Martín, Silvia
Permuy Mendaña, María
López Peña, Mónica
Muñoz Guzón, Fernando María
author2_role author
author
author
author
author_browse Fernández-Martín, Silvia
González Cantalapiedra, Antonio
López Peña, Mónica
Muñoz Guzón, Fernando María
Permuy Mendaña, María
author_facet González Cantalapiedra, Antonio
Fernández-Martín, Silvia
Permuy Mendaña, María
López Peña, Mónica
Muñoz Guzón, Fernando María
author_role author
collection Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
description Osteoarthritis (OA) is the most prevalent degenerative joint disease in animals and humans. It is characterized by pain, articular cartilage damage and joint stiffness. It has been suggested that the status of the subchondral bone compartment plays an important role in the initiation and progression of OA. Bisphosphonates have been proposed as a potential disease-modifying treatment for OA, however their effectiveness is not yet clear. Twenty-four male adult New Zealand rabbits were used to evaluate the effects of risedronate on the subchondral bone quality and cartilage degradation in a long-term model of experimentally induced OA. Animals underwent an anterior cruciate ligament transection and partial medial meniscectomy or sham operation in only one knee, which was randomly chosen, using the contralateral as healthy control. Animals were divided into three groups (n = 8): untreated control group and sham surgery control group; both groups received only vehicle; and risedronate group, treated with 2.5 mg orally weekly for 24 weeks. Stifle joints were harvested and scanned using a high-resolution micro-CT to evaluate the subchondral plate and trabecular bone changes. The macroscopic evaluation and histological analysis were determined using an adapted Osteoarthritis Research Society International scoring scheme to assess the cartilage degeneration. The lateral and medial femoral condyle and tibial plateau were evaluated. Additionally, the histological synovial membrane assessment was carried out. Sample analysis showed that the experimental model induced osteoarthritic changes in the operated joints, whereas in sham-operated rabbits, almost no histological changes were observed on articular cartilage surfaces. In terms of macroscopic and histological analyses, risedronate-treated animals did not show improved cartilage health compared with untreated operated rabbits, but a slightly anti-inflammatory activity was observed in the synovial membrane. Risedronate administration showed a slight tendency to increase subchondral bone plate thickness in lateral compartments but, it did not show conservation of periarticular bone and was not be able to suppress the osteophyte formation. In conclusion, long-term risedronate use did not demonstrate a positive effect on reducing the cartilage damage, and failed to prevent the subchondral bone changes and osteophytogenesis in an experimental rabbit model of OA.
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language eng
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oai_identifier_str oai:minerva.usc.gal:10347/39051
publishDate 2020
publishDateSort 2020
publisher Frontiers Media S.A.
publisherStr Frontiers Media S.A.
reponame_str Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
spelling No Effect of Long-Term Risedronate Use on Cartilage and Subchondral Bone in an Experimental Rabbit Model of Osteoarthritis González Cantalapiedra, Antonio Fernández-Martín, Silvia Permuy Mendaña, María López Peña, Mónica Muñoz Guzón, Fernando María Bisphosphonate Bone Cartilage Osteoarthritis Risedronate Synovial membrane Subchondral bone Osteoarthritis (OA) is the most prevalent degenerative joint disease in animals and humans. It is characterized by pain, articular cartilage damage and joint stiffness. It has been suggested that the status of the subchondral bone compartment plays an important role in the initiation and progression of OA. Bisphosphonates have been proposed as a potential disease-modifying treatment for OA, however their effectiveness is not yet clear. Twenty-four male adult New Zealand rabbits were used to evaluate the effects of risedronate on the subchondral bone quality and cartilage degradation in a long-term model of experimentally induced OA. Animals underwent an anterior cruciate ligament transection and partial medial meniscectomy or sham operation in only one knee, which was randomly chosen, using the contralateral as healthy control. Animals were divided into three groups (n = 8): untreated control group and sham surgery control group; both groups received only vehicle; and risedronate group, treated with 2.5 mg orally weekly for 24 weeks. Stifle joints were harvested and scanned using a high-resolution micro-CT to evaluate the subchondral plate and trabecular bone changes. The macroscopic evaluation and histological analysis were determined using an adapted Osteoarthritis Research Society International scoring scheme to assess the cartilage degeneration. The lateral and medial femoral condyle and tibial plateau were evaluated. Additionally, the histological synovial membrane assessment was carried out. Sample analysis showed that the experimental model induced osteoarthritic changes in the operated joints, whereas in sham-operated rabbits, almost no histological changes were observed on articular cartilage surfaces. In terms of macroscopic and histological analyses, risedronate-treated animals did not show improved cartilage health compared with untreated operated rabbits, but a slightly anti-inflammatory activity was observed in the synovial membrane. Risedronate administration showed a slight tendency to increase subchondral bone plate thickness in lateral compartments but, it did not show conservation of periarticular bone and was not be able to suppress the osteophyte formation. In conclusion, long-term risedronate use did not demonstrate a positive effect on reducing the cartilage damage, and failed to prevent the subchondral bone changes and osteophytogenesis in an experimental rabbit model of OA. Frontiers Media S.A. https://hdl.handle.net/10347/39051
spellingShingle No Effect of Long-Term Risedronate Use on Cartilage and Subchondral Bone in an Experimental Rabbit Model of Osteoarthritis
González Cantalapiedra, Antonio
Bisphosphonate
Bone
Cartilage
Osteoarthritis
Risedronate
Synovial membrane
Subchondral bone
title No Effect of Long-Term Risedronate Use on Cartilage and Subchondral Bone in an Experimental Rabbit Model of Osteoarthritis
title_full No Effect of Long-Term Risedronate Use on Cartilage and Subchondral Bone in an Experimental Rabbit Model of Osteoarthritis
title_fullStr No Effect of Long-Term Risedronate Use on Cartilage and Subchondral Bone in an Experimental Rabbit Model of Osteoarthritis
title_full_unstemmed No Effect of Long-Term Risedronate Use on Cartilage and Subchondral Bone in an Experimental Rabbit Model of Osteoarthritis
title_short No Effect of Long-Term Risedronate Use on Cartilage and Subchondral Bone in an Experimental Rabbit Model of Osteoarthritis
title_sort No Effect of Long-Term Risedronate Use on Cartilage and Subchondral Bone in an Experimental Rabbit Model of Osteoarthritis
topic Bisphosphonate
Bone
Cartilage
Osteoarthritis
Risedronate
Synovial membrane
Subchondral bone
topic_facet Bisphosphonate
Bone
Cartilage
Osteoarthritis
Risedronate
Synovial membrane
Subchondral bone
url https://hdl.handle.net/10347/39051