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Hepatic Osteodystrophy—Molecular Mechanisms Proposed to Favor Its Development

Almost all patients with chronic liver diseases (CLD) show altered bone metabolism. Depending on the etiology, this manifests in a severe osteoporosis in up to 75% of the affected patients. Due to high prevalence, the generic term hepatic osteodystrophy (HOD) evolved, describing altered bone metabol...

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Autores principales: Ehnert, Sabrina, Aspera-Werz, Romina H., Ruoß, Marc, Dooley, Steven, Hengstler, Jan G., Nadalin, Silvio, Relja, Borna, Badke, Andreas, Nussler, Andreas K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566554/
https://www.ncbi.nlm.nih.gov/pubmed/31137669
http://dx.doi.org/10.3390/ijms20102555
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author Ehnert, Sabrina
Aspera-Werz, Romina H.
Ruoß, Marc
Dooley, Steven
Hengstler, Jan G.
Nadalin, Silvio
Relja, Borna
Badke, Andreas
Nussler, Andreas K.
author_facet Ehnert, Sabrina
Aspera-Werz, Romina H.
Ruoß, Marc
Dooley, Steven
Hengstler, Jan G.
Nadalin, Silvio
Relja, Borna
Badke, Andreas
Nussler, Andreas K.
author_sort Ehnert, Sabrina
collection PubMed
description Almost all patients with chronic liver diseases (CLD) show altered bone metabolism. Depending on the etiology, this manifests in a severe osteoporosis in up to 75% of the affected patients. Due to high prevalence, the generic term hepatic osteodystrophy (HOD) evolved, describing altered bone metabolism, decreased bone mineral density, and deterioration of bone structure in patients with CLD. Once developed, HOD is difficult to treat and increases the risk of fragility fractures. Existing fractures affect the quality of life and, more importantly, long-term prognosis of these patients, which presents with increased mortality. Thus, special care is required to support the healing process. However, for early diagnosis (reduce fracture risk) and development of adequate treatment strategies (support healing of existing fractures), it is essential to understand the underlying mechanisms that link disturbed liver function with this bone phenotype. In the present review, we summarize proposed molecular mechanisms favoring the development of HOD and compromising the healing of associated fractures, including alterations in vitamin D metabolism and action, disbalances in transforming growth factor beta (TGF-β) and bone morphogenetic protein (BMP) signaling with histone deacetylases (HDACs) as secondary regulators, as well as alterations in the receptor activator of nuclear factor kappa B ligand (RANKL)–osteoprotegerin (OPG) system mediated by sclerostin. Based on these mechanisms, we give an overview on the limitations of early diagnosis of HOD with established serum markers.
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spelling pubmed-65665542019-06-17 Hepatic Osteodystrophy—Molecular Mechanisms Proposed to Favor Its Development Ehnert, Sabrina Aspera-Werz, Romina H. Ruoß, Marc Dooley, Steven Hengstler, Jan G. Nadalin, Silvio Relja, Borna Badke, Andreas Nussler, Andreas K. Int J Mol Sci Review Almost all patients with chronic liver diseases (CLD) show altered bone metabolism. Depending on the etiology, this manifests in a severe osteoporosis in up to 75% of the affected patients. Due to high prevalence, the generic term hepatic osteodystrophy (HOD) evolved, describing altered bone metabolism, decreased bone mineral density, and deterioration of bone structure in patients with CLD. Once developed, HOD is difficult to treat and increases the risk of fragility fractures. Existing fractures affect the quality of life and, more importantly, long-term prognosis of these patients, which presents with increased mortality. Thus, special care is required to support the healing process. However, for early diagnosis (reduce fracture risk) and development of adequate treatment strategies (support healing of existing fractures), it is essential to understand the underlying mechanisms that link disturbed liver function with this bone phenotype. In the present review, we summarize proposed molecular mechanisms favoring the development of HOD and compromising the healing of associated fractures, including alterations in vitamin D metabolism and action, disbalances in transforming growth factor beta (TGF-β) and bone morphogenetic protein (BMP) signaling with histone deacetylases (HDACs) as secondary regulators, as well as alterations in the receptor activator of nuclear factor kappa B ligand (RANKL)–osteoprotegerin (OPG) system mediated by sclerostin. Based on these mechanisms, we give an overview on the limitations of early diagnosis of HOD with established serum markers. MDPI 2019-05-24 /pmc/articles/PMC6566554/ /pubmed/31137669 http://dx.doi.org/10.3390/ijms20102555 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Ehnert, Sabrina
Aspera-Werz, Romina H.
Ruoß, Marc
Dooley, Steven
Hengstler, Jan G.
Nadalin, Silvio
Relja, Borna
Badke, Andreas
Nussler, Andreas K.
Hepatic Osteodystrophy—Molecular Mechanisms Proposed to Favor Its Development
title Hepatic Osteodystrophy—Molecular Mechanisms Proposed to Favor Its Development
title_full Hepatic Osteodystrophy—Molecular Mechanisms Proposed to Favor Its Development
title_fullStr Hepatic Osteodystrophy—Molecular Mechanisms Proposed to Favor Its Development
title_full_unstemmed Hepatic Osteodystrophy—Molecular Mechanisms Proposed to Favor Its Development
title_short Hepatic Osteodystrophy—Molecular Mechanisms Proposed to Favor Its Development
title_sort hepatic osteodystrophy—molecular mechanisms proposed to favor its development
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566554/
https://www.ncbi.nlm.nih.gov/pubmed/31137669
http://dx.doi.org/10.3390/ijms20102555
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