| BackgroundOsteonecrosis of the femoral head(ONFH)was a difficult disease in the field of Traditional Chinese Medicine Orthopedics and modern Orthopedic Surgery.There was no effective marketed drug specifically for the treatment of ONFH currently,therefore,the end-stage for patients with ONFH takes joint replacement as the therapeutic schedule.In the process of ONFH from the onset to the end-stage,various drugs and hip-preserving surgeries are applied,which is to keep the patient’s own hip joint and achieve the purpose of delaying or avoiding replacement.However,in all kinds of hip-preserving surgeries,even the most widely used and recognized core decompression and bone grafting cannot guarantee satisfactory efficacy.Traditional Chinese medicine(TCM),in mainland China,applied in the whole course management of ONFH,there are also many basic and clinical research reports on the treatment of ONFH with TCM alone.Professor Weiheng Chen of the research team has long been committed to the prevention and treatment of ONFH with TCM,and has achieved satisfactory efficacy in the treatment of early ONFH patients.Meanwhile,in long-term clinical observation,we noticed that even patients ONFH with collapsed femoral head,still have the value of using TCM to hip preservation,successful implementation "stay with collapse" under TCM hip-preservation treatment.Although it has been observed in long-term clinical practice that TCM is feasible in the treatment of "stay with collapse" ONFH,there were still some collapsed patients who cannot maintain a "stable" state for a long time after receiving treatment of TCM,and received further treatment such as joint replacement.Therefore,to explore whether TCM treatment of ONFH patients can successfully achieve the law behind the "stay with collapse",which can provide a basis for the accurate selection of middle-advanced ONFH patients "stay with collapse" cases under treatment of TCM.Objective1.Summarize the efficacy of TCM in the treatment of patients "stay with collapse" of middle-advanced ONFH,and provide a therapeutic basis for the treatment of middle-advanced ONFH patients with TCM.2.To analyze the related factors affecting the efficacy of TCM in the treatment of"stay with collapse" patients with middle-advanced ONFH,and provide a basis for improving the success rate of "stay with collapse" in ONFH.3.Through the simulation method of bone structure based on Three-dimensional image reconstructing,to reveal the influence of bone structure changes on the success of "stay with collapse" in patients with ONFH,and provided the basis for the level of image bone structure changes for the "stay with collapse".MethodsThis study included 290 ONFH patients with ARCO stage Ⅲ-Ⅳ who received comprehensive treatment of TCM including oral Chinese herbal medicine,small needle knife,and arterial infusion of Chinese medicine in Wangjing Hospital of China Academy of Chinese Medical Sciences from October 2014 to December 2019,among them,100 patients with ARCO stage Ⅲ and Ⅳ who were treated and followed up for at least 2 years between October 2014 and October 2017,and summarized the long-term efficacy of TCM in the treatment of "stay with collapse" patients with ONFH.160 patients in either side with ARCO stage Ⅲ or Ⅳ follow-up for at least 2 years were included and the related factors affecting the efficacy of TCM in the treatment of "stay with collapse" patients with ONFH were analyzed.from November 2017 to December 2019,30 patients with ARCO stage Ⅲ who were followed up for at least 2 years and had CT imaging data of the hip at a time interval of 1 year were enrolled,and to reveal the influence of bone structure changes on the whether success of TCM treatment of "stay with collapse" patients with ONFH by the team’s previous research on bone structure analysis method based on CT image 3D reconstruction simulation.1.Medium and long-term follow-up outcomes of TCM in the treatment of patients "stay with collapse" middle-advanced ONFH.This part adopted the method of retrospective cohort study to analyze clinical efficacy 100 cases of ARCO stage Ⅲ-Ⅳ ONFH patients who were followed up for at least 2 years in Wangjing Hospital of Chinese Academy of Chinese Medical Sciences during October 2014 to October 2017.The last follow-up time was December 2021,the follow-up was conducted in the form of a combination of outpatient and telephone electronic questionnaires,the main contents of the questionnaire included whether the affected joints were replaced with artificial joints and the replacement time,joint pain,flexion and walking distance.Hip joint replacement was used as the end-point outcome index,and the three clinical evaluation indexes of hip pain score,joint flexion function score,and walking distance score,three imaging evaluation indexes of X-ray femoral Bone morphology score,necrosis density score,and osteoarthritis degree score in "Evaluation Criteria for TCM Efficacy of Osteonecrosis of the femoral head(2019 Edition)" were as intermediate outcome indexes to evaluate the long-term follow-up outcome of ONFH after collapse treated by TCM.2.Analysis of the influencing factors on the efficacy of TCM in the treatment of patients "stay with collapse" ONFHThis part adopted the method of retrospective cohort study to analyze 160 patients on either side of ARCO stage Ⅲ-Ⅳ ONFH patients who were followed up for at least 2 years in Wangjing Hospital of Chinese Academy of Chinese Medical Sciences during October 2014 to October 2017.Excel table was used to summarize and record age,gender,body mass index(BMI),cause of disease,unilateral and bilateral onset,labor intensity classification,TCM syndrome type,ARCO staging,course of disease,hip flexion function,visual analog scale(VAS),walking distance,China-Japan Friendship Hospital(CJFH)classification,lesion size,degree of joint effusion.And the last follow-up time was October 2019,through a combination of outpatient and electronic questionnaire follow-up.Grouping was based on whether the participant received further hip-preserving surgical intervention or joint replacement therapy during the follow-up period(within 2 years).Patients who received further surgical interventions(including various hip-preserving surgeries and joint replacements)within 2 years were defined as the "disease aggravation" group,and those who did not receive the above further treatment within 2 years and still maintained TCM follow-up or observers were "disease stable" group.Univariate analysis was used to compare the differences in the above 15 indicators between the"disease aggravation" group and the "disease stable" group,the indexes with statistically significant differences(P≤0.05)were screened out and then multivariate binomial logistic regression analysis was performed to find out the factors affecting disease progression.The receiver operating characteristic curve(ROC)analysis was used to evaluate the performance of the study indicators in predicting whether the patient’s condition is worse within 2 years.3.To explore the regularity of bone structure changes of ONFH patients "stay with collapse" treated by TCM based on CT reconstruction of bone structureThis part adopted the method of retrospective cohort-study to retrospectively analyze the CT image data of 30 patients with ARCO stage III "stay with collapse"ONFH treated by TCM before and after treatment(the time interval between two CT scans was one year).To study objects in the follow-up period(2 years)whether to accept further hip surgery or joint replacement treatment as group basis,and patients who received further surgical interventions(including various hip-preserving surgeries and joint replacements)within 2 years were defined as the "disease aggravation" group,and those who did not receive the above further treatment within 2 years and still maintained TCM follow-up or observers were "disease stable" group.We used the medical image processing workstation Mimics 21.0 software,through the bone structure analysis method improved by our team in the early stage,to reconstruct the three-dimensional model of the femoral head in the two CT images of the two groups of patients before and after treatment.And based on the different gray values of CT,the soft tissue structure and sclerotic bone structure in the femoral head were reconstructed,and the volume changes of different bone structures before and after treatment were calculated.Using Materials 3-matic 11.0 software,the reconstructed femoral head before and after treatment was meshed,and the bone density of the femoral head was measured after material assignment.Nonparametric test was used to compare and analyze the sclerotic bone volume,soft tissue volume and femoral head density of the femoral head before and after treatment between the groups and within the group,which reveal the pattern of changes in bone structure in patients with ONFH after treatment with TCM.Results1.Medium and long-term follow-up outcomes of TCM in the treatment of ONFH patients "stay with collapse".A total of 100 patients were included in this study for analysis,including 74 males and 26 females,47 unilateral and 53 bilateral,95 hips in ARCO stage Ⅲ and 58 hips in ARCO stage Ⅳ.the patients in this group were followed up for an average of 4.5 years.27 hips underwent hip replacement in ARCO stage Ⅲ,and 19 hips underwent hip replacement in stage Ⅳ.The overall joint replacement rate was 30.06%(30 cases).The median survival time of ARCO Ⅲ stage hip joint was 84 months(95%CI:82.46-85.54),and the median survival time of ARCO Ⅳ stage hip joint was 82 months(95%CI:69.32-94.68),the difference was not statistically significant significance(χ2=2.024,P=0.16).Among the 30 patients who underwent joint replacement therapy,the median survival time of their own hip joint was 9.5 months,the shortest was 3 months,and the longest was 81 months.In terms of clinical efficacy evaluation,there was no significant difference in the VAS score of hip pain intensity before treatment between 70 patients(107 hips)without replacement and 30 patients(46 hips)with replacement[5(3)VS.5(2),Z=-0.52,P=0.61].There was no statistically significant difference in hip flexion[110(30)VS.100(23),Z=-1.59,P=0.11].There was statistically significant difference in walking distance[600(200)VS.500(200),Z=-2.89,P=0.004].The remaining 70 patients(107 hips)who did not undergo joint replacement had statistically significant differences in hip pain intensity before and after[5(3)VS.5(2),Z==-7.86,P<0.001].The mean value of hip flexion before treatment was 101±22.82 degrees,the median value was 110(30)degrees,the median value was 110(30)degrees after treatment,and the difference was statistically significant(Z=-2.61,P=0.009).the difference in hip flexion score before and after was statistically significant[2(3)VS.2(3),Z=-2.71,P=0.007].The average walking distance before treatment was 708±175.90 meters,the median was 600(200)meters,the walking distance was 735±216.05 meters after treatment,and the median was 800(200)meters.There was no significant difference in the walking distance score before and after treatment[4(2)VS.2(2),Z=-1.21,P=0.23].In terms of imaging efficacy evaluation,there was no significant difference in femoral head morphology scores between 70(107 hips)patients without replacement and 30(46 hips)patients with replacement before treatment[3(1)VS.3(1),Z=-0.59,P=0.56].There was no significant difference in the density score of femoral head necrosis[3(1)VS.3(1),Z=-0.35,P=0.72].The difference in hip osteoarthritis score was statistically significant[1(2)VS.3(1),Z=-7.40,P<0.001].The difference in the total score of imaging evaluation before treatment was statistically significant[6(2)VS.8(3),Z=-4.24,P<0.001].The remaining 70 patients(107 hips)without joint replacement showed a statistically significant difference in the femoral head morphology score[3(1)VS.3(1),Z=-5.14,P<0.001].The femoral head necrosis lesion density score was significantly different before and after treatment[3(1)VS.1(2),Z=-8.97,P<0.001].The osteoarthritis degree score was significantly different before and after treatment[1(2)VS.3(1),Z=-9.04,P<0.001].The total score of imaging efficacy was significantly different before and after treatment[6(2)VS.6(1),Z=-4.31,P<0.001].2.Analysis of the influencing factors on the efficacy of TCM in the treatment of patients "stay with collapse" ONFHA total of 160 patients were included in this part of the study,including 119(74.37%)males and 41(25.63%)females,which 73(45.63%)had progress within 2 years and the other 87(54.37%)had stability within 2 years.The results of univariate comparative analysis of the 15 included potential influencing factors showed that the patients in the progress group and the stability group had significantly different in unilateral or bilateral onset(χ2=37.99,P<0.001),BMI classification(χ2=23.72,P<0.001),hip Joint flexion(χ2=8.14,P=0.04),CJFH classification(χ2=53.77,P<0.001),lesion size(χ2=52.61,P<0.001),joint effusion size(χ2=38.38,P<0.001)these six indicators.While there was no significant difference in 9 indexes including age(47.75 VS.48.91,t=-0.57,P=0.57),gender composition(χ2=0.97,P=0.33),length of medical history(86 VS.84,Z=-0.61,P=0.54),TCM syndrome type(χ2=-0.98,P=0.61),etiological composition(x2=3.31,P=0.52),labor intensity classification(χ2=0.99,P=0.94),VAS score classification(x2=0.07,P=0.97),ARCO stage(χ2=0.41,P=0.94),and walking distance(χ2=2.59,P=0.46).The results of multivariate binomial logistic regression analysis showed that patient’s BMI classification,unilateral or bilateral disease,CJFH classification,lesion size,joint effusion classification affect whether the patient’s condition was aggravated.Compared with patients with BMI<24,overweight patients(24≤BMI<28,P=0.018,OR=8.66,95%CI=1.46-51.53)and obese patients(BMI≥28,P=0.001,OR=32.28,95%CI=4.55-229.03),the risk of progression increased gradually.In terms of disease side,compared with patients with unilateral disease,patients with bilateral disease had an approximately 17-fold higher risk of progression(P<0.001,OR=17.89,95%CI=4.47-71.65).On the CJFH classification,the risk of progression in patients with L3 type necrotic band penetrating the entire cortex and bone marrow of the three-column structure of the femoral head was about 23 times of M type patients(P=0.003,OR=23.11,95%CI=2.94-181.86).In terms of lesion size,patients with large lesions(necrosis area≥30%)had approximately 7fold higher risk of progression than small lesions(necrosis area<15%)(P=0.008,OR=7.19,95%CI=1.66-31.17).In terms of hip joint effusion,the size of the effusion was proportional to the progression,and compared with no joint effusion(grade 0),grade Ⅰ joint effusion(P=0.09,OR=5.38,9 5%CI=0.77-37.78),grade Ⅱ joint effusion(P=0.01,OR=21.42,95%CI=2.09-219.51),grade Ⅲ joint effusion(P=0.002,OR=23.14,95%CI=3.13-171.23),the risk of progression increased sequentially from approximately 5fold to approximately 23fold.The regression equation established by combining the patient’s BMI classification,onset side,CJFH classification,lesion size,joint effusion classification and other indicators has a satisfactory performance in predicting progress(AUC=0.95).3.To explore the regularity of bone structure changes of ONFH patients "stay with collapse" treated by TCM based on CT reconstruction of bone structureIn this part of the study,30 patients(30 hips)with "stay with collapse" ONFH treated by dialectical treatment of TCM were included,including 23 males and 7 females.15 patients in the "disease stable" group and 15 in the "disease aggravation"group.These patients with an average age of 42.60±12.92 years old,the average disease duration was 38.30±8.29 months.The average disease duration in the "disease stable" group was 34.33±7.67 months.The average disease duration in the "disease aggravation" group was 42.27±7.07 months.Under the visual comparison with the eye,the outline of the normal femoral head is smooth and round,the femoral head contains almost no sclerotic bone structure,and the soft tissue structural components are evenly distributed and almost fill the entire femoral head.In the cases of ONFH,whether in the "disease aggravation" group or the "disease stable" group,the outline of the femoral head was distorted and deformed to varying degrees,lost its smooth and rounded state.The appearance of sclerotic bone structures in the femoral head to varying degrees,and the soft tissue structure shows a trend of decreasing distribution.The two types of bone structures presented an irregular,discontinuous arrangement.After treatment,the content of sclerotic bone structure in the femoral head increased compared with before treatment,while the content of soft tissue showed signs of decrease.The content of sclerotic bone structure in the femoral head did not change significantly in the "disease aggravation" group,but the content of soft tissue increased sign.Compared with before treatment,the sclerotic bone volume increased in all patients after treatment(Z=-4.41,P<0.001),while the soft tissue volume decreased as a whole,but the difference was not statistically significant(Z=-1.68,P=0.094).In the comparison of the bone mineral density of the femoral head,the overall bone mineral density increased after treatment,and the difference was statistically significant(Z=-4.76,P<0.001).Comparison of different bone structure and femoral head density before and after treatment between groups,before treatment,the sclerotic bone volume in the "disease stable" group was smaller than that in the "disease aggravation" group(Z=-2.38,P=0.017),the soft tissue volume of the "disease stable"group was larger than that of the "disease aggravation" group(Z=-3.21,P=0.001).There was no significant difference in the volume of sclerotic bone between the two groups after treatment(Z=-1.26,P=0.206).The difference in soft tissue volume is also not obvious(Z=-1.22,P=0.221).In the comparison of bone mineral density of the femoral head,there was no significant difference between the "disease stable" group and the "disease aggravation" group before treatment(Z=-1.72,P=0.085)and after treatment(Z=-1.76,P=0.078).In terms of intra-group comparison of different bone structure and femoral head density before and after treatment,the "disease stable" group(Z=-3.41,P=0.001)and the "disease aggravation" group(Z=-2.56,P=0.011)compared differences are statistically significant before and after treatment in sclerotic bone volume.In terms of soft tissue volume comparison,the difference between the "disease stable" group(Z=-3.41,P=0.001)and the "disease aggravation" group(Z=-3.24,P=0.001)before and after treatment was statistically significant.In the comparison of the bone mineral density of the femoral head,the difference between the stable group(Z=-3.41,P=0.001)and the aggravation group(Z=-3.35,P=0.001)before and after treatment was statistically significant.Comparison between groups before and after treatment on the bone structure of the femoral head and the change in BMD of the femoral head,In the comparison of changes in sclerotic bone volume,the patients in the "disease stable" group were significantly higher than those in the "disease aggravation" group(Z=-4.66,P<0.001).In the comparison of the soft tissue volume,the soft tissue volume of the patients in the "disease stable" group decreased after treatment,while the patients in the "disease aggravation" group increase(Z=-4.67,P<0.001).Compared with the changes in the bone mineral density of the femoral head,both groups increased after treatment,but there was no significant difference in the changes(Z=-0.64,P=0.52).Conclusions1.The treatment of middle-advanced ONFH with TCM can make about two-thirds of the patients "stay with collapse",which has the therapeutic effect of delaying or avoiding joint replacement,reducing pain and maintaining joint function.2.Body mass index overweight,bilateral onset,large lesions(necrosis area>30%),L3 type in CJFH classification,and joint effusion are risk factors for "progression" in ONFH patients "stay with collapse" treated by TCM.3.In the treatment of ONFH "stay with collapse" by TCM,the change rule of bone structure follows the general rule that the volume of sclerotic bone increases gradually with the increase of the course of the disease,the volume of soft tissue gradually decreases,and the density of the femoral head gradually increases. |
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