Potential influences on optimizing long-term musculoskeletal health in children and adolescents with X-linked hypophosphatemia (XLH)
Potential influences on optimizing long-term musculoskeletal health in children and adolescents with X-linked hypophosphatemia (XLH)
In recent years, much progress has been made in understanding the mechanisms of bone growth and development over a lifespan, including the crosstalk between muscle and bone, to achieve optimal structure and function. While there have been significant advances in understanding how to help improve and maintain bone health in normal individuals, there is limited knowledge on whether these mechanisms apply or are compromised in pathological states. X-linked hypophosphatemia (XLH) (ORPHA:89936) is a rare, heritable, renal phosphate-wasting disorder. The resultant chronic hypophosphatemia leads to progressive deterioration in musculoskeletal function, including impaired growth, rickets, and limb deformities in children, as well as lifelong osteomalacia with reduced bone quality and impaired muscle structure and function. The clinical manifestations of the disease vary both in presentation and severity in affected individuals, and many of the consequences of childhood defects persist into adulthood, causing significant morbidity that impacts physical function and quality of life. Intervention to restore phosphate levels early in life during the critical stages of skeletal development in children with XLH could optimize growth and may prevent or reduce bone deformities in childhood. A healthier bone structure, together with improved muscle function, can lead to physical activity enhancing musculoskeletal health throughout life. In adults, continued management may help to maintain the positive effects acquired from childhood treatment, thereby slowing or halting disease progression. In this review, we summarize the opinions from members of a working group with expertise in pediatrics, epidemiology, and bone, joint and muscle biology, on potential outcomes for people with XLH, who have been optimally treated from an early age and continue treatment throughout life.
Bone mineralization, FGF23, Long-term outcomes, Musculoskeletal health, Phosphate homeostasis, X-linked hypophosphatemia
Glorieux, Francis H.
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Bonewald, Lynda F.
e16f4d2b-da6f-40e6-a942-93a668f26a8e
Harvey, Nicholas
ce487fb4-d360-4aac-9d17-9466d6cba145
van der Meulen, Marjolein C H
569339de-e7da-44b7-b62e-6aa1d4214f42
31 January 2022
Glorieux, Francis H.
9925679c-01af-4472-8f4f-f32a591d2a8a
Bonewald, Lynda F.
e16f4d2b-da6f-40e6-a942-93a668f26a8e
Harvey, Nicholas
ce487fb4-d360-4aac-9d17-9466d6cba145
van der Meulen, Marjolein C H
569339de-e7da-44b7-b62e-6aa1d4214f42
Glorieux, Francis H., Bonewald, Lynda F., Harvey, Nicholas and van der Meulen, Marjolein C H
(2022)
Potential influences on optimizing long-term musculoskeletal health in children and adolescents with X-linked hypophosphatemia (XLH).
Orphanet Journal of Rare Diseases, 17 (30), [30].
(doi:10.1186/s13023-021-02156-x).
Abstract
In recent years, much progress has been made in understanding the mechanisms of bone growth and development over a lifespan, including the crosstalk between muscle and bone, to achieve optimal structure and function. While there have been significant advances in understanding how to help improve and maintain bone health in normal individuals, there is limited knowledge on whether these mechanisms apply or are compromised in pathological states. X-linked hypophosphatemia (XLH) (ORPHA:89936) is a rare, heritable, renal phosphate-wasting disorder. The resultant chronic hypophosphatemia leads to progressive deterioration in musculoskeletal function, including impaired growth, rickets, and limb deformities in children, as well as lifelong osteomalacia with reduced bone quality and impaired muscle structure and function. The clinical manifestations of the disease vary both in presentation and severity in affected individuals, and many of the consequences of childhood defects persist into adulthood, causing significant morbidity that impacts physical function and quality of life. Intervention to restore phosphate levels early in life during the critical stages of skeletal development in children with XLH could optimize growth and may prevent or reduce bone deformities in childhood. A healthier bone structure, together with improved muscle function, can lead to physical activity enhancing musculoskeletal health throughout life. In adults, continued management may help to maintain the positive effects acquired from childhood treatment, thereby slowing or halting disease progression. In this review, we summarize the opinions from members of a working group with expertise in pediatrics, epidemiology, and bone, joint and muscle biology, on potential outcomes for people with XLH, who have been optimally treated from an early age and continue treatment throughout life.
Text
s13023-021-02156-x
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Accepted/In Press date: 19 December 2021
Published date: 31 January 2022
Additional Information:
Funding Information:
We would like to thank Sciterion for the medical writing support provided and funded by Kyowa Kirin International.
Publisher Copyright:
© 2022, The Author(s).
Keywords:
Bone mineralization, FGF23, Long-term outcomes, Musculoskeletal health, Phosphate homeostasis, X-linked hypophosphatemia
Identifiers
Local EPrints ID: 454776
URI: http://eprints.soton.ac.uk/id/eprint/454776
ISSN: 1750-1172
PURE UUID: d5189ff1-5007-4f83-bdc8-c0d90efed060
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Date deposited: 23 Feb 2022 17:35
Last modified: 17 Mar 2024 02:58
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Author:
Francis H. Glorieux
Author:
Lynda F. Bonewald
Author:
Marjolein C H van der Meulen
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