The Epigenome at the Crossroad Between Social Factors, Inflammation, and Osteoporosis Risk

Both genetic and environmental factors are involved in the pathogenesis of osteoporosis and other skeletal disorders. Epidemiological studies have revealed an influence of a variety of social factors, including socioeconomic status (SES) on the risk of osteoporosis. The mechanisms involved are complex and still incompletely elucidated. Nevertheless, a variety of clinical risk factors known to influence skeletal homeostasis have been reported as being socially patterned, including nutrition, exercise, and other lifestyles, among others. These factors may impact the skeleton through a variety of mechanisms. Among them, there is increasing evidence for a role of DNA methylation and other epigenetic mechanisms. Indeed, several studies of human cohorts and experimental models showed that social deprivation is associated with changes in the methylation pattern of a number of genes, including some involved in stress and inflammatory responses. The influence of socioeconomic factors may be important not only during postnatal life but also in utero and may be transmitted to future generations by its direct effect on peripheral and target tissues and perhaps through epigenetic inheritance. Although the exact relevance of these pathways in humans has not been fully elucidated yet, they bring attention to the influences of social factors on the skeletal health of the individuals and their descendants. Therefore, they also bring forward our responsibility for both present and future generations.