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

S.L. Brennan-Olsen, R.S. Page, M. Berk, J.A. Riancho, W.D. Leslie, Scott Wilson, K.L. Saban, L. Janusek, J.A. Pasco, J.M. Hodge, S.E. Quirk, N.K. Hyde, S.M. Hosking, L.J. Williams

    Research output: Contribution to journalLiterature review

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    Abstract

    © 2015 Elsevier Inc. 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.
    Original languageEnglish
    Pages (from-to)204-212
    Number of pages9
    JournalBone
    Volume84
    Early online date23 Dec 2015
    DOIs
    Publication statusPublished - Mar 2016

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    Osteoporotic Fractures
    DNA Methylation
    Epigenomics
    Osteoporosis
    Vulnerable Populations
    Allostasis
    Social Environment
    Life Style
    Oxidative Stress
    Exercise
    Inflammation
    Gene Expression
    Bone and Bones
    Health
    Population

    Cite this

    Brennan-Olsen, S. L., Page, R. S., Berk, M., Riancho, J. A., Leslie, W. D., Wilson, S., ... Williams, L. J. (2016). DNA methylation and the social gradient of osteoporotic fracture: A conceptual model. Bone, 84, 204-212. https://doi.org/10.1016/j.bone.2015.12.015
    Brennan-Olsen, S.L. ; Page, R.S. ; Berk, M. ; Riancho, J.A. ; Leslie, W.D. ; Wilson, Scott ; Saban, K.L. ; Janusek, L. ; Pasco, J.A. ; Hodge, J.M. ; Quirk, S.E. ; Hyde, N.K. ; Hosking, S.M. ; Williams, L.J. / DNA methylation and the social gradient of osteoporotic fracture: A conceptual model. In: Bone. 2016 ; Vol. 84. pp. 204-212.
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    title = "DNA methylation and the social gradient of osteoporotic fracture: A conceptual model",
    abstract = "{\circledC} 2015 Elsevier Inc. 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.",
    author = "S.L. Brennan-Olsen and R.S. Page and M. Berk and J.A. Riancho and W.D. Leslie and Scott Wilson and K.L. Saban and L. Janusek and J.A. Pasco and J.M. Hodge and S.E. Quirk and N.K. Hyde and S.M. Hosking and L.J. Williams",
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    Brennan-Olsen, SL, Page, RS, Berk, M, Riancho, JA, Leslie, WD, Wilson, S, Saban, KL, Janusek, L, Pasco, JA, Hodge, JM, Quirk, SE, Hyde, NK, Hosking, SM & Williams, LJ 2016, 'DNA methylation and the social gradient of osteoporotic fracture: A conceptual model' Bone, vol. 84, pp. 204-212. https://doi.org/10.1016/j.bone.2015.12.015

    DNA methylation and the social gradient of osteoporotic fracture: A conceptual model. / Brennan-Olsen, S.L.; Page, R.S.; Berk, M.; Riancho, J.A.; Leslie, W.D.; Wilson, Scott; Saban, K.L.; Janusek, L.; Pasco, J.A.; Hodge, J.M.; Quirk, S.E.; Hyde, N.K.; Hosking, S.M.; Williams, L.J.

    In: Bone, Vol. 84, 03.2016, p. 204-212.

    Research output: Contribution to journalLiterature review

    TY - JOUR

    T1 - DNA methylation and the social gradient of osteoporotic fracture: A conceptual model

    AU - Brennan-Olsen, S.L.

    AU - Page, R.S.

    AU - Berk, M.

    AU - Riancho, J.A.

    AU - Leslie, W.D.

    AU - Wilson, Scott

    AU - Saban, K.L.

    AU - Janusek, L.

    AU - Pasco, J.A.

    AU - Hodge, J.M.

    AU - Quirk, S.E.

    AU - Hyde, N.K.

    AU - Hosking, S.M.

    AU - Williams, L.J.

    PY - 2016/3

    Y1 - 2016/3

    N2 - © 2015 Elsevier Inc. 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.

    AB - © 2015 Elsevier Inc. 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.

    U2 - 10.1016/j.bone.2015.12.015

    DO - 10.1016/j.bone.2015.12.015

    M3 - Literature review

    VL - 84

    SP - 204

    EP - 212

    JO - Bone

    JF - Bone

    SN - 8756-3282

    ER -