Cargando…

Myeloma Bone Disease: The Osteoblast in the Spotlight

Lytic bone disease remains a life-altering complication of multiple myeloma, with up to 90% of sufferers experiencing skeletal events at some point in their cancer journey. This tumour-induced bone disease is driven by an upregulation of bone resorption (via increased osteoclast (OC) activity) and a...

Descripción completa

Detalles Bibliográficos
Autores principales: Andrews, Rebecca E., Brown, Janet E., Lawson, Michelle A., Chantry, Andrew D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432062/
https://www.ncbi.nlm.nih.gov/pubmed/34501423
http://dx.doi.org/10.3390/jcm10173973
_version_ 1783751076578590720
author Andrews, Rebecca E.
Brown, Janet E.
Lawson, Michelle A.
Chantry, Andrew D.
author_facet Andrews, Rebecca E.
Brown, Janet E.
Lawson, Michelle A.
Chantry, Andrew D.
author_sort Andrews, Rebecca E.
collection PubMed
description Lytic bone disease remains a life-altering complication of multiple myeloma, with up to 90% of sufferers experiencing skeletal events at some point in their cancer journey. This tumour-induced bone disease is driven by an upregulation of bone resorption (via increased osteoclast (OC) activity) and a downregulation of bone formation (via reduced osteoblast (OB) activity), leading to phenotypic osteolysis. Treatments are limited, and currently exclusively target OCs. Despite existing bone targeting therapies, patients successfully achieving remission from their cancer can still be left with chronic pain, poor mobility, and reduced quality of life as a result of bone disease. As such, the field is desperately in need of new and improved bone-modulating therapeutic agents. One such option is the use of bone anabolics, drugs that are gaining traction in the osteoporosis field following successful clinical trials. The prospect of using these therapies in relation to myeloma is an attractive option, as they aim to stimulate OBs, as opposed to existing therapeutics that do little to orchestrate new bone formation. The preclinical application of bone anabolics in myeloma mouse models has demonstrated positive outcomes for bone repair and fracture resistance. Here, we review the role of the OB in the pathophysiology of myeloma-induced bone disease and explore whether novel OB targeted therapies could improve outcomes for patients.
format Online
Article
Text
id pubmed-8432062
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-84320622021-09-11 Myeloma Bone Disease: The Osteoblast in the Spotlight Andrews, Rebecca E. Brown, Janet E. Lawson, Michelle A. Chantry, Andrew D. J Clin Med Review Lytic bone disease remains a life-altering complication of multiple myeloma, with up to 90% of sufferers experiencing skeletal events at some point in their cancer journey. This tumour-induced bone disease is driven by an upregulation of bone resorption (via increased osteoclast (OC) activity) and a downregulation of bone formation (via reduced osteoblast (OB) activity), leading to phenotypic osteolysis. Treatments are limited, and currently exclusively target OCs. Despite existing bone targeting therapies, patients successfully achieving remission from their cancer can still be left with chronic pain, poor mobility, and reduced quality of life as a result of bone disease. As such, the field is desperately in need of new and improved bone-modulating therapeutic agents. One such option is the use of bone anabolics, drugs that are gaining traction in the osteoporosis field following successful clinical trials. The prospect of using these therapies in relation to myeloma is an attractive option, as they aim to stimulate OBs, as opposed to existing therapeutics that do little to orchestrate new bone formation. The preclinical application of bone anabolics in myeloma mouse models has demonstrated positive outcomes for bone repair and fracture resistance. Here, we review the role of the OB in the pathophysiology of myeloma-induced bone disease and explore whether novel OB targeted therapies could improve outcomes for patients. MDPI 2021-09-02 /pmc/articles/PMC8432062/ /pubmed/34501423 http://dx.doi.org/10.3390/jcm10173973 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Andrews, Rebecca E.
Brown, Janet E.
Lawson, Michelle A.
Chantry, Andrew D.
Myeloma Bone Disease: The Osteoblast in the Spotlight
title Myeloma Bone Disease: The Osteoblast in the Spotlight
title_full Myeloma Bone Disease: The Osteoblast in the Spotlight
title_fullStr Myeloma Bone Disease: The Osteoblast in the Spotlight
title_full_unstemmed Myeloma Bone Disease: The Osteoblast in the Spotlight
title_short Myeloma Bone Disease: The Osteoblast in the Spotlight
title_sort myeloma bone disease: the osteoblast in the spotlight
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432062/
https://www.ncbi.nlm.nih.gov/pubmed/34501423
http://dx.doi.org/10.3390/jcm10173973
work_keys_str_mv AT andrewsrebeccae myelomabonediseasetheosteoblastinthespotlight
AT brownjanete myelomabonediseasetheosteoblastinthespotlight
AT lawsonmichellea myelomabonediseasetheosteoblastinthespotlight
AT chantryandrewd myelomabonediseasetheosteoblastinthespotlight