Identification of genetic polymorphisms associated with complicated postoperative course and unsatisfactory outcomes of reconstructive interventions on the facial skull bones using bone autografts

Introduction Enhancing the effectiveness of reconstructive and restorative operations in patients with the facial skull bone defects and the prevention of complications in the postoperative period is a pressing issue in modern maxillofacial surgery. One of the promising directions in addressing this problem is the application of a personalized approach to choosing the treatment strategy in patients, including that one based on the study of genetic predisposition to metabolic disorders and reparative regeneration of bone tissue. A number of genes associated with the main mechanisms regulating remodelling and reparative regeneration of bone have polymorphisms, which have been proven to increase the risk and unfavorable progression of osteoporosis. However, their potential impact on bone regeneration and remodelling of bone grafts in the replacement of jaw defects and pre-implantation preparation has not been studied.

OBJECTIVE - to identify genetic polymorphisms that most significantly affect the processes of bone tissue regeneration and remodelling of free bone autografts, as well as those associated with an increased risk of complications in patients following the replacement of jaw defects and pre-implantation preparation (augmentation of the alveolar processes).

Materials and methods The study included 40 patients who underwent replacement of jaw defects and augmentation of alveolar processes using free bone autografts obtained from local and distant donor zones. In all patients, 16 genes and their polymorphisms that affect bone tissue metabolism and increase the risk of osteoporosis were analyzed using PCR. The effectiveness of surgical interventions, the frequency and nature of postoperative complications were studied in the immediate and late postoperative period using clinical methods and CBCT. The effect of genetic polymorphisms on the risk of complications and unfavorable outcomes of surgical interventions was studied by univariate and multivariate logistic regression models, calculating odds ratios with 95% CI. A significance level of p<0.05 was considered statistically significant.

Results Among 40 patients, 14 experienced various complications related to the development of inflammatory processes, disruptions in reparative regeneration, and remodelling of the graft in the recipient area. An increase (p<0.05) in the risk of complications was found for patients with polymorphisms of the RANKL CT genes [rs9594738] and RANKL CT [rs9594759], with odds ratios (OR) of 6.1 (95% CI 1.1-34.0) and 6.1 (95% CI 1.1-35.0) respectively, as well as an increased risk (p<0.02) for patients with the ESR1: -397 T>C gene, OR=13.5 (95% CI 1.5-124).

Conclusions Genetic polymorphisms associated with an increased risk of osteoporosis and metabolic disorders of bone tissue likely influence the course of the postoperative period in patients who underwent reconstructive surgeries and pre-implantation preparation on the upper and lower jaw. The greatest effect on the risk of complications, including the loss of bone grafts, was observed with polymorphisms RANKL CT [rs9594738], RANKL CT [rs9594759], ESR1: -397 T>C, associated with the RANK-RANKL-OPG signalling pathway. The widespread application of techniques for detecting these polymorphisms in clinical practice for diagnostic and prognostic purposes requires further study and validation of these candidate genes in larger cohorts of patients from different ethnic groups, as well as the use of methods for multifactorial assessment of various genetic and epigenetic factors.