Hypomethylation of the RUNX2 Gene Is a New Potential Biomarker of Primary Osteoporosis in Men and Women.

The search for the molecular markers of osteoporosis (OP), based on the analysis of differential deoxyribonucleic acid (DNA) methylation in bone cells and peripheral blood cells, is promising for developments in the field of the early diagnosis and targeted therapy of the disease. The Runt-related transcription factor 2 (RUNX2) gene is one of the key genes of bone metabolism, which is of interest in the search for epigenetic signatures and aberrations associated with the risk of developing OP. Based on pyrosequencing, the analysis of the RUNX2 methylation profile from a pool of peripheral blood cells in men and women over 50 years of age of Russian ethnicity from the Volga-Ural region of Russia was carried out. The level of DNA methylation in three CpG sites of the RUNX2 gene was assessed and statistically significant hypomethylation was revealed in all three studied CpG sites in men (U = 746.5, p = 0.004; U = 784, p = 0.01; U = 788.5, p = 0.01, respectively) and in one CpG site in women (U = 537, p = 0.03) with primary OP compared with control. In the general sample, associations were preserved for the first CpG site (U = 2561, p = 0.0001766). The results were obtained for the first time and indicate the existence of potentially new epigenetic signatures of RUNX2 in individuals with OP.

Peak Bone Mass Formation: Modern View of the Problem.

Peak bone mass is the amount of bone tissue that is formed when a stable skeletal state is achieved at a young age. To date, there are no established peak bone mass standards nor clear data on the age at which peak bone mass occurs. At the same time, the level of peak bone mass at a young age is an important predictor of the onset of primary osteoporosis. The purpose of this review is to analyze the results of studies of levels of peak bone mass in general, the age of its onset, as well as factors influencing its formation. Factors such as hormonal levels, body composition, physical activity, nutrition, heredity, smoking, lifestyle, prenatal predictors, intestinal microbiota, and vitamin and micronutrient status were considered, and a comprehensive scheme of the influence of these factors on the level of peak bone mass was created. Determining the standards and timing of the formation of peak bone mass, and the factors affecting it, will help in the development of measures to prevent its shortage and the consequent prevention of osteoporosis and concomitant diseases.

Clinical and Genetic Characteristics of Calvarial Doughnut Lesions with Bone Fragility in Three Families with a Reccurent SGMS2 Gene Variant.

Calvarial doughnut lesions (CDL) with bone fragility with or without spondylometaphyseal dysplasia (MIM: #126550) is a rare autosomal dominant skeletal disorder characterized by low bone mineral density, spinal and peripheral fractures, and specific sclerotic lesions of the cranial bones. In the current classification of skeletal disorders, the disease is included in the group of bone fragility disorders along with osteogenesis imperfecta. The disease is caused by pathogenic variants in the SGMS2 gene, the protein product of which is sphingomyelin synthase 2, which primarily contributes to sphingomyelin (SM) synthesis-the main lipid component of the plasma membrane essential for bone mineralization. To date, 15 patients from eight families with CDL with bone fragility have been described in the literature, and a recurrent variant c.148C>T (p.Arg50Ter) in the SGMS2 gene has been identified, which was found in patients from six families. We diagnosed the disease in 11 more patients from three unrelated families, caused by the same heterozygous nonsense variant c.148C>T (p.Arg50Ter) in the SGMS2 gene. Our results show wide interfamilial and intrafamilial phenotypic variability in patients with a detected recurrent variant in the SGMS2 gene, the presence of which must be taken into consideration in the diagnosis of the disease. The primary analysis of this variant will contribute to optimal molecular genetic diagnostics, which can reduce diagnostic costs and time.