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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6566554 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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