Basic And Clinical Research Of Pain-related Intervention In OVCF

Part Ⅰ:A pain that is easily overlooked:referred pain caused by OVCF[Purpose]Some patients with OVCF complain of pain in the lumbosacral region,buttocks,ilium,and even legs,but there is no obvious nerve compression on imaging At the same time,these pain areas were not consistent with the dermatome-innervated areas of the injured vertebral body found on imaging.Therefore,only 1/3 of OVCF patients can get a clinical diagnosis in time.The aim of this study was to analyze the clinical characteristics and treatment effects of patients with OVCF complicated with referred pain.To deepen the understanding of the pain involved in OVCF,so as to improve the early diagnosis rate of OVCF,alleviate the pain of patients,and improve the quality of life of patients.[Method]We retrospectively analyzed 173 patients with OVCF who were treated at our Spine Center between June 2013 and October 2019,of which 56(32.37%)were complicated by somatic referred pain.Patients with OVCF who meet the inclusion criteria are classified according to the patient’s self-described area of referred pain and are eventually treated with PKP.VAS and ODI scores were used to evaluate treatment effects at different time points.[Results]There were 11 males(19.6%)and 45 females(80.4%).Age 55 to 91 years(average 73.2±7.2 years),symptom duration 3 to 60 days(average 23.1±14.2 days).Among them,38(67.9%)patients had a clear history of injury,and the time interval from injury to the appearance of referred pain was 12 to 26 days(average 18.1±3.8 days),and the corresponding bone density value T value was-3.3±0.4.The coefficient of BMD in the linear regression equation was-4.51(P<0.001).According to the classification of OVCF-referred pain,there were 27 cases of type A(48.2%),12 cases of type B(21.2%),8 cases of type C(14.3%),3 cases of type D(5.4%),and 6 cases of type E(10.7%).For fixed time nodes,there was no statistically significant difference in VAS and ODI scores between different types of patients before and after surgery for 6 months(P>0.05).In the same type,there were significant differences in VAS and ODI scores between preoperative and postoperative time points(P<0.05).[Conclusion]In clinical work,the referred pain of OVCF should be paid attention to.We summarize and classify the characteristics of referred pain caused by OVCF,which will help to improve the early diagnosis rate of OVCF patients,and provide reference for the prognosis after PKP treatment.There is a significant correlation between referred pain and osteoporosis,which also suggests that the pain threshold regulation of DRG in osteoporosis may be related to the occurrence of referred pain.Part Ⅱ:Novel anti-osteoporosis drug SW033291 improves pain action and mechanism exploration in OVX mice[Purpose]Osteoporosis is a metabolic disorder of the systemic bone that increases the risk of fragile fractures.It also lowers the patient’s pain threshold and causes diffuse pain.Once OVCF is confirmed,anti-osteoporosis therapy is present throughout the process.SW033291 is a novel anti-osteoporosis drug.However,no scholars have studied the changes in pain.The objective of this study was to verify and evaluate the analgesic effect of SW033291 and to explore the molecular mechanism mechanisms of its pain threshold regulation.[Method]OVX mouse model was constructed and mice are subjected to pain-related behavioral tests once a month during the experiment.After 12 weeks of molding,the use of SW033291 small molecule drugs was used for intervention after the molding was confirmed.4 weeks after medication.Micro CT scan,serum ELISA testing,DRG transcriptome sequencing were performed.[Results]The pain behavior evaluation showed that after OVX molding,the PWMT of mice gradually decreased to 12 weeks after surgery,and after OVX molding,SW033291 drug intervention was given,and the PWMT of mice was significantly relieved compared with the OVX+NS group.In hot plate experiments,mouse heat withdrawal claws last longer after the SW033291 intervention.Micro CT showed a significant reduction in cancellous bone in the OVX-NS group compared to the Sham group.The OVX-SW group had more bone mass than the OVX-NS group.Serum ELISA showed an increase in P1NP and a decrease in CTX in the OVX-SW group compared with OVX-NS.A total of 26655 genes were obtained by DRG transcriptome sequencing,of which 24436 genes were expressed in the OVX+SW group and the OVX+NS group,1302 genes were expressed in the OVX+SW group alone,and 917 genes were expressed in the OVX+NS group alone.Through bioinformatics analysis,the genes related to pain threshold regulation include Chil3,Fzd7,Lcn2,Fgr,Camp,Ccrl,Col3al,Retnlg,S100a9,Mmp9,Mmp8,S100a8[Conclusion]The small molecule drug SW033291 can not only improve osteoporosis,but also improve pain.Chil3,Lcn2,Fgr,Camp,Ccrl,Col3a1,Retnlg,S100a9,Mmp9,Mmp8,S100a8 have potential drug targets for pain threshold regulation.Especially Lcn2,Fgr,Camp should be focused onPart Ⅲ:Analysis of percutaneous kyphoplasty or short-segmental fixationcombined with vertebroplasty in the treatment of Kummell disease[Purpose]Kummell disease is a special type of OVCF with poor surgical efficacy and a high complication rate.In recent years,short-segment internal fixation combined with vertebroplasty(SSF+VP)has provided a new option for the treatment of Kummell disease.The objective of this study was to assess the efficacy of PKP and SSF+VP and to provide evidence-based medical support for the decision-making process for the treatment of Kummell disease without neurological deficits.[Method]Databases including MEDLINE(PubMed)and EMBASE(Ovid)were searched(1 January 1947-6 April 2019)for randomized controlled or cohort studies of PKP and SSF+VP for Kummell disease.Two researchers independently assessed the eligibility of studies retrieved from the database based on predetermined selection criteria.Postoperative evaluation indicators included operation time,bleeding volume,VAS score,ODI score,local Cobb angle of the vertebral body,and bone cement leakage.When the data differ significantly,a random effects model is used for analysis.Conversely,when the results show no statistical heterogeneity,a fixed-effects model is used to estimate the overall effect size.[Results]Three retrospective case-control studies were covered at the end.The differences in bleeding volume and duration of surgery were statistically significant,with the combined weighted mean differences(WMDs)(95%CI)of 0.204.46(210.97,197.93)and 98.98(141.63,56.32),respectively.The comprehensive data showed that the differences in VAS score,ODI score,local vertebral Cobb angle,and cement leakage were not statistically significant.[Conclusion]PKP and SSF+VP each have their own advantages and disadvantages in KD treatment.PKP can shorten the operation time and reduce the amount of blood loss.Theoretically,SSF+VP can enhance internal fixation stability,but this advantage still needs to be observed.Part Ⅳ:Rationality study of development of intravertebral expansion device based on three-column fixation[Purpose]Reducing bone cement loosening,maintaining the vertebral body height after intraoperative reduction,reducing the risk of bone cement leakage,and reducing the elastic modulus of implants are still urgent issues to be solved in current spine surgery.In order to further optimize the surgical treatment of OVCF,The purpose of this study was to design an intravertebral expansion device based on three-column fixation and to preliminarily verify its rationality..[Method](1)Design and optimization of expansion performance of three-column fixed vertebral internal expansion device.Use Unigraphics,Autodesk CAD,Abaqus software design devices(stent+hollow pedicle nail part)and supporting tools.According to the drawings of the prototype device and supporting tools,the device is physically verified.Analyze physical verification results.The design structure is re-optimized according to the results and the plates are replaced.Then carry out finite element simulation test and physical verification.(2)Verification of the mechanical characteristics of the stent of the three-column fixed intravertebral expansion deviceUsing Unigraphics,Autodesk CAD,Abaqus software,universal experimental machine,computer simulation and physical verification methods,the axial pressure,short shrinkage analysis,short shrinkage and pressure bearing characteristics of the bracket are verified.Grasp the relevant performance parameters of the stent,and determine the best working area and performance of the stent.(3)Simulated implantation of expansion devices in the three-column fixed vertebral bodyBTB of different densities was used to simulate the implantation of normal cancellous bone and osteoporosis in clinical surgery,and the torque value that the surgeon needed to apply to the supporting tool during the implantation process was assessed by using the self-designed adapter combined with the torque wrench to assess the torque value to be applied to the supporting tool,and the diffusion of the bone cement in the BTB after the expansion of the stent and the bone cement perfusion was assessed by CT.(4)Finite element analysis of the three-column fixed intravertebralexpansion device in the vertebral bodyObtain lumbar spine data of an elderly woman and build L1 vertebral body models with the help of Mimics,Ansys,Geomagic,and SolidWorks software.Stents and hollow pedicle screws are assembled in the L1 cone body model.There are two cases:one is a bracket only,and the other is a bracket+screw.The assembled model is imported into Ansys software to build two models,normal vertebral body and osteoporosis vertebral body.Fixing the bottom of the L1 cone,applying 500 N force to the top of the L1 cone to simulate self-weight and 10000N.mm simulating the stress conditions of five physiological positions of neutrality,forward flexion,posterior extension,lateral flexion,and rotation,respectively.[Results](1)Design and optimization of expansion performance of three-column fixed vertebral internal expansion deviceThe three-column fixed intravertebral expansion device mainly includes a skeletonized stents made of TA3G,a hollow pedicle screw made of TC4 and a stainless steel supporting instrument with expansion function.The device is optimized with materials and structures to achieve the desired expansion of the skeletonized stent and to achieve three-column fixation through hollow pedicle screws.(2)Verification of the mechanical characteristics of the stent of the three-column fixed intravertebralexpansion deviceWe design the stent with an optimal working range of 2.5 to 3.5mm.The achievable opening height is:10.39～11.09mm,and a single stent can provide a load of 87～105N,which can provide sufficient support to maintain the height of the intraoperative vertebral body.(3)Simulated implantation ofexpansion devices in the three-column fixed vertebral bodyThe three-column fixed intravertebral expansion device was successfully implanted in different BTB modules with the assistance of supporting tools,and the normal cancellous bone BTB expansion torque was 1.07±0.21(N.m),and the osteoporotic bone BTB expansion torque was 0.91±0.15(N.m)and there was a significant difference(P<0.05).CT effects show that the stent expands as expected under both osteoporosis and normal cancellous bone conditions,with satisfactory bone cement diffusion.(4)Finite element analysis of the three-column fixed intravertebral expansion device in the vertebral bodyIn the finite element simulation model of vertebral fracture healing,the displacement of the stent in the neutral position(0.086 mm),anteroposterior(0.1345 mm),posterior extension(0.0978 mm),lateral flexion(0.1250 mm),rotation(0.0875 mm)in the neutral position(0.0145 mm),anteflection(0.0269 mm),posterior extension(0.0252 mm),lateral flexion(0.0267 mm)in normal vertebral body was significantly greater than that of the stent in the normal vertebral body in the neutral position(0.0145 mm),anteflection(0.0269 mm),posterior extension(0.0252 mm),lateral flexion(0.0267 mm),Displacement at rotation(0.0244mm)in the position.However,the displacement of the device after the stent+screw fixation scheme was adopted in the osteoporosis vertebral body,and the displacement of the device was significantly reduced in the neutral position(0.0239 mm),anteflection(0.0326 mm),posterior extension(0.0151 mm),lateral flexion(0.0322 mm),and rotation(0.0354 mm).Similarly,in the comparison of normal vertebral implant stents and normal vertebral implant stents+screw schemes,there was no significant difference in device displacement under the above 5 positions.Only slightly down.[Conclusion]The three-column fixation-based intravertebral expansion device is capable of effective expansion,and preliminary results show that the mechanical properties after expansion meet all moderate and some severe OVCF vertebral high reduction maintenance needs.With the help of supporting tools,it can be implanted,expanded,and infused with bone cement.The three-column fixation method of stent+hollow pedicle screw in the face of osteoporosis can significantly improve the stability of the device and may also have the potential to reduce vertebral re-fracture.