Natalie K. Hyde

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

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.

Musculoskeletal decline and mortality: prospective data from the Geelong Osteoporosis Study

We aimed to examine the relationship between musculoskeletal deterioration and all‐cause mortality in a cohort of women studied prospectively over a decade.

Recommendations for dietary calcium intake and bone health: the role of health literacy

Osteoporosis is a skeletal disease that involves micro-architectural deterioration of the bone matrix and depletion of bone mineral. Inadequate dietary calcium, especially in a vitamin D deficient environment, may predispose an individual to osteoporosis. Given that recommendations for daily intake (RDI) of dietary calcium differ between countries, and according to life-stages, understanding RDIs and how to achieve them is likely to be a complex process for many individuals. Health literacy, or the ability of individuals to gain access to, understand and use health-related information, will influence the capacity of individuals to meet RDIs. Furthermore, the lowest health literacy is observed in the same groups identified as having an increased risk of osteoporosis; older individuals, and those that are socially disadvantaged. It is imperative to consider the specific health literacy needs of at-risk populations when promoting recommendations for dietary calcium intake.

Low Lean Tissue Mass and Physical Performance as Markers of Sarcopenia in Older Men and Women

Background: While declines in muscle mass and function occur in all individuals with advancing age, the extent and rate of decline vary in the general population. We aimed to determine the prevalence of low lean tissue mass combined with poor physical function as an indicator of sarcopenia among older men and women residing in southeastern Australia. Methods: The study involved men and women aged 60+ years from the Geelong Osteoporosis Study (GOS). Skeletal muscle mass was measured as total lean tissue mass by dual energy x-ray absorptiometry (DXA) and expressed as a percentage of body weight to generate the skeletal mass index (SMI); low lean mass was defined as SMI T-score 10s. Physical activity scores were determined using a validated questionnaire for the elderly and falls were self-reported for the previous year. Associations between sarcopenia, physical activity and falls were determined using multivariable regression techniques. Results: Among 624 men, 233 had low SMI, 169 had low muscle performance and 81 had both, thus meeting criteria for sarcopenia. Among 436 women, 143 had low SMI, 179 had low muscle performance and 70 had both. A general age-related increase in the observed prevalence of sarcopenia appeared to be driven by an age-related increase in low performance. Sarcopenia was associated with lower physical activity scores. No association was detected between sarcopenia and falls for men but an association was observed for women (age-adjusted OR 1.87, 95% CI 1.11, 3.14). Conclusion: In our population, the prevalence of sarcopenia was 10.6% (95% CI 7.7, 13.4) for men and 14.5% (95% CI 10.8, 18.3) for women. Men and women with sarcopenia were habitually less active and, for women, sarcopenia was associated with increased likelihood of falls.

Vitamin D during pregnancy and offspring body composition: a prospective cohort study: Maternal vitamin D and child body composition

Evidence regarding the association between gestational vitamin D status and offspring body composition during childhood is inconsistent. Therefore, we aimed to determine the association between maternal vitamin D and offspring lean and fat mass in the Vitamin D in Pregnancy birth cohort.

The microbiome: a biological mechanism underpinning the social gradient of musculoskeletal conditions?

We read with interest the article by Steves et al, published in J Bone Miner Res, 2016; 31(2):261-269 (1). The authors review available evidence and suggest that the modifiable nature of the gut microbiome (GM) provides a potential therapeutic target to intervene in musculoskeletal conditions of aging.

Health literacy and uptake of dietary calcium recommendations in women

Aims: Fractures have immediate morbidity, cost, and reduce longevity; consequences that can be averted by preemptive immediate treatment provided women at risk of imminent fracture can be identified before the event. Neither bone densitometry nor FRAX assessment address this need. As increased cortical porosity and reduced trabecular density predispose to fracture, we hypothesized that measurement of microstructural deterioration will identify patients at risk of imminent fracture (within ~2 y of assessment) and will do so with greater sensitivity and specificity than BMD or FRAX. Methods: We tested this hypothesis in a prospective cohort of 589 women aged 42–94 y (OFELY cohort). Distal radius microstructure was acquired using HRpQCT (Scanco Medical, Switzerland) and processed using StrAx1.0 (StraxCorp, Melbourne, Australia). Microstructural deterioration was expressed on a continuous scale as a Structural Fragility Score which captures the increment in cortical porosity and deficit in trabecular density relative to young normal women. Femoral neck BMD was measured and FRAX major osteoporotic fractures scores calculated. Thresholds used to identify individuals at risk for imminent fractures were 22 for SFS (arbitrary unit), 20 % for FRAX, and T-score < −2.5 for BMD. Results: Of the 589 women, 33 (5.6 %) sustained a fracture within 2 y of assessment. Sensitivity and specificity were 61 and 75% for the SFS, 18 and 95% for BMD; and 22 and 90% for FRAX. In a multivariate model, the SFS predicted imminent fractures independently of BMD and FRAX. Of the 33 imminent fractures, 19 were identified by SFS which also captured the 6 and 7 identified by BMD and FRAX, respectively. Conclusion: This the first prospective study showing that a measure of microstructural deterioration identifies women before an imminent fracture, and does so better than BMD and FRAX. Measurement of microstructure is likely to improve identification of women in need of immediate treatment. Disclosure of Interest: R. Zebaze Grant/research support from: from Amgen, Merck Sharp & Dohme, Servier, Warner-Chilcott, AKP, Genzyme, Sanofi, GSK, Board membership: Straxcorp, Company employee of: Straxcorp, Stock ownership or royalties: Straxcorp, E. Seeman Grant/research support from: Amgen, Allergan, Asahi, Genzyme, andWarner Chilcott, Consultant/speaker’s bureau/advisory activities: Amgen, Allergan, Asahi, Genzyme, and Warner Chilcott, Board membership: Straxcorp, Company employee of: Straxcorp, Stock ownership or royalties: Straxcorp