CURRENT INSIGHTS INTO THE GENETIC DETERMINANTS OF TRAUMATIC COMPLICATIONS AND BONE-TISSUE REGENERATION
DOI:
https://doi.org/10.35220/2523-420X/2025.3.23Keywords:
RANKL; VEGF; TNF-α; IL-6; bone tissue; regeneration; dentistry; traumatic complications; molecular geneticsAbstract
Traumatic injuries of bone tissue in adults result from a multifactorial interaction of mechanical, inflammatory, and genetically determined factors. Imbalance within the RANKL / RANK / OPG axis, hyper-expression of the pro- inflammatory cytokines TNF-α and IL-6, and insufficient VEGF-mediated angiogenesis provoke pathological resorption, delayed remodelling, and the development of post-traumatic complications. Although anti-resorptive antibodies, selective oestrogen-receptor modulators, and tissue-engineering approaches are available, unified personalised protocols for prevention and treatment remain under-developed. The purpose of the study was to systematise contemporary clinical and experimental evidence concerning the role of genetic determinants (TNFSF11, TNFRSF11A/B, VEGFA, TNF, IL6) in the emergence of traumatic complications and in bone-tissue regeneration, with the aim of identifying effective and safe molecular therapeutic targets. Materials and methods. A targeted narrative review (2005–2025) was conducted in accordance with PRISMA-ScR. Searches were performed in PubMed, Scopus, Web of Science, Embase, and Google Scholar. Sixty-five sources met the inclusion criteria (fracture models, genetic association studies, clinical trials of anti-resorptive and pro-angiogenic agents; adult population ≥ 18 years). Study design, molecular interventions, and morphometric and clinical end-points (bone mineral density, incidence of delayed union, rate of defect closure) were assessed. Research results. In a rat model of osteoporotic fractures, raloxifene increased bone mineral density and OPG expression 1.4-fold while reducing RANKL and RANK levels 1.3-fold (P < 0.05), achieving complete radiological union after 4 weeks. In rabbits with mandibular bone defects, implantation of a PEK-BBC/VEGF composite promoted mature trabecular formation and elevated VEGF expression 2.8-fold versus controls (P < 0.01), with 75 % defect closure by week16. The TNFSF11*G/G and TNF-308A genotypes were associated with a two-fold higher risk of delayed union, whereas carriers of VEGFA-936C exhibited accelerated osteogenesis. TNF-α blockers (infliximab, adalimumab) reduced the rate of periprosthetic osteolysis by 28 % and the frequency of revision surgery in patients with rheumatoid arthritis (P < 0.05). Conclusions. Genetic stratification of patients according to TNFSF11, TNFRSF11A/B, VEGFA, TNF, and IL6 polymorphisms, combined with targeted anti-resorptive, anti-inflammatory, and pro-angiogenic therapy, minimises the risk of post-traumatic complications and optimises reparative osteogenesis.Further prospective randomised studies are required to standardise personalised protocols and to evaluate the long-term safety of multi-component approaches.
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