Bushen Huoxue Prescription Regulates PINP and β-CTX in Treatment of Femoral Head Necrosis with Syndrome of Liver and Kidney Deficiency / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic mechanism of Bushen Huoxue prescription from the perspective of bone metabolism by observing the clinical efficacy of this prescription in treating femoral head necrosis （ONFH， syndrome of liver and kidney deficiency） and its influences on bone metabolism indexes： N-terminal propeptide （PINP） and β-collagen degradation product （β-CTX）. MethodSixty-six ONFH patients with the syndrome of liver and kidney deficiency in Zhengzhou Traditional Chinese Medicine Hospital of Orthopedics from December 2021 to September 2022 were selected. The patients were randomized into an experimental group and a control group by the parallel control method， with 33 patients in each group. The experimental group received Bushen Huoxue prescription orally， while the control group received Xianlinggubao Capsules orally， with a treatment cycle of 6 months. The visual analogue scale （VAS） score， Harris score， Association Research Circulation Osseous （ARCO） staging， imaging changes， quantitative scores of TCM symptoms， and serum levels of PINP and β-CTX were determined before and after treatment. The occurrence of adverse events and reactions was recorded. ResultThe total response rate in the experimental group was 83.87% （26/31）， which was higher than that （68.75%， 22/32） in the control group （Z=-2.096， P<0.05）. After treatment， the single and total scores of TCM symptoms， VAS score， and β-CTX level decreased in the two groups （P<0.05）. Moreover， the decreases in the scores of hip pain， lower limb mobility， soreness of waist and knees， and lower limb flaccidity， total score of TCM symptoms， VAS score， and β-CTX level in the experimental were larger than those in the control group （P<0.05）. After treatment， the imaging results showed no significant improvement in the two groups. The Harris score and PINP level in both groups increased after treatment （P<0.05）， and the increases were more obvious in the experimental group than in the control group （P<0.05）. No serious adverse event or adverse reaction appeared during the observation period. ConclusionBushen Huoxue prescription can relieve pain and TCM symptoms and improve the hip joint function in treating ONFH patients with the syndrome of liver and kidney deficiency. It can inhibit the development of ONFH， increase PINP， and decrease β-CTX. No obvious side effect appears during the clinical observation period， which shows that Bushen Huoxue prescription has good safety.

Role and mechanism of macrophage-mediated osteoimmune in osteonecrosis of the femoral head / 中国修复重建外科杂志

OBJECTIVE@#To summarize the research progress on the role of macrophage-mediated osteoimmune in osteonecrosis of the femoral head (ONFH) and its mechanisms.@*METHODS@#Recent studies on the role and mechanism of macrophage-mediated osteoimmune in ONFH at home and abroad were extensively reviewed. The classification and function of macrophages were summarized, the osteoimmune regulation of macrophages on chronic inflammation in ONFH was summarized, and the pathophysiological mechanism of osteonecrosis was expounded from the perspective of osteoimmune, which provided new ideas for the treatment of ONFH.@*RESULTS@#Macrophages are important immune cells involved in inflammatory response, which can differentiate into classically activated type (M1) and alternatively activated type (M2), and play specific functions to participate in and regulate the physiological and pathological processes of the body. Studies have shown that bone immune imbalance mediated by macrophages can cause local chronic inflammation and lead to the occurrence and development of ONFH. Therefore, regulating macrophage polarization is a potential ONFH treatment strategy. In chronic inflammatory microenvironment, inhibiting macrophage polarization to M1 can promote local inflammatory dissipation and effectively delay the progression of ONFH; regulating macrophage polarization to M2 can build a local osteoimmune microenvironment conducive to bone repair, which is helpful to necrotic tissue regeneration and repair to a certain extent.@*CONCLUSION@#At present, it has been confirmed that macrophage-mediated chronic inflammatory immune microenvironment is an important mechanism for the occurrence and development of ONFH. It is necessary to study the subtypes of immune cells in ONFH, the interaction between immune cells and macrophages, and the interaction between various immune cells and macrophages, which is beneficial to the development of potential therapeutic methods for ONFH.

Modified Dunn Technique for Unstable Slipped Capital Femoral Epiphysis: A Midterm Single Center Experience / Técnica de Dunn modificada no escorregamento da epífise femoral proximal com instabilidade: Experiência unicêntrica de médio prazo

Abstract Objective To evaluate the safety and reproducibility of the surgery for unstable slipped capital femoral epiphysis (SCFE) through the modified Dunn technique in a single center cohort from Brazil. Methods We retrospectively analyzed a cohort of patients submitted to this procedure by a single surgeon who was a hip preservation specialist. Demographic data and radiographic angles were evaluated for the relative risk (RR) of avascular necrosis (AVN) using a log-binomial regression model with simple and random effects. Results Among the 30 patients (30 hips) with a mean age of 11.79 years at the time of the operation, there were 17 boys and 18 left hips, which were operated on in a mean of 11.5 days after the slip. The mean follow-up was of 38 months. The preoperative Southwick angle averaged 60.69° against 4.52° postoperatively (p< 0.001). A larger preoperative slip angle was associated with the development of AVN (RR: 1.05; 95% confidence interval [95%CI]: 1.02-1.07; p< 0.01). The overall AVN rate was of 26.7%. Function was good or excellent in 86% of uncomplicated hips, and poor in 87.5% of the partients who developed AVN, as graded by the Harris Hip Score. There was no statistical relationship between epiphyseal bleeding and AVN development (p= 0.82). Conclusion The modified Dunn technique is associated with restoration of the femoral alignment and function after unstable SCFE, when uncomplicated. Moreover, it was shown to be reproducible in our population, with a rate of 26% of femoral head necrosis.

Resumo Objetivo Avaliar a segurança e a reprodutibilidade da cirurgia para escorregamento da epífise femoral proximal (EEPF) com instabilidade por meio da técnica de Dunn modificada em uma coorte unicêntrica no Brasil. Métodos Analisamos de forma retrospectiva uma coorte de pacientes submetidos a esse procedimento por um único cirurgião especialista em preservação do quadril. Avaliamos os dados demográficos e os ângulos radiográficos quanto ao risco relativo (RR) de necrose avascular (NAV) por meio do modelo de regressão log-binomial com efeitos simples e aleatórios. Resultados Entre os 30 pacientes (30 quadris) com idade média de 11,79 anos no momento da cirurgia, havia 17 meninos e 18 quadris esquerdos. O procedimento ocorreu em média 11,5 dias após o escorregamento. O tempo médio de acompanhamento foi de 38 meses. O ângulo de Southwick pré-operatório foi, em média, de 60,69° contra 4,52° após o procedimento (p< 0,001). O maior ângulo de escorregamento pré-operatório foi associado ao desenvolvimento de NAV (RR: 1,05; intervalo de confiança de 95% [IC95%]: 1,02-1,07; p< 0,01). A frequência geral de NAV foi de 26,7%. De acordo com a Escala de Quadril de Harris (Harris Hip Score), a função foi boa ou excelente em 86% dos quadris sem complicações, e ruim em 87,5% dos casos com NAV. Não houve relação estatística entre sangramento epifisário e desenvolvimento de NAV (p= 0,82). Conclusão A técnica de Dunn modificada restaura o alinhamento femoral e a função articular após o EEPF com instabilidade na ausência de complicações. Além disso, mostrou-se passível de reprodução em nossa população, com frequência de necrose da cabeça femoral de 26%.

Refixation of the Excised Acetabular Labrum can Affect the Structural Changes of Cartilage Surface in the Hip Joint / La Refijación del Labrum Acetabular Extirpado Puede Afectar los Cambios Estructurales de la Superficie del Cartílago en la Articulación Coxal

SUMMARY: Refixation of the damaged acetabular labrum is a method of surgical treatment of the hip joint that can promote the repair of joint function after injury and prevent premature osteoarthritis. We sought to determine the condition of the hip joint in rabbits 4 months after excision of the acetabular labrum and the condition of the joint after labral refixation. The articular cartilage of the femoral head and acetabulum was examined by histological methods, multipoint measurement of cartilage thickness, and the ratio between cartilage matrix and chondrocytes lacunae, and the condition of cartilage according to the OARSI grading scale was carried out. On this model, a correlation analysis was performed between the results of the OARSI grading scale and the data of linear morphometry. All these parameters made it possible to better assess changes in articular cartilage. The ratio between matrix and chondrocyte lacunae turned out to be a method that allows establishing early cartilage damage when erosion, fibrosis or deformation did not occur. We found significant differences between the condition of the cartilage after exicion of acetabular labrum and after labral refixation, which give hope to confirm that this surgical technique can delay or prevent progressive changes in the cartilage of the damaged hip joint.

La refijación del labrum acetabular dañado es un método de tratamiento quirúrgico de la articulación coxal, que puede promover la reparación de la función articular después de una lesión y prevenir la osteoartritis prematura. Intentamos determinar el estado de la articulación coxal en conejos de 4 meses después de la escisión del labrum acetabular y observar el estado de la articulación después de la refijación del labrum. El cartílago articular de la cabeza femoral y el acetábulo se examinó por métodos histológicos, se midió a través de multipunto el grosor del cartílago y se realizó la relación entre la matriz del cartílago y las lagunas de condrocitos, y se llevó a cabo la condición del cartílago según la escala de clasificación OARSI. Sobre este modelo se realizó un análisis de correlación entre los resultados de la escala de calificación OARSI y los datos de la morfometría lineal. Todos estos parámetros permitieron evaluar mejor los cambios en el cartílago articular. La relación entre la matriz y las lagunas de condrocitos resultó ser un método que permite establecer temprano el daño del cartílago cuando no se presentó erosión, fibrosis o deformación. Encontramos diferencias significativas entre la condición del cartílago después de la extirpación del labrum acetabular y después de la refijación del labrum, lo que da la esperanza de confirmar que esta técnica quirúrgica puede retrasar o prevenir cambios progresivos en el cartílago de la articulación coxal dañada.

Risk Factors of avascular Osteonecrosis of the Femoral Head in Children at the National ReferenceCenter for Sickle Cell Disease in Brazzaville, Congo

Introduction: The avascular osteonecrosis of the femoral head (AOFH) is a common complication of sickle cell disease (SCD). It exposes to lameness and sometimes to a very debilitating handicap. It is a source of desocialization, particularly in developing countries where prosthetic surgery remains inaccessible to the majority. This survey aimed to identify the risk of occurence AOFH. Materials and Methods: It was a case-control study carried between october 2017 and september 2021 at the National Reference Center for SCD « Antoinette Sassou Nguesso » in Brazzaville. It concerned 31 children with clinical and radiographic signs of AOFH. Clinical (age at diagnosis of SCD, frequency of vasoocclusive crises and hospitalization for vasoocclusive crises, number of blood transfusion) as well as hematological examination (blood count in the intercritical period) and hydroxyurea treatment were compared with those of 62 children with no clinical and radiographic signs of AOFH. The chi2 statistical test and the odds ratio were used for the comparison (P ˂ 0.05).Results: The sex ratio was 1.38 versus 0.93 (p = 0.50). The mean age of diagnostic of SCD was 3.76 ± 2.56 years versus 3.94 ± 2.01 years (p = 0.81). Logistic regression showed that SCD children with AOFH had a significantly higher rate of annual frequency of VOC (4.16 1.18 vs 2.91 1.68; P = 0.015), annual frequency of hospitalization for VOC (3.741.65 vs 1.451.28; P = 0.000) and number of blood transfusions (3.38 ± 2.69 vs 2.42 ± 2.32; P = 0.03).Conclusion: Emphasis should be placed on the prevention and early management of acute complications of SCD. The role of hydroxyurea should be clarified by further work.

Pipkin Type-II Femoral Head Fracture: A Biomechanical Evaluation by the Finite-Element Method / Fratura da cabeça femoral de tipo II de Pipkin: Avaliação biomecánica pelo método de elementos finitos

Abstract Objective To evaluate the biomechanical capacity of two forms of fixation for Pipkin type-II fractures, describing the vertical fracture deviation, the maximum and minimum principal stresses, and the Von Mises equivalent stress in the syntheses used. Materials and Methods Two internal fasteners were developed to treat Pipkin type-II fractures through finite elements: a 3.5-mm cortical screw and a Herbert screw. Under the same conditions, the vertical fracture deviation, the maximum and minimum principal stresses, and the Von Mises equivalent stress in the syntheses used were evaluated. Results The vertical displacements evaluated were of 1.5mm and 0.5mm. The maximum principal stress values obtained in the upper region of the femoral neck were of 9.7 KPa and 1.3 Kpa, and the minimum principal stress values obtained in the lower region of the femoral neck were of-8.7 KPa and -9.3 KPa. Finally, the peak values for Von Mises stress were of 7.2 GPa and 2.0 GPa for the fixation models with the use of the 3.5-mm cortical screw and the Herbert screw respectively. Conclusion The fixation system with the Herbert screw generated the best results in terms of reduction of vertical displacement, distribution of the maximum principal stress, and the peak Von Mises equivalent stress, demonstrating mechanical superiority compared to that of the 3.5-mm cortical screw in the treatment of Pipkin type-II fractures.

Resumo Objetivo Avaliar a capacidade biomecánica de duas formas de fixação de fraturas tipo II de Pipkin descrevendo o desvio da fratura no sentido vertical, as tensões máxima e mínima principais, e a tensão equivalente de Von Mises nas sínteses utilizadas. Materiais e Métodos Dois fixadores internos foram desenvolvidos para tratar a fratura tipo II de Pipkin por meio de elementos finitos: parafuso cortical de 3,5 mm e parafuso de Herbert. Sob as mesmas condições, foram avaliados o desvio da fratura no sentido vertical, as tensões máxima e mínima principais, e a tensão equivalente de Von Mises nas sínteses utilizadas. Resultados Os deslocamentos verticais avaliados foram de 1,5 mm e 0,5 mm. Os valores de tensão máxima obtidos na região superior do colo femoral foram de 9,7 KPa e 1,3 KPa, e os valores de tensão mínima obtidos na região inferior do colo femoral foram de -8,7KPa e -9,3 KPa. Por fim, os valores de pico da tensão equivalente de Von Misesforam de 7,2 GPa e2,0 GPa paraosmodelos de fixação com o uso do parafuso cortical de 3,5 mm e do parafuso de Herbert, respectivamente. Conclusão Osistema de fixação com parafuso de Herbert gerou os melhores resultados em termos de redução do deslocamento vertical, distribuição da tensão máxima e do pico da tensão equivalente de Von Mises, o que demonstra sua superioridade mecânica comparada à do parafuso cortical de 3,5 mm no tratamento da fratura tipo II de Pipkin.

Investigation on Mechanisms of Osteoking Against Four Types of Bone Injury Diseases Based on Heterogeneous Information Network with Concept of "Treating Different Diseases with an Identical Treatment" / 中国实验方剂学杂志

ObjectiveTo elucidate the mechanism of Osteoking against fracture， femoral head necrosis， osteoarthritis， and lumbar disc herniation by integrating heterogeneous information network mining and experimental validation. MethodOn the basis of the disease-related database and transcriptome expression profiling dataset， as well as the ETCM database， the gene sets related to four target diseases and the candidate target spectrum of Osteoking were obtained through the integration and analysis of bioinformatics data， and a "disease-syndrome-formula-target-pathway-effect" heterogeneous information network was constructed. In addition， by functional enrichment analysis， the core targets of Osteoking in interfering with the imbalance network of four kinds of bone injury diseases， the biological pathways involved， and the corresponding clinical symptoms were screened， and they were verified in animal experiments. ResultHeterogeneous information network mining indicates that Osteoking may commonly reverse the imbalance networks of fracture， femoral head necrosis， osteoarthritis， and lumbar disc herniation via regulating cell function and activity， inhibiting inflammatory response， reducing bone destruction， and improving the immune function of the body by modulating relevant core candidate targets such as RAC-alpha serine/threonine-protein kinase （Akt1）， catenin beta-1 （CTNNB1）， epidermal growth factor receptor （EGFR）， heat shock protein 90-alpha （HSP90AA1）， and phosphatidylinositol 3-kinase catalytic subunit alpha isoform （PI3KCA）， as well as related biological pathways such as phosphatidylinositide 3-kinases/protein kinase B （PI3K/Akt）， janus kinase/signal transducer and activator of transcription （JAK/STAT）， tumor necrosis factor （TNF）， nuclear factor kappa-B （NF-κB）， and Toll-like receptors. In particular， Osteoking may improve the blood supply of the fracture end by regulating blood circulation at the target site of the disease， and it may maintain the balance of bone metabolism by regulating hormone-related pathways to promote fracture healing. In addition， Osteoking may relieve lipid metabolism disorders by targeting and regulating lipid-related pathways， accelerate bone formation and bone repair， and delay the progression of femoral head necrosis. Osteoking may relieve the symptoms of pain by acting on neurological pathways to reduce local nociceptive stimulation in patients with osteoarthritis and lumbar disc herniation. Further experimental validation demonstrates that the PI3K/Akt signaling pathway is the most significantly enriched pathway for the key network targets of Osteoking for the four diseases. The candidate target of Osteoking may have the strongest association with the network of fracture-related genes. Therefore， this study chooses fracture as the target disease to verify the efficacy of Osteoking. The results show that Osteoking can accelerate bone formation and promote fracture healing by inhibiting the activation of the PI3K/Akt signaling axis. ConclusionThe study shows that the main mechanism of "treating different diseases with an identical treatment" of four bone injury diseases with Osteoking involves cell function regulation and immune inflammation-related signaling pathways. Further experimental validation identifies that the PI3K/Akt signaling axis may be one of the key pathways of Osteoking to promote bone regeneration， bone reconstruction， and bone metabolism homeostasis.

Primary repair for concurrent bilateral intertrochanteric fracture and femoral head necrosis with prolonged shank biologic total hip replacement: A case report and surgical techniques / 中华创伤杂志(英文版)

For the treatment of an intertrochanteric fracture combined with femoral head necrosis in middle-age patients, it has been controversial whether to perform fracture reduction and fixation first then total hip replacement, or direct total hip replacement. We present a rare case of 53-year-old male patient suffered from bilateral intertrochanteric fracture caused by a road traffic injury. The patient had a history of femoral head necrosis for eight years, and the Harris score was 30. We performed total hip replacement with prolonged biologic shank prostheses for primary repair. One year after the surgery, nearly full range of motion was achieved without instability (active flexion angle of 110°, extension angle of 20°, adduction angle of 40°, abduction angle of 40°, internal rotation angle of 25°, and external rotation angle of 40°). The Harris score was 85. For the middle-aged patient with unstable intertrochanteric fractures and osteonecrosis of the femoral head, we can choose primary repair for concurrent bilateral intertrochanteric fracture and femoral head necrosis with prolonged shank biologic total hip replacement.

Repair Mechanism of Jianpi Huogu Prescription on Vascular Injury in Alcohol-induced Osteonecrosis of Femoral Head Based on VEGF/VEGFR2/PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

MethodIn the experiment， 46% vol Red Star Erguotou （10 mL·kg·d-1） was used to establish the AONFH rat model， and the intervention effect of JPHGP at different doses （2.5， 5.0， 10.0 g·kg-1） was observed. Jiangusheng pill （JGS， 1.53 g·kg-1） was selected as the positive control. After 8 weeks of administration， the bone histomorphometry of the femoral head was analyzed by Micro-CT imaging， and the area of medullary microvessels in the femoral head was detected by ink perfusion. The pathological change was observed by hematoxylin and eosin （HE） staining. The protein expressions of Platelet endothelial cell adhesion molecule-1 （CD31）， VEGF， VEGFR2， PI3K， phosphor-Akt （p-Akt） and phosphatase and Tensin homologue deleted on chromosome 10 （PTEN） in the femoral head were determined by immunohistochemistry and Western blot. ResultCompared with normal group， the model group presented the fracture and thinning of trabeculae in the femoral head， increased empty bone lacunae， and elevated number and diameter of adipocytes （P<0.01）. Micro-CT imaging revealed a decrease in bone mineral density （BMD）， bone volume fraction （BV/TV）， trabecular thickness （Tb.Th） and trabecular number （Tb.N） （P<0.05， P<0.01） while an increase in bone surface-to-volume ratio （BS/BV） and trabecular separation （Tb.Sp） （P<0.01）. The results of ink perfusion showed that the area of medullary microvessels in the femoral head was reduced （P<0.01）. Compared with model group， JPHGP lowered the empty bone lacunae rate as well as the number and diameter of adipocytes in the femoral head of AONFH rats. Micro-CT imaging indicated that JPHGP low-dose group had elevated BV/TV， Tb.Th and Tb.N （P<0.05， P<0.01） while decreased BS/BV （P<0.01）， and there was an upward trend in BMD while a downward trend in Tb.Sp， but without statistical difference. In addition， JPHGP medium- and high-dose groups had a rise in BMD， BV/TV， Tb.Th and Tb.N （P<0.05， P<0.01）， a decrease in BS/BV and Tb.Sp （P<0.05， P<0.01） and enlarged area of medullary microvessels in the femoral head （P<0.05， P<0.01）. The expressions of CD31， VEGF， VEGFR2， PI3K， p-Akt in the model group were lower than those in the normal group （P<0.01）， and after medium and high doses of JPHGP treatment， the expressions of CD31， PI3K and p-Akt in the femoral head of rats were up-regulated （P<0.01） while the protein expression of PTEN was down-regulated （P<0.01）. Moreover， JPHGP up-regulated the expressions of VEGF and VEGFR2 （P<0.05， P<0.01）. ConclusionJPHGP can repair the vascular injury in AONFH， and its mechanism may be related to the activation of VEGF/VEGFR2/PI3K/Akt signaling pathway. This study provides certain scientific basis and reference for the clinical application of JPHGP. ObjecctiveTo observe the repair effect of Jianpi Huogu prescription （JPHGP） on vascular injury in experimental alcohol-induced osteonecrosis of femoral head （AONFH）， and to explore its mechanism based on vascular endothelial growth factor （VEGF）/VEGFR2/phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway.

Visual and quantitative assessment of the effectiveness of non-vascularized bone grafting in osteonecrosis of the femoral head via CT-based radiomics and clinical data / 中国修复重建外科杂志

OBJECTIVE@#To investigate the value of CT-based radiomics and clinical data in predicting the efficacy of non-vascularized bone grafting (NVBG) in hip preservation, and to construct a visual, quantifiable, and effective method for decision-making of hip preservation.@*METHODS@#Between June 2009 and June 2019, 153 patients (182 hips) with osteonecrosis of the femoral head (ONFH) who underwent NVBG for hip preservation were included, and the training and testing sets were divided in a 7∶3 ratio to define hip preservation success or failure according to the 3-year postoperative follow-up. The radiomic features of the region of interest in the CT images were extracted, and the radiomics-scores were calculated by the linear weighting and coefficients of the radiomic features after dimensionality reduction. The clinical predictors were screened using univariate and multivariate Cox regression analysis. The radiomics model, clinical model, and clinical-radiomics (C-R) model were constructed respectively. Their predictive performance for the efficacy of hip preservation was compared in the training and testing sets, with evaluation indexes including area under the curve, C-Index, sensitivity, specificity, and calibration curve, etc. The best model was visualised using nomogram, and its clinical utility was assessed by decision curves.@*RESULTS@#At the 3-year postoperative follow-up, the cumulative survival rate of hip preservation was 70.33%. Continued exposure to risk factors postoperative and Japanese Investigation Committee (JIC) staging were clinical predictors of the efficacy of hip preservation, and 13 radiomic features derived from least absolute shrinkage and selection operator downscaling were used to calculate Rad-scores. The C-R model outperformed both the clinical and radiomics models in predicting the efficacy of hip preservation 1, 2, 3 years postoperative in both the training and testing sets ( P<0.05), with good agreement between the predicted and observed values. A nomogram constructed based on the C-R model showed that patients with lower Rad-scores, no further postoperative exposure to risk factors, and B or C1 types of JIC staging had a higher probability of femoral survival at 1, 2, 3 years postoperatively. The decision curve analysis showed that the C-R model had a higher total net benefit than both the clinical and radiomics models with a single predictor, and it could bring more net benefit to patients within a larger probability threshold.@*CONCLUSION@#The prediction model and nomogram constructed by CT-based radiomics combined with clinical data is a visual, quantifiable, and effective method for decision-making of hip preservation, which can predict the efficacy of NVBG before surgery and has a high value of clinical application.

Analysis of incidence and clinical characteristics of osteonecrosis of femoral head in patients with systemic lupus erythematosus treated with glucocorticoid: A descriptive study based on a prospective cohort / 中国修复重建外科杂志

OBJECTIVE@#To describe the disease characteristics of osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE) who experiencing prolonged glucocorticoid (GC) exposure.@*METHODS@#Between January 2016 and June 2019, 449 SLE patients meeting the criteria were recruited from multiple centers. Hip MRI examinations were performed during screening and regular follow-up to determine the occurrence of ONFH. The cohort was divided into ONFH and non-ONFH groups, and the differences in demographic baseline characteristics, general clinical characteristics, GC medication information, combined medication, and hip clinical features were compared and comprehensively described.@*RESULTS@#The age at SLE diagnosis was 29.8 (23.2, 40.9) years, with 93.1% (418 cases) being female. The duration of GC exposure was 5.3 (2.0, 10.5) years, and the cumulative incidence of SLE-ONFH was 9.1%. Significant differences ( P<0.05) between ONFH and non-ONFH groups were observed in the following clinical characteristics: ① Demographic baseline characteristics: ONFH group had a higher proportion of patients with body mass index (BMI)<20 kg/m 2 compared to non-ONFH group. ② General clinical characteristics: ONFH group showed a higher proportion of patients with cutaneous and renal manifestations, positive antiphospholipid antibodies (aPLs) and anticardiolipin antibodies, severe SLE patients [baseline SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥15], and secondary hypertension. Fasting blood glucose in ONFH group was also higher. ③ GC medication information: ONFH group had higher initial intravenous GC exposure rates, duration, cumulative doses, higher cumulative GC doses in the first month and the first 3 months, higher average daily doses in the first 3 months, and higher proportions of average daily doses ≥15.0 mg/d and ≥30.0 mg/d, as well as higher full-course average daily doses and proportion of full-course daily doses ≥30.0 mg/d compared to non-ONFH group. ④ Combined medications: ONFH group had a significantly higher rate of antiplatelet drug use than non-ONFH group. ⑤ Hip clinical features: ONFH group had a higher proportion of hip discomfort or pain and a higher incidence of hip joint effusion before MRI screening than non-ONFH group.@*CONCLUSION@#The incidence of ONFH after GC exposure in China's SLE population remains high (9.1%), with short-term (first 3 months), medium-to-high dose (average daily dose ≥15 mg/d) GC being closely associated with ONFH. Severe SLE, low BMI, certain clinical phenotypes, positive aPLs, and secondary hypertension may also be related to ONFH.

A novel lateral classification of osteonecrosis of femoral head based on CT recons-truction of necrotic area and its clinical verification / 中国修复重建外科杂志

OBJECTIVE@#To analyze the femoral head collapse and the operation of osteonecrosis of the femoral head (ONFH) in different Japanese Investigation Commitee (JIC) types, in order to summarize the prognostic rules of each type of ONFH, and explore the clinical significance of CT lateral subtypes based on reconstruction of necrotic area of C1 type and verify their clinical effect.@*METHODS@#A total of 119 patients (155 hips) with ONFH between May 2004 and December 2016 were enrolled in the study. The total hips consisted of 34 hips in type A, 33 in type B, 57 in type C1, and 31 in type C2, respectively. There was no significant difference in age, gender, affected side, or type of ONFH of the patients with differenct JIC types ( P>0.05). The 1-, 2-, and 5-year femoral head collapse and operation of different JIC types were analyzed, as well as the survival rate (with femoral head collapse as the end point) of hip joint between different JIC types, hormonal/non-hormonal ONFH, asymptomatic and symptomatic (pain duration >6 months or ≤6 months), and combined preserved angle (CPA) ≥118.725° and CPA<118.725°. JIC types with significant differences in subgroup surgery and collapse and with research value were selected. According to the location of the necrotic area on the surface of the femoral head, the JIC classification was divided into 5 subtypes in the lateral CT reconstruction, and the contour line of the necrotic area was extracted and matched to the standard femoral head model, and the necrosis of the five subtypes was presented by thermography. The 1-, 2-, and 5-year outcomes of femoral head collapse and operation in different lateral subtypes were analyzed, and the survival rates (with collapse of the femoral head as the end point) between CPA≥118.725° and CPA<118.725° hip in patients with this subtype were compared, as well as the survival rates of different lateral subtypes (with collapse and surgery as the end points, respectively).@*RESULTS@#The femoral head collapse rate and operation rate in the 1-, 2-, and 5-year were significantly higher in patients with JIC C2 type than in patients with other hip types ( P<0.05), while in patients with JIC C1 type than in patients with JIC types A and B ( P<0.05). The survival rate of patients with different JIC types was significantly different ( P<0.05), and the survival rate of patients with JIC types A, B, C1, and C2 decreased gradually. The survival rate of asymptomatic hip was significantly higher than that of symptomatic hip, and the survival rate of CPA≥118.725° was significantly higher than that of CPA<118.725° ( P<0.05). The lateral CT reconstruction of type C1 hip necrosis area was selected for further classification, including type 1 in 12 hips, type 2 in 20 hips, type 3 in 9 hips, type 4 in 9 hips, and type 5 in 7 hips. There were significant differences in the femoral head collapse rate and the operation rate among the subtypes after 5 years of follow-up ( P<0.05). The collapse rate and operation rate of types 4 and 5 were 0; the collapse rate and operation rate of type 3 were the highest; the collapse rate of type 2 was high, but the operation rate was lower than that of type 3; the collapse rate of type 1 was high, but the operation rate was 0. In JIC type C1 patients, the survival rate of the hip joint with CPA≥118.725° was significantly higher than that with CPA<118.725° ( P<0.05). In the follow-up with femoral head collapse as the end point, the survival rates of types 4 and 5 were all 100%, while the survival rates of types 1, 2, and 3 were all 0, and the difference was significant ( P<0.05). The survival rate of types 1, 4, and 5 was 100%, of type 3 was 0, and of type 2 was 60%, showing significant difference ( P<0.05).@*CONCLUSION@#JIC types A and B can be treated by non-surgical treatment, while type C2 can be treated by surgical treatment with hip preservation. Type C1 was classified into 5 subtypes by CT lateral classification, type 3 has the highest risk of femoral head collapse, types 4 and 5 have low risk of femoral head collapse and operation, type 1 has high femoral head collapse rate but low risk of operation; type 2 has high collapse rate, but the operation rate is close to the average of JIC type C1, which still needs to be further studied.

Active Components in Chinese Medicinal Herbs Regulate Osteogenic Signaling Pathway in Treatment of Steroid-induced Osteonecrosis of Femoral Head： A Review / 中国实验方剂学杂志

As a threat to human health， steroid-induced osteonecrosis of femur head is a common refractory orthopedic disease mainly caused by glucocorticoids， with poor prognosis and unclear pathogenesis. Osteogenesis-associated signaling pathways play an important role in bone formation. Glucocorticoid-induced abnormal activation and transport of these signaling pathways lead to abnormal differentiation of bone marrow mesenchymal stem cells， dysfunction of bone metabolism， and osteogenesis disorders， which may be the main reasons for the occurrence and development of steroid-induced osteonecrosis of femur head. Bone formation and remodeling need the participation of bone marrow mesenchymal stem cells， which are stem cells characterized by continuous self-renewal and differentiation. The key to strengthening bone remodeling is to improve the osteogenic differentiation capacity， which is the key point to inhibit bone resorption and prevent bone marrow mesenchymal stem cells from differentiating into osteoclasts. Traditional Chinese medicine （TCM） has been used in the treatment of osteonecrosis in ancient times. It is recorded in the Treasury of Words on Materia Medica （《本草汇编》） that "The deficiency in the lower energizer cannot be tonified without Eucommiae Cortexz.The soreness in lower legs cannot be alleviated without Eucommiae Cortex...The pain in the waist and knee cannot be relieved without Eucommiae Cortex...Tonifying liver and invigorating kidney， Eucommiae Cortex is an essential medicine." This indicates that ancient physicians have already begun to use the liver-tonifying， kidney-invigorating， and sinew-bone-strengthening effects of Eucommiae Cortex for the treatment of osteonecrosis. As the national support for the development of TCM strengthens， increasing studies have been conducted on the TCM prevention and treatment of steroid-induced osteonecrosis of femur head. Studies have suggested that Chinese medicinal herbs can exert a positive effect on the differentiation of bone marrow mesenchymal stem cells by affecting targeted signaling molecules， and promote osteogenesis and bone defect repair， thus combating the occurrence and development of steroid-induced osteonecrosis of femur head. The regulation of osteogenic signaling pathway by Chinese medicines to prevent steroid-induced osteonecrosis of femoral head has become a hot research topic. This article reviews the studies about the prevention and treatment of steroid-induced osteonecrosis of femur head with the active components in Chinese medicinal herbs by regulating osteogenic signaling pathways. We then explore the mechanism of the active components in promoting the differentiation of bone marrow mesenchymal stem cells into osteoblasts and inhibiting their differentiation into osteoclasts to facilitate bone formation， aiming to provide a reference for the further study of treating steroid-induced osteonecrosis of femoral head with Chinese medicinal herbs.

Traditional Chinese Medicine in Prevention and Treatment of Osteonecrosis of Femoral Head Based on OPG/RANK/RANKL Signaling Pathway： A Review / 中国实验方剂学杂志

Osteonecrosis of the femoral head （ONFH） is a painful and debilitating disease caused by impaired blood supply to the femoral head and cellular and tissue degeneration， leading to gradual destruction of the bone structure and progressive collapse of the femoral head. The main pathological mechanism of ONFH is the disruption of the balance between bone absorption and the reconstruction of new bone， resulting from microcirculation damage and decreased cellular tissue ability. This imbalance leads to biomechanical changes and accelerates the pathological progression of ONFH. In the early stages， clinical manifestations may not be obvious， mainly presenting as pain or discomfort in the hip or groin area， which can be relieved after rest. In the later stage of the disease， pain intensifies， and limb shortening， lower limb weakness， difficulty walking， or limping may occur. Currently， western medicine commonly uses osteogenic agents， anticoagulants， and artificial joint replacement for treatment， but there are also many issues such as prosthesis loosening and infection. Research has shown that traditional Chinese medicine （TCM） treatment of ONFH takes a holistic approach and employs multi-functional， multi-target， and multi-system Chinese medicine therapies， ensuring the safety and effectiveness of the treatment. The osteoprotegerin （OPG）/receptor activator of nuclear factor-κB （RANK）/RANK ligand （RANKL） signaling pathway plays a crucial role in maintaining the dynamic balance of bone remodeling. TCM treatments utilize this pathway to promote apoptosis of osteoclasts， reduce bone resorption， and accelerate bone formation， thereby playing an important role in the prevention and treatment of ONFH. This paper reviewed the role of OPG/RANK/RANKL signaling pathway and related cytokine expression in ONFH by reviewing relevant literature in China and abroad and research status of Chinese medicinal monomers， Chinese medicinal formulations， and combinations with physical therapy in increasing osteoblast secretion， promoting OPG expression， enhancing cytokine expression levels， and inhibiting osteoclast activity for the prevention and treatment of ONFH. This paper is expected to provide new ideas and directions for TCM in the prevention and treatment of ONFH.

Robot-assisted core decompression combined with bone grafting in the treatment of early osteonecrosis of femoral head / 中华骨科杂志

Objective:To explore the clinical effect of robot-assisted core decompression combined with bone grafting in the treatment of early-stage osteonecrosis of femoral head.Methods:The data of 49 patients (84 hips) who attended the Department of Orthopedics and Joint Surgery of the Second Affiliated Hospital of Xi'an Jiaotong University from August 2019 to February 2021 were retrospectively analyzed. All the patients suffering Association Research Circulation Osseous (ARCO) II stage of osteonecrosis of femoral head underwent core decompression and bone grafting. Among the patients undergoing surgery, 30 patients (54 hips), including 19 males and 11 females, aged 44.3±5.4 years (range, 21 to 59 years) were treated with conventional surgical methods, and 19 patients (30 hips), including 12 males and 7 females, aged 41.4±7.2 years (range, 20 to 58 years), were assisted by the orthopedic robot navigation system. All operations were performed by the same operator. All patients were informed of the conventional and robotic surgical options by the surgeon at admission, and the patients made the decision. The baseline data of the two groups of patients, the time of unilateral operation, the number of unilateral X-ray fluoroscopy, the Harris hip score at the last follow-up after surgery, the visual analog score (VAS), and the collapse rate at the last follow-up were collected and compared.Results:A total of 41 patients (70 hips) were followed up, including 24 cases (42 hips) in the conventional surgery group and 17 cases in the robot-assisted group (28 hips). The average follow-up time of all cases was 14.6±4.8 months (range, 3 to 21 months). At the last follow-up, a total of 13 patients (13 hips) suffered femoral head surface collapse, including 11 patients in the conventional surgery group (11 hips) and 2 patients in the robot-assisted group (2 hips). The rate of femoral head collapse between the two groups had statistical difference ( P=0.045). The average operation time of unilateral hip in the conventional operation group was 21.3±5.4 min, and 16.8±3.3 min in the robot-assisted group, with significant difference ( t=3.94, P<0.001). The number of X-ray fluoroscopy of unilateral hip in the conventional operation group was 14.4±3.8 times, and 9.6±2.1 times in the robot-assisted group, with significant difference ( t=6.08, P<0.001). The Harris hip score before surgery in the conventional surgery group was 68.4±4.5 points, and 85.1±3.8 points at the last follow-up, while the preoperative Harris hip score of the robot-assisted surgery group was 67.2±3.9 points, and 86.5±4.4 points at the last follow-up. The Harris hip scores at the last follow-up of the two groups were significantly different from those before the operation, but there was no difference between the two groups after surgery ( t=1.09, P=0.283). The preoperative VAS of the conventional surgery group was 4.8±1.7 points, and 1.7±0.8 points at the last follow-up. The preoperative VAS of the robot-assisted surgery group was 5.1±1.5 points, and 0.9±0.3 points at the last follow-up. Τhere were significant differences between the two groups regarding the VAS in the last follow-up ( t=3.92, P<0.001). Conclusion:Core decompression combined with bone grafting have a definite effect in the treatment of osteonecrosis of ARCO II stage of osteonecrosis of femoral head. Compared with conventional surgery, robot-assisted surgery can achieve better short-term results and head preservation rate.

Osteoclast-mediated pain and collapse mechanisms in the femoral head necrosis with bone marrow edema / 西安交通大学学报(医学版)

【Objective】 To explore pain and collapse mechanisms in fosteonecrosis of the femoral head (ONFH) with bone marrow edema (BME). 【Methods】 ONFH patients at ARCO Ⅲ stage who underwent total hip arthroplasty in the First Affiliated Hospital of Guangzhou University of Chinese Medicine were enrolled; the femoral head samples, clinical and imaging data were collected. These patients were divided into BME group and non-BME group according to the MR data in one week preoperative. Hematoxylin-eosin and Sirius red staining were performed to observe the morphological changes in bone tissue of femoral head specimens. Western blotting and qPCR were used to semi-quantitatively analyze the expression levels of CTSK, RANKL, and Netrin-1 proteins and mRNA in different regions of the bone tissue. 【Results】 Clinical and imaging data showed that ONFH patients with BME had significantly higher scores of VAS than ONFH patients without BME. Hematoxylin-eosin staining showed that bone structure disorder and a large number of empty bone lacunae were found in the necrotic areas in both groups, but there exited significant granulation tissue in the BME group, and spindle-shaped fibroblastic cells and inflammatory cells aggregated in the repaired region. Sirius red staining revealed the necrotic and sclerotic areas were accumulated with many collagenous fiber in the BME group. The results of Western blotting and qPCR showed that Netrin-1 expressions in the necrotic, sclerotic and health areas in the BME group were higher than those in the non-BME group (P<0.05), while osteoclast related proteins and mRNA expressions of the necrotic and sclerotic areas in the BME group was higher than those in the non-BME group (P<0.05). 【Conclusion】 All these findings indicated that hip pain was positively correlated with femoral head necrosis with BME, hyperactive osteoclasts participated in the femoral head collapse with BME, and the upregulated expression of Netrin-1 mediated the pain mechanism.

Exploring the intervention mechanism of Ginkgo biloba for steroid-induced necrosis of the femoral head based on network pharmacology / 中国临床药理学与治疗学

AIM: To explore the mechanism of Ginkgo biloba in the treatment of steroid-induced osteonecrosis of the femoral head based on network pharmacology. METHODS: The active ingredients and targets of Ginkgo biloba were predicted by the TCMSP, ADME, and PharmMapper databases. The disease targets related to steroid-induced osteonecrosis of the femoral head were searched by the GeneCards and OMIM databases. Cytoscape 3.6.1 was used to construct a protein-protein interaction network. The core target analysis, modular analysis, GO enrichment analysis, and KEGG pathway analysis of the targets of Ginkgo biloba in the intervention of steroid-induced osteonecrosis of the femoral head were performed by the STRING database. RESULTS: In this study, a total of 16 active ingredients of Ginkgo biloba and 547 targets were screened, of which 133 targets were related to steroid-induced femoral head necrosis. By PPI network topology analysis, TP53, AKT1, IL6, VEGFA, MAPK1, JUN, MAPK8, EGFR, EGF, and MYC were identified as the core targets. GO modularization analysis showed that these core targets were mainly related to apoptosis and angiogenesis. GO enrichment analysis was used to analyze the biological processes, cellular localization, and molecular functions of the core targets. KEGG enrichment analysis showed that the targets were mainly involved in molecular signaling pathways, among which the PI3K/AKT signaling pathway was the most relevant. CONCLUSION: Ginkgo biloba can inhibit steroid-induced osteonecrosis of the femoral head through multiple components, targets, and pathways, which provides the theoretical basis and reference for subsequent cell and animal experiments.

Analysis of influence of MR signs on Harris score in ARCO stages 2-4 femoral head necrosis / 中国骨伤

OBJECTIVE@#To analysis and determine MR signs of Harris score ARCO stages 2-4 in osteonecrosis of femoral head (ONFH).@*METHODS@#Thirty-four patients with ONFH of ARCO stages 2 to 4 who underwent routine MR, T2 mapping, 3D-SPACE sequence examination and Harris score were retrospectively collected from January 2019 to June 2020, and 3 patients were excluded, and 31 patients were finally included, including 23 males and 8 females, aged from 18 to 62 years old with an average of(40.0±10.8) years old. Among them 21 patients with bilateral femoral head necrosis, totally 52 cases, including 17 with ARCO stage 2 patients, 24 ARCO stage 3, and 11 ARCO stage 4. MR imaging signs (femoral head collapse depth, ONFH index, bone marrow edema, hyperplasia, grade and T2 value of cartilage injury, and joint effusion) were scored and measured on the picture archiving and communication system (PACS) workstation, and the cartilage quantitative parameter T2 value was calculated and measured on Siemens postprocessing workstation. Pearson correlation analysis was used to evaluate the correlation between various MR signs and Harris score, and then multiple linear regression analysis was used to examine impact of MR signs on Harris hip score.@*RESULTS@#Femoral head collapse depth(r=-0.563, P=0.000), grade of cartilage injury(r=-0.500, P=0.000), and joint effusion (r=-0.535, P=0.000) were negatively correlated with Harris score by Pearson correlation analysis. Multiple linear regression analysis showed that joint effusion(β=-6.198, P=0.001) and femoral head collapse depth(β=-4.085, P=0.014) had a significant negative impact on Harris hip score.@*CONCLUSION@#Femoral head collapse depth and joint effusion both had significant negative relationship with Harris hip score. It is recommended to routinely evaluate femoral head collapse depth and joint effusion quantitatively and gradedly, so as to efficiently and accurately assist clinical diagnosis and treatment.

Clinical application study of multiple small-diameter drilling combined with extracorporeal shock wave therapy (ESWT) under C-arm positioning in the treatment of early femoral head necrosis / 中国骨伤

OBJECTIVE@#To explore the therapeutic effect of multiple small diameter drilling combined with extracorporeal shock wave therapy (ESWT) under C-arm X-raylocalization in patients with early osteonecrosis of the femoral head (ONFH).@*METHODS@#A total of 106 cases of early ONFH patients admitted from May 2015 to May 2017 were retrospectively selected as the study subjects. According to different treatment methods, the patients were divided into observation group and control group, 53 cases in each group. The observation group was treated with multiple small-diameter drilling combined with ESWT under C-arm positioning in the observation group, including 41 males and 12 females with an age of (45.85±6.01) years old (22 to 70 years old);and the control group was treated with ESWT, including 34 males and 19 females with an age of (45.12±5.83) years old(20 to 68 years old) in the control group. The modified Harris hip scores(mHHS), visual analog scale(VAS), hip flexion range, hip abduction and adduction range, ONFH area ratio and clinical efficacy were compared between twe groups before and after treatment. Kaplan-Meier method was used to draw a survival curve to compare the femoral head survival rate between two groups during the 3-year follow-up period after treatment.@*RESULTS@#There were no complications such as poor wound healing and infection. All of 106 patients were followed up for 28 to 36 months with an average of (31.06±4.28) months. MHHS score, hip flexion range and hip abduction and adduction range in the observation group were increased from (63.85±5.42) scores, (23.79±2.21) °, (32.40±4.19) ° before treatment to (85.51±5.69) scores, (34.65±2.73)°, (43.32±5.71)° at 2 years after treatment, respectively(P<0.05). The above indicators in the control group increased from (64.73±5.64)°, (23.82±2.18)°, (32.45±4.13)° before treatment to (81.65±5.48) scores, (32.79±2.87)°, (39.75±5.68)°at two years after treatment, respectively(P<0.05). VAS score and ONFH area ratio in the observation group decreased from (5.76±1.41) scores and (35.07±4.96)% before treatment to (3.39±1.02) scores and (22.04±3.23)% at 2 years after treatment, respectively(P<0.05). The above indicatiors in control group decreased from (5.73±1.45) scores and (35.24±5.18)% before treatment to (4.43±1.21) scores and (28.32±3.76)% at 2 years after treatment, respectively(P<0.05), and the improvement in the observation group was significantly higher than that in the control group(P<0.05). At 3 years after treatment, the femoral head survival rate in the observation group was higher than that in the control group (P<0.05).@*CONCLUSION@#Multiple small diameter drilling combined with ESWT under C-arm positioning can significantly improve the clinical symptoms of patients with early ONFH, relieve pain and improve clinical efficacy.

Expert consensus on clinical drug prevention and treatment of osteonecrosis of the femoral head(2022) / 中国骨伤

With the in-depth understanding of osteonecrosis of femoral head (ONFH), and more and more patients seeking medical treatment in the early stage of the disease, surgical treatment of femoral head necrosis alone is no longer sufficient for the current treatment of patients' demand, how to rationally and effectively apply drugs to strengthen the early prevention and treatment of femoral head necrosis and delay the progression of disease is becoming more and more important. This article combines the latest expert consensus and evidence-based medical evidence on the principles of ONFH diagnosis and treatment in Chinese and Western medicine at home and abroad, combined with domestic actual clinical application experience, and is organized by experts from Association Related to Circulation Osseous Chinese Microcirculation Society (CSM-ARCO) to write this consensus, focusing on the types of ONFH drugs, the characteristics, safety, rationality and basic principles of drug use provide reference opinions for the safe, reasonable, standardized and effective drug use of medical institutions at all levels. This consensus is only an expert guideline based on literature and clinical experience, not as a requirement for mandatory implementation, let alone as a legal basis. The clinical practice could be tailored to the actual local conditions to develop appropriate prevention and treatment measures for patients.