Pathogenesis of osteoporosis: the role of estrogen
DOI:
https://doi.org/10.18597/rcog.477Keywords:
menopause, osteoporosis, estrogen, pathogenesisAbstract
Introduction: osteoporosis is a disorder in which loss of bone strength leads to fragility fractures. Hip fractures have very high morbidity and mortality and there are similar findings regarding vertebral fractures. This disorder’s increasing prevalence and tremendous costs underscore the importance of developing new treatment. Identifying the molecular mechanisms controlling bone mass has thus become a priority task.
Bone resorption by osteoclasts is coupled to bone formation by osteoblasts, such balanced process continuously remodelling and adapting the skeleton. Bone fragility results from failed adaptation.
Bone remodelling becomes unbalanced at menopause and results in bone loss.
Oestrogen deficiency leads to an overall increase in IL-7 production, partly through decreased TGF-ß and increased IGF-1. This leads to T-cell activation. Activated T-cells release IFN-g, thereby increasing antigen presentation. Oestrogen deficiency also amplifies T-cell activation and osteoclastogenesis by down-regulating antioxidant pathways. The resulting increase in oxidants stimulates antigen presentation and TNF production by mature osteoclasts. The combined effect of IFN-g and oxidants promotes RANKL and TNF osteoclastogenic factor release.
TNF stimulates stem cells and RANKL and M-CSF osteoblast production, driving osteoclast formation. TNF and IL-7 blunt bone formation through direct repressive effects on osteoblasts.
Author Biographies
Oswaldo Rincón-Sierra
Ivonne Díaz-Yamal
Luis Ernesto Pérez-Agudelo
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