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Statin treatment increases the clinical risk of tendinopathy through matrix metalloproteinase release – a cohort study design combined with an experimental study

Recent experimental evidence indicates potential adverse effects of statin treatment on tendons but previous clinical studies are few and inconclusive. The aims of our study were, first, to determine whether statin use in a cohort design is associated with tendinopathy disorders, and second, to expe...

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Autores principales: Eliasson, Pernilla, Dietrich-Zagonel, Franciele, Lundin, Anna-Carin, Aspenberg, Per, Wolk, Alicja, Michaëlsson, Karl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884518/
https://www.ncbi.nlm.nih.gov/pubmed/31784541
http://dx.doi.org/10.1038/s41598-019-53238-7
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author Eliasson, Pernilla
Dietrich-Zagonel, Franciele
Lundin, Anna-Carin
Aspenberg, Per
Wolk, Alicja
Michaëlsson, Karl
author_facet Eliasson, Pernilla
Dietrich-Zagonel, Franciele
Lundin, Anna-Carin
Aspenberg, Per
Wolk, Alicja
Michaëlsson, Karl
author_sort Eliasson, Pernilla
collection PubMed
description Recent experimental evidence indicates potential adverse effects of statin treatment on tendons but previous clinical studies are few and inconclusive. The aims of our study were, first, to determine whether statin use in a cohort design is associated with tendinopathy disorders, and second, to experimentally understand the pathogenesis of statin induced tendinopathy. We studied association between statin use and different tendon injuries in two population-based Swedish cohorts by time-dependent Cox regression analysis. Additionally, we tested simvastatin in a 3D cell culture model with human tenocytes. Compared with never-users, current users of statins had a higher incidence of trigger finger with adjusted hazard ratios (aHRs) of 1.50 for men (95% confidence interval [CI] 1.21–1.85) and 1.21 (1.02–1.43) for women. We also found a higher incidence of shoulder tendinopathy in both men (aHR 1.43; 1.24–1.65) and women (aHR 1.41; 0.97–2.05). Former users did not confer a higher risk of tendinopathies. In vitro experiments revealed an increased release of matrix metalloproteinase (MMP)-1 and MMP-13 and a weaker, disrupted matrix after simvastatin exposure. Current statin use seems to increase the risk of trigger finger and shoulder tendinopathy, possibly through increased MMP release, and subsequently, a weakened tendon matrix which will be more prone to injuries.
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spelling pubmed-68845182019-12-06 Statin treatment increases the clinical risk of tendinopathy through matrix metalloproteinase release – a cohort study design combined with an experimental study Eliasson, Pernilla Dietrich-Zagonel, Franciele Lundin, Anna-Carin Aspenberg, Per Wolk, Alicja Michaëlsson, Karl Sci Rep Article Recent experimental evidence indicates potential adverse effects of statin treatment on tendons but previous clinical studies are few and inconclusive. The aims of our study were, first, to determine whether statin use in a cohort design is associated with tendinopathy disorders, and second, to experimentally understand the pathogenesis of statin induced tendinopathy. We studied association between statin use and different tendon injuries in two population-based Swedish cohorts by time-dependent Cox regression analysis. Additionally, we tested simvastatin in a 3D cell culture model with human tenocytes. Compared with never-users, current users of statins had a higher incidence of trigger finger with adjusted hazard ratios (aHRs) of 1.50 for men (95% confidence interval [CI] 1.21–1.85) and 1.21 (1.02–1.43) for women. We also found a higher incidence of shoulder tendinopathy in both men (aHR 1.43; 1.24–1.65) and women (aHR 1.41; 0.97–2.05). Former users did not confer a higher risk of tendinopathies. In vitro experiments revealed an increased release of matrix metalloproteinase (MMP)-1 and MMP-13 and a weaker, disrupted matrix after simvastatin exposure. Current statin use seems to increase the risk of trigger finger and shoulder tendinopathy, possibly through increased MMP release, and subsequently, a weakened tendon matrix which will be more prone to injuries. Nature Publishing Group UK 2019-11-29 /pmc/articles/PMC6884518/ /pubmed/31784541 http://dx.doi.org/10.1038/s41598-019-53238-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Eliasson, Pernilla
Dietrich-Zagonel, Franciele
Lundin, Anna-Carin
Aspenberg, Per
Wolk, Alicja
Michaëlsson, Karl
Statin treatment increases the clinical risk of tendinopathy through matrix metalloproteinase release – a cohort study design combined with an experimental study
title Statin treatment increases the clinical risk of tendinopathy through matrix metalloproteinase release – a cohort study design combined with an experimental study
title_full Statin treatment increases the clinical risk of tendinopathy through matrix metalloproteinase release – a cohort study design combined with an experimental study
title_fullStr Statin treatment increases the clinical risk of tendinopathy through matrix metalloproteinase release – a cohort study design combined with an experimental study
title_full_unstemmed Statin treatment increases the clinical risk of tendinopathy through matrix metalloproteinase release – a cohort study design combined with an experimental study
title_short Statin treatment increases the clinical risk of tendinopathy through matrix metalloproteinase release – a cohort study design combined with an experimental study
title_sort statin treatment increases the clinical risk of tendinopathy through matrix metalloproteinase release – a cohort study design combined with an experimental study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884518/
https://www.ncbi.nlm.nih.gov/pubmed/31784541
http://dx.doi.org/10.1038/s41598-019-53238-7
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