Abstract Background Early life vitamin D exposure is linked to later skeletal health with maternal vitamin D status in pregnancy associated with neonatal bone mass. The MAVIDOS study has demonstrated that vitamin D supplementation leads to reduced RXRA DNA methylation. Mice exposed to early life vitamin D deficiency have reduced bone mass and bone accrual in response to mechanical loading. Using the tibiae of these mice, we have examined the effect of diet and mechanical loading on the DNA methylation of promoters of genetic loci important for bone growth and development and their association with bone strength. Results Mechanical loading of mouse tibiae leads to a reduction of RXRA DNA methylation. Early life vitamin D deficiency is associated with altered methylation of osterix and Runx2 in these bones. Tibia strength was also demonstrated to be associated with a change in DNA methylation status in CpGs of the vitamin D receptor (VDR), ostrix, and RXRA genes. Conclusions We have shown for the first time that mechanical loading of bone and early life vitamin D deficiency leads to changes in the epigenome of this tissue in key genes in the vitamin D and osteoblast differentiation pathway.
Abstract Bone health in children with osteogenesis imperfecta is monitored using radiographs and dual-energy X-ray absorptiometry, which have limitations. High-resolution peripheral quantitative CT can non-invasively derive bone microarchitectural data. Children with severe osteogenesis imperfecta have fragile deformed bones, and positioning for this scan can be difficult. We assessed the feasibility of high-resolution peripheral quantitative CT in nine children aged 9–15 years with osteogenesis imperfecta and compared results with dual-energy X-ray absorptiometry and with healthy controls. All nine recruited children were successfully scanned and showed no preference for either modality. It therefore appears feasible to perform high-resolution peripheral quantitative CT in children with osteogenesis imperfecta aged 9 years and older. Future studies should focus on understanding the clinical implications of the technology in this patient cohort.
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