Epigenetic regulation of bone mass

Abstract

Osteoporosis, characterised by low bone mass, poor bone structure, and an increased risk of fracture, is a major public health problem. There is increasing evidence that the influence of the environment on gene expression, through epigenetic processes, contributes to variation in BMD and fracture risk across the lifecourse. Such epigenetic processes include DNA methylation, histone and chromatin modifications and non-coding RNAs. Examples of associations with phenotype include DNA methylation in utero linked to maternal vitamin D status, and to methylation of target genes such as OPG and RANKL being associated with osteoporosis in later life. Epigenome-wide association studies and multi-omics technologies have further revealed susceptibility loci, and histone acetyltransferases, deacetylases and methylases are being considered as therapeutic targets. This review encompasses recent advances in our understanding of epigenetic mechanisms in the regulation of bone mass and osteoporosis development, and outlines possible diagnostic and prognostic biomarker applications.

Keywords: DNA methylation; bone; development; epidemiology; epigenetics; osteoporosis.

Figure 1

(Left Panel) In the Southampton Women’s Survey, perinatal umbilical cord RXRA methylation was inversely associated with maternal late pregnancy estimated free 25(OH)-vitamin D index and with offspring bone mass in childhood[93]. (Right Panel) Subsequently, in the MAVIDOS trial, maternal pregnancy supplementation with cholecalciferol 1000 IU/day versus placebo led to a reduction in umbilical cord RXRA methylation at birth[94]. Adapted with permission from Harvey et al, 2014[93] and Curtis et al., 2018[94].