DNA methylation and the social gradient of osteoporotic fracture: a conceptual model

Brennan-Olsen, Sharon L., Page, Richard S., Berk, Michael, Riancho, José A., Leslie, William D., Wilson, Scott G., Saban, Karen L., Janusek, Linda, Pasco, Julie A., Hodge, Jason M., Quirk, Shae E., Hyde, Natalie K., Hosking, Sarah M. and Williams, Lana J. 2016, DNA methylation and the social gradient of osteoporotic fracture: a conceptual model, Bone, vol. 84, pp. 204-212, doi: 10.1016/j.bone.2015.12.015.

Attached Files
Name Description MIMEType Size Downloads

Title DNA methylation and the social gradient of osteoporotic fracture: a conceptual model
Author(s) Brennan-Olsen, Sharon L.
Page, Richard S.ORCID iD for Page, Richard S. orcid.org/0000-0002-2225-7144
Berk, MichaelORCID iD for Berk, Michael orcid.org/0000-0002-5554-6946
Riancho, José A.
Leslie, William D.
Wilson, Scott G.
Saban, Karen L.
Janusek, Linda
Pasco, Julie A.ORCID iD for Pasco, Julie A. orcid.org/0000-0002-8968-4714
Hodge, Jason M.
Quirk, Shae E.
Hyde, Natalie K.
Hosking, Sarah M.
Williams, Lana J.ORCID iD for Williams, Lana J. orcid.org/0000-0002-1377-1272
Journal name Bone
Volume number 84
Start page 204
End page 212
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2016-03
ISSN 1873-2763
Keyword(s) DNA methylation
epigenetic
fracture
life course
osteoporosis
social gradient
Summary 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. MINI ABSTRACT: Our conceptual model proposes how DNA methylation might underpin the social gradient in osteoporotic fracture. We suggest that social disadvantage is associated with priming of inflammatory signalling pathways, which is mediated by epigenetic modifications, leading to a chronically heightened inflammatory state that places disadvantaged individuals at greater risk of osteoporosis.
Language eng
DOI 10.1016/j.bone.2015.12.015
Field of Research 11 Medical And Health Sciences
06 Biological Sciences
09 Engineering
110399 Clinical Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Elsevier
Persistent URL http://hdl.handle.net/10536/DRO/DU:30080737

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 4 times in TR Web of Science
Scopus Citation Count Cited 7 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 255 Abstract Views, 2 File Downloads  -  Detailed Statistics
Created: Fri, 15 Jan 2016, 08:45:51 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.