TY  - JOUR
A1  - Ehnert, Sabrina
A1  - Aspera-Werz, Romina Haydeé
A1  - Ruoß, Marc
A1  - Dooley, Steven
A1  - Hengstler, Jan Georg
A1  - Nadalin, Silvio
A1  - Relja, Borna
A1  - Badke, Andreas
A1  - Nussler, Andreas Klaus
T1  - Hepatic osteodystrophy—molecular mechanisms proposed to favor its development
T2  - International journal of molecular sciences
N2  - 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.
KW  - bone metabolism
KW  - osteopenia
KW  - osteoporosis
KW  - liver disease
KW  - hepatic osteodystrophy
KW  - vitamin Dmetabolism
KW  - transforming growth factor beta (TGF-β)
KW  - bone morphogenetic proteins (BMPs)
KW  - histone deacetylases (HDACs)
KW  - sclerostin
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/53331
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-533310
SN  - 1422-0067
SN  - 1661-6596
N1  - This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
VL  - 20
IS  - 10, Art. 2555
SP  - 1
EP  - 31
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -