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DNA methylation and the social gradient of osteoporotic fracture: A conceptual model
Brennan-Olsen, Sharon L. Page, Richard S. Berk, Michael Riancho, Jose A. Leslie, William D. Wilson, Scott G. Saban, Karen L. Janusek, Linda Pasco, Julie A. Hodge, Jason M.
Brennan-Olsen, Sharon L.
Page, Richard S.
Berk, Michael
Riancho, Jose A.
Leslie, William D.
Wilson, Scott G.
Saban, Karen L.
Janusek, Linda
Pasco, Julie A.
Hodge, Jason M.
Abstract
Introduction: Although there is a documented social gradient for osteoporosis, the underlying mechanism(s) for that gradient remain unknown. We propose a conceptual model based upon the allostatic load theory, to suggest how DNA methylation (DNAm) might underpin the social gradient in osteoporosis and fracture. We hypothesise that social disadvantage is associated with priming of inflammatory pathways mediated by epigenetic modification that leads to an enhanced state of inflammatory reactivity and oxidative stress, and thus places socially disadvantaged individuals at greater risk of osteoporotic fracture. Methods/Results: Based on a review of the literature, we present a conceptual model in which social disadvantage increases stress throughout the lifespan, and engenders a proinflammatory epigenetic signature, leading to a heightened inflammatory state that increases risk for osteoporotic fracture in disadvantaged groups that are chronically stressed. Conclusions: Our model proposes that, in addition to the direct biological effects exerted on bone by factors such as physical activity and nutrition, the recognised socially patterned risk factors for osteoporosis also act via epigenetic-mediated dysregulation of inflammation. DNAm is a dynamic modulator of gene expression with considerable relevance to the field of osteoporosis. Elucidating the extent to which this epigenetic mechanism transduces the psycho-social environment to increase the risk of osteoporotic fracture may yield novel entry points for intervention that can be used to reduce individual and population-wide risks for osteoporotic fracture. Specifically, an epigenetic evidence-base may strengthen the importance of lifestyle modification and stress reduction programs, and help to reduce health inequities across social groups.
Keywords
DNA methylation, osteoporosis, social gradient, fracture, epigenetic, life course
Date
2016
Type
Journal article
Journal
Bone
Book
Volume
84
Issue
Page Range
204-212
Article Number
ACU Department
Collections
Relation URI
Source URL
Event URL
Open Access Status
License
File Access
Controlled