GENETIC RISK FACTORS FOR OSTEOPOROSIS AND THEIR SIGNIFICANCE IN MODERN TRAUMATOLOGY AND ORTHOPEDICS

Abstract

Osteoporosis is characterized by reduced bone strength and fractures resulting from minimal trauma; however, identified genetic associations have not provided a sufficiently precise basis for individual prognosis. In the fields of traumatology and orthopedics, the application of such data is complicated by the need to distinguish between identifying the hereditary cause of bone fragility, assessing fracture risk, and selecting an appropriate treatment strategy. This study aimed to critically evaluate genetic risk factors for osteoporosis and determine their potential utility in diagnosing bone fragility, predicting fractures, and managing patients. The analysis drew upon 43 sources, including original research, reviews, clinical guidelines, and professional organization statements published between 2022 and 2026. Literature searches were conducted via PubMed, as well as through the websites of scientific journals and relevant professional institutions. The study employed comparative analysis, systematization, and critical qualitative assessment of the data, accounting for sample composition, the specific genetic markers investigated, clinical outcomes, and the independent replication of findings. The diagnostic efficacy of identifying pathogenic variants was evaluated separately from the accuracy of polygenic risk prediction and the evidence supporting genotype-guided treatment. The review examined rare pathogenic variants, polygenic predisposition, epigenetic modifications, and genetic factors influencing bone recovery. This comparison helped differentiate between approaches that clarify the underlying cause of the disease and those whose clinical utility remains insufficiently substantiated. Key challenges identified include sample heterogeneity and the limited incremental accuracy provided by genetic data: causative variants were detected in 20.8% of 394 selected patients, while in another study, the inclusion of polygenic scores increased the area under the diagnostic curve from 0.72 to 0.74. To justify the use of genetic data, it has been proposed to evaluate diagnostic and prognostic approaches separately by comparing them against standard clinical assessment in independent patient cohorts, while also assessing changes in treatment strategy, the incidence of fractures, and surgical outcomes.