The epigenetic regulation of bone mass

Osteoporosis is a major cause of morbidity and mortality through its association with age-related fractures. Evidence is growing that peak bone mass is an important contributor to bone strength during later life and is influenced by many factors, some of which may be modifiable during childhood. In addition, evidence has accrued that fracture risk might be programmed during intrauterine life, although the mechanisms initiating these responses remain unclear. Emerging evidence has strongly suggested that epigenetic mechanisms, such as DNA methylation and histone modification, may underlie the process of developmental plasticity. Numerous studies in animal models have shown that during embryonic and fetal development, maternal or environmental factors can disrupt patterns of DNA methylation. For example, the embryos of pregnant rats fed a low-protein diet during the pre-implantation period of pregnancy showed altered development in multiple organ systems. This dysregulation of developmental programming via abnormal DNA methylation may permit specific genes to undergo inappropriate expression during adult life, resulting in disease development. This review will summarize the relationship between developmental plasticity and osteoporosis and will focus upon the possible mechanisms by which the epigenetic regulation of bone mass may occur using two models: Maternal vitamin D status and placental calcium transfer, and the hypothalamic-pituitary-adrenal axis.