Abstract: BACKGROUND: Severe segmental infectious bone defects of the tibia pose a significant challenge in orthopedic treatment due to persistent infection, poor local blood supply, and poor soft tissue conditions. Although bone transplantation techniques are the main repair method, the healing process is complex and influenced by multiple factors. The underlying mechanisms are not yet fully understood. Therefore, it is necessary to conduct in-depth research on the healing characteristics and influencing factors to optimize the treatment.
OBJECTIVE: To explore the healing characteristics and influencing factors of large-segment infectious bone defect of tibia repaired by bone transfer and analyze the influencing factors. 
METHODS: A total of 98 patients with large-segment infectious bone defect of the tibia treated by Ilizarov bone transfer in The First Affiliated Hospital of Xinjiang Medical University from May 2020 to October 2022 were selected as the study subjects. According to the clinical criteria of delayed or nonunion and union of fractures, they were divided into delayed or nonunion group (n=48) and union group (n=50), and the general data of the two groups were compared. A combined model was constructed. Cox regression analysis was used to evaluate the relationship between the fluctuation of bone specific alkaline phosphatase, N-terminal fragment of osteocalcin and amino terminal propeptide of type 1 procollagen and healing. Least Absolute Shrinkage and Selection Operator regression and multiple Logistic regression were used to analyze the risk factors affecting healing. After adjusting for confounding variables in Cox proportional risk model, the association of bone specific alkaline phosphatase, bone specific alkaline phosphatase, and amino terminal propeptide levels with poor healing was analyzed. The prediction model of regression equation y=1-1/(1+e-z) was established and verified.  
RESULTS AND CONCLUSION: (1) There were significant differences in long-term smoking history, diabetes mellitus, soft tissue injury, fibula fracture, wound infection, weight bearing started within 6 weeks after surgery, displacement direction, bone displacement distance, bone specific alkaline phosphatase, N-terminal fragment, and amino terminal propeptide levels between delayed union or nonunion group and union group (P < 0.05). (2) The combined model showed that regardless of whether bone specific alkaline phosphatase, N-terminal fragment, and amino terminal propeptide were within the normal range; the risk of poor healing increased by 3%, 2%, and 4%. (3) Least Absolute Shrinkage and Selection Operator regression and multifactor Logistics regression analysis showed that after adjusting for potential confounders, soft tissue injury, weight bearing started within 6 weeks after surgery, wound infection, combined fibula fracture, and decreased levels of bone specific alkaline phosphatase, N-terminal fragment, and amino terminal propeptide were all independent risk factors for healing (P < 0.05). (4) After the adjusted Cox proportional risk model, bone specific alkaline phosphatase (HR=0.67, 95%CI:0.54-0.87, P < 0.001), N-terminal fragment (HR=0.80, 95%CI:0.55-0.99, P < 0.001), amino terminal propeptide (HR=0.85, 95%CI:0.43-0.97, P < 0.001) were important influencing factors for poor healing in patients with large-segment infectious bone defects of the tibia. (5) With the decrease of bone specific alkaline phosphatase, N-terminal fragment, and amino terminal propeptide levels (Q2-Q4), the correlation effect also increased, and the differences in trend test were statistically significant (Pfor trend < 0.05). Through Bootstrap self-sampling, the prediction model had good differentiation and accuracy. (6) It is concluded that the reduction of serum bone transformation markers bone specific alkaline phosphatase, N-terminal fragment, and amino terminal propeptide levels after the repair of large-segment infectious bone defects of the tibia by Ilizarov bone transfer is closely related to poor healing, and soft tissue injury, weight bearing started within 6 weeks after surgery, wound infection, combined fibula fracture and bone specific alkaline phosphatase, N-terminal fragment, and amino terminal propeptide levels are important factors affecting healing of patients. 

Key words: ">tibial bone defect, Ilizarov technology, healing characteristics, delayed healing, soft tissue injury, wound infection, influencing factors