MiRNAs, known as the family of short non-coding RNAs, are key repressors of gene expression and play an important role in the regulation of osteogenesis, interact with signaling molecules of bone remodeling, and control the processes of differentiation of bone cells. A study of the polymorphic variant rs2910164 (n. 303C>G) of the microRNA gene (miR-146a) and an assessment of its role in the formation of the risk of osteoporetic fractures and low bone mineral density (BMD) in a sample of postmenopausal women and men over 45 years of age was conducted. The C allele was found to be associated with a low level of bone mineral density in the lumbar spine in women. There were no significant associations of the studied locus with osteoporotic fractures in General and their separate localities in men and women, with a low level of BMD in General and various localities in men.

In recent genome-wide association studies (GWAS), several polymorphic loci of the osteoprotegerin (OPG) gene were significantly associated with bone mineral density (BMD) and fractures in men over 50 years of age and postmenopausal women. The objective of our study was to search for associations of rs3102735, rs3134069, rs2073617, rs2073618, rs3102734 and rs7844539 of the OPG gene with the risk of osteoporotic fractures and the level of BMD in individual and comorbid conditions in men and women from the Volga-Ural region of Russia. Material and Methods — 828 women and 496 men of various ethnic groups (Russians, Turks) were examined using two-energy x-ray absorptiometry (DEXA) in the femoral neck and lumbar spine. 1324 deoxyribonucleic acid (DNA) samples were genotyped using a fluorescent endpoint genotyping system, after that we searched for associations of these polymorphic loci with fractures and low BMD levels of various localizations. As a result, there was a significant association of rs3134069 and rs3102734 with fractures in general and in the peripheral parts of the skeleton, as well as rs7844539 and rs3102734 in women and rs2073618 in men with low BMD. Another significant association of rs3102734 and rs2073618 with low bone mineral density in the femoral neck was found in both genders. Conclusion — Polymorphic variants rs3134069, rs3102734, rs7844539 and rs3102734 are potential markers of the risk of osteoporetic fractures and the formation of low BMD in men and women from the Volga-Ural region of Russia.

Osteoporosis (OP) is a multifactorial bone disease belonging to the metabolic osteopathies group. Using the polygenic score (PGS) approach, we combined the effects of bone mineral density (BMD) DNA loci, affecting osteoporosis pathogenesis, based on GEFOS/GENOMOS consortium GWAS meta-analysis. We developed models to predict the risk of low fractures in women from the Volga-Ural region of Russia with efficacy of 74% (AUC = 0.740; OR (95% CI) = 2.9 (2.353–3.536)), as well as the formation of low BMD with efficacy of 79% (AUC = 0.790; OR (95% CI) = 3.94 (2.993–5.337)). In addition, we propose a model that predicts fracture risk and low BMD in a comorbid condition with 85% accuracy (AUC = 0.850; OR (95% CI) = 6.6 (4.411–10.608)) in postmenopausal women.

Osteoporosis is one of multifactorial diseases, it develops from interactions between the genetic component and the environment. However, the universal epigenetic markers of osteoporosis are not yet defined. Finding the risk factors will predict the risk of osteoporosis at the preclinical stage, help define the course and severity of the disease, and develop preventive measures based on them to reduce the risk of fractures. Expanding knowledge in the field of bone biology, especially in the genetics of osteoporosis and osteoimmunology, showed that osteoporosis is a disease that occurs not only due to hormonal or mechanical disorders, but also as a clinically and genetically heterogeneous disease, and there are still unknown pathogenetic links in its structure. Decreases in bone mass and matrix mineralization as well as changes in bone microarchitecture can have different pathogenetic patterns of development and, moreover, there are unknown links of the pathogenesis of osteoporosis. It is possible that DNA methylation is one of these links and a mechanism for epigenetic regulation of gene expression. Evidence exists that this mechanism alongside regulatory miRNAs and post-translational modifications makes a significant contribution to the central processes of bone remodeling; however, the results of various studies vary greatly, and, therefore, there is a need to understand the significance of the accumulated data and to make them consistent. The purpose of this review is to compile and systematize data on the role of DNA methylation in bone metabolism in normal and pathological conditions, in the formation of osteoporosis, and to assess achievements and trends in this field of research and technologies for studying DNA methylation.

The identification of genetic loci and biochemical markers associated with the risk of fractures and the level of bone mineral density (BMD) did not give an unambiguous answer about the molecular pathogenesis of osteoporosis (OP). There are still unresolved questions about the possibility of early diagnosis and prognosis of the course of the disease. The molecular effects of genetic variants located in the coding regions of the human genome are easy to study. However, most of the single nucleotide polymorphic loci that are associated with osteoporosis susceptibility are located in non-coding or intergenic regions. Their role in the pathogenesis of this disease is not fully understood. The use of biochemical markers in the diagnosis and monitoring of osteoporosis therapy does not allow developing approaches to early diagnosis of the disease before a fracture occurs. Significant problems arise in the interpretation of research results for use in clinical medicine. But the combination of multidisciplinary data, such as genome-wide association study (GWAS), changes in the patterns of biogenic elements of bone remodeling, catalytic activity of a number of enzymes, and protein expression has significantly expanded the understanding of the key links in the pathogenesis of the disease. The article reviews and summarizes the latest advances in multiomics studies of osteoporosis, including bionformatic analysis to find key risk factors for the development of OP, as well as pharmacogenetic aspects of modern therapy of the disease.