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Impact of Early Conventional Treatment on Adult Bone and Joints in a Murine Model of X-Linked Hypophosphatemia
X-linked hypophosphatemia (XLH) is the most common form of genetic rickets. Mainly diagnosed during childhood because of growth retardation and deformities of the lower limbs, the disease affects adults with early enthesopathies and joint structural damage that significantly alter patient quality of...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930336/ https://www.ncbi.nlm.nih.gov/pubmed/33681179 http://dx.doi.org/10.3389/fcell.2020.591417 |
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author | Cauliez, Axelle Zhukouskaya, Volha V. Hilliquin, Stéphane Sadoine, Jérémy Slimani, Lotfi Miceli-Richard, Corinne Briot, Karine Linglart, Agnès Chaussain, Catherine Bardet, Claire |
author_facet | Cauliez, Axelle Zhukouskaya, Volha V. Hilliquin, Stéphane Sadoine, Jérémy Slimani, Lotfi Miceli-Richard, Corinne Briot, Karine Linglart, Agnès Chaussain, Catherine Bardet, Claire |
author_sort | Cauliez, Axelle |
collection | PubMed |
description | X-linked hypophosphatemia (XLH) is the most common form of genetic rickets. Mainly diagnosed during childhood because of growth retardation and deformities of the lower limbs, the disease affects adults with early enthesopathies and joint structural damage that significantly alter patient quality of life. The conventional treatment, based on phosphorus supplementation and active vitamin D analogs, is commonly administered from early childhood to the end of growth; unfortunately, it does not allow complete recovery from skeletal damage. Despite adequate treatment during childhood, bone and joint complications occur in adults and become a dominant feature in the natural history of the disease. Our previous data showed that the Hyp mouse is a relevant model of XLH for studying early enthesophytes and joint structural damage. Here, we studied the effect of conventional treatment on the development of bone and joint alterations in this mouse model during growth and young adulthood. Mice were supplemented with oral phosphorus and calcitriol injections, following two timelines: (i) from weaning to 3 months of age and (ii) from 2 to 3 months to evaluate the effects of treatment on the development of early enthesophytes and joint alterations, and on changes in bone and joint deformities already present, respectively. We showed that early conventional treatment improved bone microarchitecture, and partially prevented bone and joint complications, but with no noticeable improvement in enthesophytes. In contrast, later administration had limited efficacy in ameliorating bone and joint alterations. Despite the improvement in bone microarchitecture, the conventional treatment, early or late, had no effect on osteoid accumulation. Our data underline the usefulness of the Hyp murine model for preclinical studies on skeletal and extraskeletal lesions. Although the early conventional treatment is important for the improvement of bone microarchitecture, the persistence of osteomalacia implies seeking new therapeutic strategies, in particular anti-FGF23 approach, in order to optimize the treatment of XLH. |
format | Online Article Text |
id | pubmed-7930336 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79303362021-03-05 Impact of Early Conventional Treatment on Adult Bone and Joints in a Murine Model of X-Linked Hypophosphatemia Cauliez, Axelle Zhukouskaya, Volha V. Hilliquin, Stéphane Sadoine, Jérémy Slimani, Lotfi Miceli-Richard, Corinne Briot, Karine Linglart, Agnès Chaussain, Catherine Bardet, Claire Front Cell Dev Biol Cell and Developmental Biology X-linked hypophosphatemia (XLH) is the most common form of genetic rickets. Mainly diagnosed during childhood because of growth retardation and deformities of the lower limbs, the disease affects adults with early enthesopathies and joint structural damage that significantly alter patient quality of life. The conventional treatment, based on phosphorus supplementation and active vitamin D analogs, is commonly administered from early childhood to the end of growth; unfortunately, it does not allow complete recovery from skeletal damage. Despite adequate treatment during childhood, bone and joint complications occur in adults and become a dominant feature in the natural history of the disease. Our previous data showed that the Hyp mouse is a relevant model of XLH for studying early enthesophytes and joint structural damage. Here, we studied the effect of conventional treatment on the development of bone and joint alterations in this mouse model during growth and young adulthood. Mice were supplemented with oral phosphorus and calcitriol injections, following two timelines: (i) from weaning to 3 months of age and (ii) from 2 to 3 months to evaluate the effects of treatment on the development of early enthesophytes and joint alterations, and on changes in bone and joint deformities already present, respectively. We showed that early conventional treatment improved bone microarchitecture, and partially prevented bone and joint complications, but with no noticeable improvement in enthesophytes. In contrast, later administration had limited efficacy in ameliorating bone and joint alterations. Despite the improvement in bone microarchitecture, the conventional treatment, early or late, had no effect on osteoid accumulation. Our data underline the usefulness of the Hyp murine model for preclinical studies on skeletal and extraskeletal lesions. Although the early conventional treatment is important for the improvement of bone microarchitecture, the persistence of osteomalacia implies seeking new therapeutic strategies, in particular anti-FGF23 approach, in order to optimize the treatment of XLH. Frontiers Media S.A. 2021-02-18 /pmc/articles/PMC7930336/ /pubmed/33681179 http://dx.doi.org/10.3389/fcell.2020.591417 Text en Copyright © 2021 Cauliez, Zhukouskaya, Hilliquin, Sadoine, Slimani, Miceli-Richard, Briot, Linglart, Chaussain and Bardet. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Cauliez, Axelle Zhukouskaya, Volha V. Hilliquin, Stéphane Sadoine, Jérémy Slimani, Lotfi Miceli-Richard, Corinne Briot, Karine Linglart, Agnès Chaussain, Catherine Bardet, Claire Impact of Early Conventional Treatment on Adult Bone and Joints in a Murine Model of X-Linked Hypophosphatemia |
title | Impact of Early Conventional Treatment on Adult Bone and Joints in a Murine Model of X-Linked Hypophosphatemia |
title_full | Impact of Early Conventional Treatment on Adult Bone and Joints in a Murine Model of X-Linked Hypophosphatemia |
title_fullStr | Impact of Early Conventional Treatment on Adult Bone and Joints in a Murine Model of X-Linked Hypophosphatemia |
title_full_unstemmed | Impact of Early Conventional Treatment on Adult Bone and Joints in a Murine Model of X-Linked Hypophosphatemia |
title_short | Impact of Early Conventional Treatment on Adult Bone and Joints in a Murine Model of X-Linked Hypophosphatemia |
title_sort | impact of early conventional treatment on adult bone and joints in a murine model of x-linked hypophosphatemia |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930336/ https://www.ncbi.nlm.nih.gov/pubmed/33681179 http://dx.doi.org/10.3389/fcell.2020.591417 |
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