Disuse Osteoporosis: Clinical and Mechanistic Insights.
Bone loss
Immobilization
Microstructure
Osteocyte
Unloading
Journal
Calcified tissue international
ISSN: 1432-0827
Titre abrégé: Calcif Tissue Int
Pays: United States
ID NLM: 7905481
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
30
11
2020
accepted:
05
03
2021
pubmed:
20
3
2021
medline:
20
4
2022
entrez:
19
3
2021
Statut:
ppublish
Résumé
Disuse osteoporosis describes a state of bone loss due to local skeletal unloading or systemic immobilization. This review will discuss advances in the field that have shed light on clinical observations, mechanistic insights and options for the treatment of disuse osteoporosis. Clinical settings of disuse osteoporosis include spinal cord injury, other neurological and neuromuscular disorders, immobilization after fractures and bed rest (real or modeled). Furthermore, spaceflight-induced bone loss represents a well-known adaptive process to microgravity. Clinical studies have outlined that immobilization leads to immediate bone loss in both the trabecular and cortical compartments accompanied by relatively increased bone resorption and decreased bone formation. The fact that the low bone formation state has been linked to high levels of the osteocyte-secreted protein sclerostin is one of the many findings that has brought matrix-embedded, mechanosensitive osteocytes into focus in the search for mechanistic principles. Previous basic research has primarily involved rodent models based on tail suspension, spaceflight and other immobilization methods, which have underlined the importance of osteocytes in the pathogenesis of disuse osteoporosis. Furthermore, molecular-based in vitro and in vivo approaches have revealed that osteocytes sense mechanical loading through mechanosensors that translate extracellular mechanical signals to intracellular biochemical signals and regulate gene expression. Osteocytic mechanosensors include the osteocyte cytoskeleton and dendritic processes within the lacuno-canalicular system (LCS), ion channels (e.g., Piezo1), extracellular matrix, primary cilia, focal adhesions (integrin-based) and hemichannels and gap junctions (connexin-based). Overall, disuse represents one of the major factors contributing to immediate bone loss and osteoporosis, and alterations in osteocytic pathways appear crucial to the bone loss associated with unloading.
Identifiants
pubmed: 33738515
doi: 10.1007/s00223-021-00836-1
pii: 10.1007/s00223-021-00836-1
pmc: PMC9013332
doi:
Substances chimiques
Ion Channels
0
PIEZO1 protein, human
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
592-604Informations de copyright
© 2021. The Author(s).
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