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Mechanisms of Bone Fragility: From Osteogenesis Imperfecta to Secondary Osteoporosis

Bone material strength is determined by several factors, such as bone mass, matrix composition, mineralization, architecture and shape. From a clinical perspective, bone fragility is classified as primary (i.e., genetic and rare) or secondary (i.e., acquired and common) osteoporosis. Understanding t...

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Detalles Bibliográficos
Autores principales: El-Gazzar, Ahmed, Högler, Wolfgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826666/
https://www.ncbi.nlm.nih.gov/pubmed/33435159
http://dx.doi.org/10.3390/ijms22020625
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author El-Gazzar, Ahmed
Högler, Wolfgang
author_facet El-Gazzar, Ahmed
Högler, Wolfgang
author_sort El-Gazzar, Ahmed
collection PubMed
description Bone material strength is determined by several factors, such as bone mass, matrix composition, mineralization, architecture and shape. From a clinical perspective, bone fragility is classified as primary (i.e., genetic and rare) or secondary (i.e., acquired and common) osteoporosis. Understanding the mechanism of rare genetic bone fragility disorders not only advances medical knowledge on rare diseases, it may open doors for drug development for more common disorders (i.e., postmenopausal osteoporosis). In this review, we highlight the main disease mechanisms underlying the development of human bone fragility associated with low bone mass known to date. The pathways we focus on are type I collagen processing, WNT-signaling, TGF-ß signaling, the RANKL-RANK system and the osteocyte mechanosensing pathway. We demonstrate how the discovery of most of these pathways has led to targeted, pathway-specific treatments.
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spelling pubmed-78266662021-01-25 Mechanisms of Bone Fragility: From Osteogenesis Imperfecta to Secondary Osteoporosis El-Gazzar, Ahmed Högler, Wolfgang Int J Mol Sci Review Bone material strength is determined by several factors, such as bone mass, matrix composition, mineralization, architecture and shape. From a clinical perspective, bone fragility is classified as primary (i.e., genetic and rare) or secondary (i.e., acquired and common) osteoporosis. Understanding the mechanism of rare genetic bone fragility disorders not only advances medical knowledge on rare diseases, it may open doors for drug development for more common disorders (i.e., postmenopausal osteoporosis). In this review, we highlight the main disease mechanisms underlying the development of human bone fragility associated with low bone mass known to date. The pathways we focus on are type I collagen processing, WNT-signaling, TGF-ß signaling, the RANKL-RANK system and the osteocyte mechanosensing pathway. We demonstrate how the discovery of most of these pathways has led to targeted, pathway-specific treatments. MDPI 2021-01-10 /pmc/articles/PMC7826666/ /pubmed/33435159 http://dx.doi.org/10.3390/ijms22020625 Text en © 2021 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
El-Gazzar, Ahmed
Högler, Wolfgang
Mechanisms of Bone Fragility: From Osteogenesis Imperfecta to Secondary Osteoporosis
title Mechanisms of Bone Fragility: From Osteogenesis Imperfecta to Secondary Osteoporosis
title_full Mechanisms of Bone Fragility: From Osteogenesis Imperfecta to Secondary Osteoporosis
title_fullStr Mechanisms of Bone Fragility: From Osteogenesis Imperfecta to Secondary Osteoporosis
title_full_unstemmed Mechanisms of Bone Fragility: From Osteogenesis Imperfecta to Secondary Osteoporosis
title_short Mechanisms of Bone Fragility: From Osteogenesis Imperfecta to Secondary Osteoporosis
title_sort mechanisms of bone fragility: from osteogenesis imperfecta to secondary osteoporosis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826666/
https://www.ncbi.nlm.nih.gov/pubmed/33435159
http://dx.doi.org/10.3390/ijms22020625
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