Epidemiological Investigation Of Fractures In Chinese Residents,Validation Of Fracture Nonunion Factors And Strategies For Promoting Fracture Healing

Part One Traumatic Fractures in China from 2012 to 2014:A National Survey of 512,187 IndividualsObjective:The China National Fracture Study（CNFS）has been conducted to provide a comprehensive and up-to-date national dataset of traumatic fractures across China.This study aims to report the national incidences and distributions of traumatic fractures that occurred in 2012,2013and 2014 and to analyze the risk factors.Methods:A national representative sample of individuals were selected from 24 rural counties and 24 urban cities of 8 provinces using stratified random sampling and the probability proportional to size（PPS）methodology.Participants were interviewed to identify whether they sustained traumatic fractures of the trunk and/or four extremities that had occurred in 2012,2013,and 2014.The main risk factors associated with traumatic fractures were analyzed by multiple logistic regression models.Results:A total of 512,187 individuals,including 259,649 males and252,538 females,participated in the CNFS.The population-weighted incidence rates of traumatic fractures in China were calculated to be 2.5（95%CI 2.2-2.8）per 1,000 population in 2012,2.8（95%CI 2.5-3.3）in 2013 and3.2%（95%CI 2.8-3.6）in 2014.The population-weighted incidence rates of fragility fractures among participants aged 65 years and older were calculated to be 27.4（95%CI 21.4-33.4）per 1,000 population in 2012,36.0（95%CI28.6-43.5）in 2013 and 42.4（95%CI 34.9-49.9）in 2014.The most common cause of fracture was low-energy injuries,followed by traffic accidents.For all age groups,sleeping less than 7 hours was a risk factor for traumatic fractures.Alcohol consumption and previous fracture history were identified as risk factors for adults aged 15 years and over.Cigarette smoking was found to be a risk factor for males aged 15-64 years old.For individuals aged 15-64years old,underweight incurred a risk effect for males and overweight for females.Alcohol consumption,sleeping less than 7 hours per day,living in the central and eastern regions,a body mass index less than 18.5kg/m² and having a previous fracture history were identified as strong risk factors for fragility fractures.Conclusions:The first nationwide fracture epidemiological survey with national representative,rigorous sampling design,standardized methods,comprehensive investigation content,rich information,large sample size and wide coverage was completed.The fracture incidence,risk factors and fracture injury characteristics of different populations was reported.The largest authoritative database with sample size was established.Part Two Development and validation of a risk prediction model for postoperative nonunion of femoral shaft fracturesObjective:To explore the factors influencing postoperative non-union of femoral shaft fractures and development a predictive model.Methods:Patients with femoral shaft fractures treated in the Third Hospital of Hebei Medical University from January 1,2015 to December 31,2021 were retrospectively enrolled.Patients treated from January 2015 to December 2019 were selected as the development group and those from January 2020 to December 2021 as the external validation group.Bootstrap resampling was performed to obtain the internal validation group.Data were obtained by telephone follow-up and medical record inquiry.Multivariate logistic regression analysis was used to screen the influencing factors of postoperative non-union.A risk prediction model was constructed and the corresponding nomogram was drawn in the development group.The discrimination,calibration and clinical effectiveness of the model were evaluated through the internal and external validation.Results:A total of 729 patients with femoral shaft fractures met the inclusion and exclusion criteria,aged 25.1±17.2 years,including 554 males（76.0%）and 175 females（24.0%）.They were divided into two groups:the development group（n=617）and the external validation group（n=112）.According to multivariate logistic regression analysis,type B（OR=4.565,95%CI 1.951～10.684）and type C（OR=4.609,95%CI 1.657～12.819）,bone defect（OR=3.568,95%CI 1.623～7.843）,smoking（OR=3.366,95%CI1.773～6.387）,and postoperative infection（OR=2.964,95%CI 1.209～7.270）were independent risk factors for postoperative non-union of femoral shaft fractures.The C-indices were 0.818（95%CI,0.764～0.872）in the development group and 0.781（95%CI,0.652～0.910）in the external validation group,and the C-index of internal validation was 0.804.The Hosmer-Lemeshow test showed good fitting of the model（all P>0.05）,which was consistent with the results of the calibration plots.Decision Curve Analysis indicated that the clinical effectiveness was the best when the threshold probability was between 0.10 and 0.40.Conclusions:Patients with complex fracture,smoking,bone defect and postoperative infection are more likely to have postoperative non-union.The risk prediction of fracture patients through this model may be helpful to provide a clinical guidance to formulate targeted prevention and rehabilitation programs.Part Three Effect and mechanism study of novel multi-dimensional biomimetic three-dimensional printing Mg-MC/PLGA composite bone in promoting fracture healing and repairing material in individualized repair of long bone segmental defectsObjective:To prepare a new 3D printed multi-dimensional biomimetic magnesium mineralized collagen/polylactic acid-glycolic acid copolymer（Mg-MC/PLGA）composite bone repair material scaffold for the repair of segmental defects of long bones,so as to provide safe and effective regenerative implant material for the clinical repair of segmental defects of long bones.Methods:The MC bone meal containing 0,0.5%,10%and 20%Mg²⁺concentration were prepared by in-situ mineralization method.The PLGA was introduced into MC bone meal,and four kinds of Mg-MC/PLGA composite bone repair material scaffolds with Mg²⁺content were customized by low temperature deposition biological 3D printing technology.The pore structure,crystal composition and thermal stability of four kinds of magnesium ion concentration scaffolders were investigated by scanning electron microscope observation,X-ray diffraction,thermogravimetric analyzer,scanning electron microscope,energy spectrometer and high-performance automatic mercury injection instrument.The in vitro biocompatibility and cytotoxicity of the four scaffolders were evaluated by CCK-8,ghost pen cyclic peptide and DAPI staining and scratch tests,and the scaffolders with the best Mg²⁺content were determined.Finally,it was implanted into the defect of sheep femur.Imaging analysis was performed to evaluate the bone repair effect of Mg-MC/PLGA composite bone repair material with optimal Mg²⁺content on segmental defects of long bones.Results:Biological characterization showed that the MC materials doped with different concentrations of Mg²⁺were successfully prepared.Scanning electron microscopy showed that there were abundant interconnected pore structures on the surface and inside of the scaffold,with porosity≥70%.The vitro cell experiments showed that the four scaffolds had good cytocompatibility,among which 10%Mg-MC/PLGA material was superior to MC/PLGA,5%Mg-MC/PLGA and 20%Mg-MC/PLGA in Promote cell proliferation and cell migration.Animal experiments showed that the scaffold material in sheep gradually degraded and a large amount of new bone tissue grew into the defect site at 1,3 and 6 months after the operation.Conclusions:Mg-MC/PLA composite scaffolds with different Mg²⁺concentrations have pore structure and composition similar to cancellous bone,and have good biocompatibility and bone regeneration ability.The 10%Mg-MC/PLGA scaffolds have the best bone repair effect in the treatment of long bone segmental defects.