Anatomical Diversity in Femur bones: Understanding the Morphological Variability for Surgical and Prosthetic Applications / Diversidad Anatómica en Huesos Fémur: Comprensión de la Variabilidad Morfológica para Aplicaciones Quirúrgicas y Protésicas

SUMMARY: The femur, the body's longest bone, plays a critical role in orthopaedics and radiology. Understanding its anatomy, particularly the neck-shaft angle (NSA), is vital for diagnosing bone issues and designing hip implants. While some Asian populations' femur measurements have been studied, there is a research gap concerning Sri Lankans. This study aimed to fill this gap by examining the proximal femur's anatomy in the Sri Lankan population. We analysed 45 adult human femurs (26 right, 19 left) of unknown sex, ethically sourced from the University of Sri Jayewardenepura. Femurs with fractures or pathologies were excluded. Precise measurements were recorded using digital vernier callipers, with millimetre accuracy. Parameters included mean femoral length, vertical and transverse femoral head diameters, neck axis and neck length. Each measurement was taken three times to minimize subjectivity. Right femurs had a mean length of 42.8 mm (SD±2.64), while left femurs measured 43.53 mm (SD±3.27). Mean NSA was 125.78º (SD±4.45) for left femurs and 127.59º (SD±2.06) for right. Mean femoral head diameters were 4.09mm (SD±0.30) (right) and 4.12mm (SD±0.31) (left). Mean anterior neck lengths of the right and left were 2.61 (SD±0.54) and 2.71(SD±0.50) respectively. Comparing our findings with other Asian populations highlighted significant variations in femur measurements. These discrepancies emphasize the need for population-specific data for orthopaedic interventions and raise questions about the suitability of imported prosthetics. Differences in femur length, neck length, and NSA between sides suggest potential challenges in using implants designed for one side on the other. This study underscores the necessity of population-specific data in orthopaedics, as femur measurements differ even among Asian populations. Further research and statistical analysis are essential for tailoring orthopaedic solutions to individual populations. The findings also suggest a potential need for locally manufactured prosthetics to better suit the Sri Lankan population.

El fémur, el hueso más largo del cuerpo, desempeña un papel fundamental en ortopedia y radiología. Comprender su anatomía, en particular el ángulo cuello-diáfisis (NSA), es vital para diagnosticar problemas óseos y diseñar implantes de cadera. Si bien se han estudiado las medidas del fémur de algunas poblaciones asiáticas, existe un vacío en la investigación sobre los habitantes de Sri Lanka. Este estudio tuvo como objetivo examinar la anatomía del fémur proximal en la población de Sri Lanka. Analizamos 45 fémures humanos adultos (26 derechos, 19 izquierdos) de sexo desconocido, obtenidos éticamente de la Universidad de Sri Jayewardenepura. Se excluyeron fémures con fracturas o patologías. Se registraron mediciones precisas utilizando calibradores vernier digitales, con precisión milimétrica. Los parámetros incluyeron la longitud femoral media, los diámetros vertical y transversal de la cabeza femoral, el eje del cuello y la longitud del cuello. Cada medición se tomó tres veces para minimizar la subjetividad. Los fémures derechos tuvieron una longitud media de 42,8 mm (DE ± 2,64), mientras que los fémures izquierdos midieron 43,53 mm (DE ± 3,27). La NSA media fue de 125,78º (DE±4,45) para el fémur izquierdo y de 127,59º (DE±2,06) para el derecho. Los diámetros medios de la cabeza femoral fueron 4,09 mm (DE ± 0,30) (derecha) y 4,12 mm (DE ± 0,31) (izquierda). Las longitudes medias del cuello anterior de la derecha y la izquierda fueron 2,61 (DE ± 0,54) y 2,71 (DE ± 0,50) respectivamente. La comparación de nuestros hallazgos con otras poblaciones asiáticas destacó variaciones significativas en las medidas del fémur. Estas discrepancias enfatizan la necesidad de datos específicos de la población para las intervenciones ortopédicas y plantean dudas sobre la idoneidad de las prótesis importadas. Las diferencias en la longitud del fémur, la longitud del cuello y la NSA entre lados sugieren posibles desafíos al utilizar implantes diseñados para un lado en el otro. Este estudio subraya la necesidad de datos específicos de la población en ortopedia, ya que las mediciones del fémur difieren incluso entre las poblaciones asiáticas. Es esencial realizar más investigaciones y análisis estadísticos para adaptar las soluciones ortopédicas a poblaciones individuales. Los hallazgos también sugieren una posible necesidad de prótesis fabricadas localmente para adaptarse mejor a la población de Sri Lanka.

Animal Model Standardization for Studying Avascular Necrosis of the Femoral Head in Legg-Calvé-Perthes Disease / Padronização de modelo animal para o estudo da necrose isquêmica da cabeça femoral na doença de Legg-Calvé-Perthes

Abstract Objective Testing an experimental model for ischemic necrosis of the femoral head in Legg-Calvé-Perthes disease by evaluating gait, imaging and morphohistology. Methods The operation was done in 11 piglets. Necrosis by cerclage in the right femoral neck was induced. Piglets were divided into group A, with 8 animals, euthanizing two in the 2nd, 4th, 6th, and 8th weeks, respectively; and group B, with 2 animals (sham), submitted to the surgical procedure without cerclage of the right femoral neck. The gait classification used was that of Etterlin. The frozen femurs were submitted to digital radiography and computed tomography. The height and width of the epiphysis and epiphysary coefficient were measured at study times. Light microscopy and immunohistochemistry with TGF-β1 were performed. Results One animal died of sepsis in Group A. In this group, claudication was observed in all animals. On digital radiography and computed tomography, bone sclerosis, enlargement of the right femoral neck, flattening, collapse, and fragmentation of the right femoral head were observed. All epiphysis height and epiphysary coefficient values of the right femoral head were lower than the contralateral ones, in which were observed chondrocytes disordered and separated by gaps. A reduction in TGF-β1 expression was observed at 2 and 6 weeks in the right femoral head and at eight in the left. In group B, there were no signs of necrosis and gait was normal. Conclusions The model presented reproduced macroscopic necrosis on digital radiography, computed tomography, and microscopy. Gait evaluation showed a good correlation with other ischemia findings. Level of EvidenceV. Diagnostic studies.

Resumo Objetivo Testar um modelo experimental para necrose isquêmica da cabeça femoral na doença de Legg-Calvé-Perthes avaliando a marcha, exames de imagens e morfohistologia. Métodos Operaram-se 11 leitões. Induziu-se a necrose por cerclagem no colo femoral direito. Dividiram-se os leitões em grupo A com 8 animais, sacrificando-se dois na 2ª, 4ª, 6ª e 8ª semanas, respectivamente; e grupo B, com 2 animais (sham), submetidos ao procedimento cirúrgico sem a cerclagem do colo femoral direito. A classificação da marcha utilizada foi a de Etterlin. Os fêmures congelados foram submetidos à radiografia digital e tomografia computadorizada. Mediram-se a altura e largura da epífise e o coeficiente epifisário nos tempos de estudo. Realizou-se, microscopia de luz e imunohistoquímica com TGF-β1. Resultados Um animal morreu por sepse no grupo A. Neste grupo, observou-se claudicação em todos os animais. Na radiografia digital e tomografia computadorizada observaram-se: esclerose óssea, alargamento do colo femoral direito, achatamento, colapso e fragmentação da cabeça femoral direita. Todos os valores da altura da epífise e coeficiente epifisário da cabeça femoral direita foram menores que os contralaterais, nos quais observaram-se condrócitos desordenados e separados por lacunas. Observou-se redução da expressão do TGF-β1 com 2 e 6 semanas nas cabeças femorais direitas e nas esquerdas com oito. No grupo B, não ocorreram sinais de necrose e a marcha foi normal. Conclusões O modelo apresentado reproduziu a necrose macroscopicamente, na radiografia digital, tomografia computadorizada e microscopia. A avaliação da marcha demonstrou boa correlação com os demais achados de isquemia. Nível de EvidênciaV. Estudos diagnósticos.

Tratamiento ortésico de luxación de cadera derivada de osteomielitis del cuello del fémur. Presentación de dos casos

La osteomielitis es una inflamación ósea causada principalmente por bacterias. En los casos de osteomielitis del cuello del fémur y artritis séptica concomitante, las complicaciones pueden ocasionar, a largo plazo, acortamiento y deterioro articular considerables. Se describen los casos de dos pacientes neonatos, con manifestaciones de hipertermia como signo común; y solo en uno de ellos limitación del movimiento del miembro inferior derecho, contractura en flexión y aducción, dolorosa a la movilización. El diagnóstico se basó en criterios clínicos, imagenológicos y de laboratorio. El tratamiento consistió en el uso de la férula en abducción, lo cual garantizó la reducción concéntrica de la cabeza del fémur en la cavidad acetabular; esto pudo constatarse mediante seguimiento y control de la reducción, a través de radiografía simple de la pelvis en cada consulta. El diagnóstico precoz de la enfermedad determina el empleo de un tratamiento más conservador, además de minimizar la aparición de complicaciones.

Osteomyelitis is a bone inflammation caused mainly by bacteria. In cases of the femur's neck osteomyelitis and concomitant septic arthritis, complications can lead to considerable joint shortening and deterioration in the long term. The cases of two neonatal patients are described, with hyperthermia manifestations as a common sign; and only in one of them limited movement of the right lower limb, flexion and adduction contracture, painful on movement. The diagnosis was based on clinical, imaging and laboratory criteria. The treatment consisted in the use of the abduction splint, which guaranteed the concentric reduction of the femoral head in the acetabular cavity; this could be verified by monitoring and control of the reduction, through simple radiography of the pelvis in each consultation. The early diagnosis of the disease determines the use of a more conservative treatment, in addition to minimizing complications.

Biomechanical Gait Analysis in Patients with Osteonecrosis of the Femoral Head / Análise biomecánica da marcha de pacientes com osteonecrose da cabeça do fémur

Abstract Objectives Although osteonecrosis of the femoral head is a prevalent condition, its effects on gait parameters have not been thoroughly studied and are not well-established in the current literature. The primary aim of the present study is to describe gait in patients with a diagnosis of osteonecrosis. Methods This is a cross-sectional study. Nine patients diagnosed with osteonecrosis of the femoral head who were regularly followed-up at an outpatient clinic were selected for the present study and underwent gait analysis using Vicon Motion Capture Systems. Spatiotemporal data was obtained, and joint angles were calculated using an Euler angle coordinate system. Distal coordinate systems were used to calculate joint momentsand forceplatestoobtaingroundreactionforces. Results Patients with osteonecrosis presented with slower velocity (0.54 m/s ± 0.19) and smaller cadence (83.01 steps/min ± 13.23) than healthy patients. The pelvic obliquity range of motion was of 10.12° ± 3.03 and rotation was of 18.23° ± 9.17. The mean hip flexion was of 9.48° ± 3.40. Ground reaction forces showed reduced braking and propelling forces. Joint moments were reduced for flexion and adduction (0.42 Nm/kg ± 0.2 and 0.30 Nm/kg ± 0.11, respectively) but the abduction moment was increased (0.42 Nm/kg ± 0.18). Conclusions The present study showed that osteonecrosis of the femoral head presents compensatory gait mechanisms, with increased pelvic motion and decreased knee flexion to protect the hip joint. Decreased moments for hip flexion and adduction were also identified and muscle weakness for those groups may be correlated to the disease.

Resumo Objetivos Embora a osteonecrose da cabeça do fêmur seja uma lesão prevalente, seus efeitos sobre os parâmetros da marcha não foram minuciosamente estudados e não estão bem estabelecidos na literatura atual. O objetivo principal do presente estudo é descrever a marcha em pacientes com osteonecrose. Métodos Trata-se de um estudo transversal. Nove pacientes com diagnóstico de osteonecrose da cabeça do fêmur, sob acompanhamento regular em ambulatório, foram selecionados para o presente estudo e submetidos à análise da marcha com Vicon Motion Capture Systems. Os dados espaciais e temporais foram obtidos e os ângulos articulares foram calculados com o sistema de coordenadas angulares de Euler. Sistemas de coordenadas distais e plataformas de força foram utilizados para o cálculo de momentos articulares e de forças de reação ao solo, respectivamente. Resultados Os pacientes com osteonecrose apresentaram menor velocidade (0,54 m/s ± 0,19) e menor cadência (83,01 passos/minuto ± 13,23) do que pacientes saudáveis. As amplitudes de movimento de obliquidade e rotação pélvica foram de 10,12°± 3,03 e 18,23° ± 9,17, respectivamente. A média de flexão do quadril foi de 9,48° ± 3,40. O estudo das forças de reação ao solo revelou redução das forças de frenagem e propulsão. Os momentos articulares de flexão e adução caíram (0,42 Nm/kg ± 0,2 e 0,30 Nm/kg ± 0,11), mas o momento de abdução aumentou (0,42 Nm/kg ± 0,18). Conclusões O presente estudo mostrou que a osteonecrose da cabeça do fêmur é associada a mecanismos compensatórios da marcha, com aumento da movimentação pélvica e diminuição da flexão do joelho para proteção da articulação do quadril. A redução dos momentos de flexão e adução do quadril também foi identificada e a fraqueza destes grupos musculares pode estar correlacionada à doença.

Traditional Chinese Medicine Regulates Wnt/β-catenin Signaling Pathway to Treat Steroid-induced Femoral Head Necrosis： A Review / 中国实验方剂学杂志

Steroid-induced necrosis of the femoral head （SNOFH） is a common orthopedic disease，which is difficult to cure and has poor clinical prognosis. The number of SNOFH patients in China is still increasing year by year，which seriously threatens human health. Long-term non-standard or short-term extensive use of hormone （GC） is an important reason for the occurrence of this disease. At present，SNOFH is mostly treated by surgical methods such as hip replacement，which has limitations of great harm to patients and high cost. In recent years，with the continuous deepening and innovation of traditional Chinese medicine（TCM） research，the use of TCM to treat SNOFH has been widely used in clinical practice. The main TCM pathogenesis of SNOFH is kidney deficiency and blood stasis. Therefore，TCM monomer and compound compound of tonifying kidney and promoting blood circulation are used to treat SNOFH. And TCM has obvious therapeutic effect，small side effects，less cost and other advantages. Glycoprotein/beta chain protein secretion （Wnt/beta- catenin） signaling pathway as a classic signaling pathway is closely related to the bone，between its by promoting bone marrow mesenchymal stem cell update，enhance the activity of osteoblast and suppress the apoptosis，which adjust the metabolic balance of bone tissue，increase bone density，will play an important role in the process of bone formation. In recent years，the use of TCM monomers and compounds to regulate Wnt/β-catenin signaling pathway to accelerate bone marrow mesenchymal stem cells，promote their transformation into osteoblasts，and maintain bone metabolic balance mechanism to treat SNOFH has become a new research hotspot. This article reviews the research progress of TCM in the prevention and treatment of SNOFH by regulating Wnt/β-catenin signaling pathway，in order to provide reference for the application of TCM in the treatment of SNOFH.

Epiphysiolysis in a 22-year-old Patient with Congenital Hypogonadotropic Hypogonadism: Case Report / Epifisiólise em paciente de 22 anos de idade com hipogonadismo hipogonadotrópico congênito: Relato de caso

Abstract Epiphysiolysis is a relatively common disease in the adolescent population (9-16 years); however, it is rare in the adult population. It is characterized by non-traumatic proximal femur slipping. When it occurs in this population it is associated with some disease that slows sexual development and physis closure, such as endocrine diseases or brain tumors. The aim of the present study is to report a case of epiphysiolysis in a 22-year-old patient with hypogonadotropic hypogonadism. There are only 63 cases reported in the world literature on epiphysiolysis in the adult population.

Resumo A epifisiólise é uma doença relativamente comum na população adolescente (de 9-16 anos), entretanto rara na população adulta. Se caracteriza pelo escorregamento metáfiso-epifisário do fêmur proximal não-traumático. Quando ocorre nessa população, está associada a alguma doença que retarda o desenvolvimento sexual e fechamento fisário, como doenças endocrinológicas ou tumores cerebrais. O objetivo do presente estudo é relatar um caso de epifisiólise numa paciente com 22 anos de idade e hipogonadismo hipogonadotrófico. Existem apenas 63 casos relatados na literatura mundial sobre epifisiólise na população adulta.

Orthotopic osteochondral transplantation for the treatment of femoral head compression fracture: a case report and literature review / 中华骨科杂志

Femoral head fracture is commonly seen in high-energy injury. However, compression fracture of femoral head is more rare. In most classifications of femoral head fracture, the compression is unusually involved. A case about acute traumatic dislocation of hip joint with compression fracture of femoral head is reported, involving a patient who hurt himself by riding electric bike and hitting the flower bed. He came to our hospital complaining of pain and limited motion of his right leg. The diagnosis of right hip anterior dislocation with the compression fracture of femoral head was confirmed by medical history, physical examination and imaging. Closed reduction of hip dislocation was performed in an emergency. Then we transplanted the bone cartilage from the non-weight-bearing area under the femoral head to the collapsed weight-bearing area, fixing it with countersunk hollow screws, and then the non-weight-bearing donor area was reconstructed with autogenous iliac bone, using surgical hip dislocation. The anatomical structure of the femoral head was therefore restored successfully during the operation. Three months after surgery, the X-ray showed that the femoral head was smooth and the cartilage graft was well fixed. Eight months after surgery, the patient gradually increased the bearing weight from partial to full according to his own condition, and there was no obvious pain in hip. After 24-month follow-up, we found the X-rays showed good reduction and fixation of the femoral head fracture. The CT scan showed no necrosis or cystic degeneration. He got well-active and passive movement in hip joint, and got no pain when walking with burden. For the patient with hip dislocation and compression fracture of femoral head, early joint reduction and non-weight-bearing osteocartilage transplantation can restore the anatomical structure of the weight-bearing area of the femoral head, to avoid traumatic osteoarthritis, and to improve the long-term quality of life of patients.

A deep transfer learning method using plain radiographs for the differential diagnosis of osteonecrosis of the femoral head with other hip diseases / 中华骨科杂志

Objective:To develop a deep transfer learning method for the differential diagnosis of osteonecrosis of the femoral head (ONFH) with other common hip diseases using anteroposterior hip radiographs.Methods:Patients suffering from ONFH, DDH, and other hip diseases including primary hip osteoarthritis, non-infectious inflammatory hip disease, and femoral neck fracture treated in the First Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2018 to December 2020 were enrolled in the study. A clinical data set containing anteroposterior hip radiographs of the eligible patients was created. Data augmentation by rotating and flipping images was performed to enlarge the data set, then the data set was divided equally into a training data set and a testing data set. The ResNet-152, a deep neural network model, was used in the study, but the original Batch Normalization was replaced with Transferable Normalization to construct a novel deep transfer learning model. The model was trained to distinguish ONFH and DDH from other common hip diseases using anteroposterior hip radiographs on the training data set and its classification performance was evaluated on the testing data set.Results:The clinical data set was comprised of anteroposterior hip radiographs of 1024 hips, including 542 with ONFH, 296 with DDH, and 186 with other common hip diseases (56 hips with primary osteoarthritis, 85 hips with non-infectious inflammatory osteoarthritis, 45 hips with femoral neck fracture). After data augmentation, the size of the data set multiplied to 6144. The model was trained 100 050 times in each task. Accuracy was used as the representative parameter to evaluate the performance of the model. In the binary classification task to identify ONFH, the best accuracy was 95.80%. As for the multi-classification task for classification of ONFH and DDH from other hip diseases, the best accuracy was 91.40%. The plateau of the model was observed in each task after 50 000 times of training. The mean accuracy in plateaus was 95.35% (95% CI: 95.33%, 95.37%), and 90.85% (95% CI: 90.82%, 90.87%), respectively. Conclusion:The present study proves the encouraging performance of a deep transfer learning method for the first-visit classification of ONFH, DDH, and other hip diseases using the convenient and economical anteroposterior hip radiographs.

Early efficacy of rotational femoral neck osteotomy with preservation of the round ligament in treating subchondral insufficiency fracture of the femoral head in young and middle-aged population / 中华创伤杂志

Objective:To investigate the short-term efficacy of rotational femoral neck osteotomy with preservation of the round ligament in the treatment of subchondral insufficiency fracture of the femoral head (SIFFH) in young and middle-aged people.Methods:A retrospective case series study was used to analyze the clinical data of 13 patients with SIFFH, who were admitted to 920th Hospital of Joint Logistics Support Force from January 2017 to January 2022. The patients included 10 males and 3 females, aged 22-49 years [(33.5±8.3)years]. There were 6 patients with fracture on the left hip and 7 on the right hip. All the patients were treated by rotational femoral neck osteotomy with preservation of the round ligament. Postoperatively, standardized joint functional training was given. The operative time and intraoperative bleeding were recorded. The modified Harris hip score and visual analogue score (VAS) were compared preoperatively, at 3, 6 months postoperatively and at the final follow-up. Radiological examinations were used to observe the occurrence of any collapse of the femoral head, non-union at osteotomy site or other complications.Results:The patients were followed up for 13-24 months [(17.9±3.1)months]. The operative time was (127.3±9.8)minutes, with the intraoperative bleeding of (393.9±21.9)ml. The values of modified Harris hip score were (61.6±3.3)points, (80.2±4.4)points, and (91.9±4.1)points at 3, 6 months postoperatively and at the final follow-up, respectively, being significantly higher than the preoperative (51.4±3.5)points (all P<0.05), and there were significant differences between different postoperative timepoints (all P<0.05). The values of VAS were (4.9±1.1)points, (3.0±0.9)points, and (1.4±0.5)points at 3, 6 months postoperatively and at the final follow-up, respectively, being significantly lower than preoperative (6.7±0.9)points (all P<0.05), and there were significant differences between different postoperative timepoints (all P<0.05). Imaging examination showed no femoral head collapse, with all the bones healed at the osteotomy site. There were no serious complications such as bone non-union, incision infection or peripheral nerve injury. Conclusion:Rotational femoral neck osteotomy with preservation of the round ligament in treating SIFFH in the young and middle-aged population has the advantages of shortened operative time, less intraoperative bleeding, promoted hip function recovery, attenuated pain and decreased complications, showing a satisfactory early effect.

Research progress in hip-preserving modalities for early osteonecrosis of the femoral head in young and middle-aged patients / 中华创伤杂志

Osteonecrosis of the femoral head (ONFH) is one of the common and difficult-to-treat orthopedic diseases caused by a variety of factors that lead to abnormal blood flow to the femoral head, which in turn leads to deformation and collapse of the femoral head and eventually results in severe hip joint dysfunction. The key to the treatment is early diagnosis and correct treatment according to the stage classification and active prevention of further aggravation of ONFH aiming to delay or avoid hip replacement surgery in young and middle-aged patients. At present, there are various non-surgical and surgical hip-preserving modalities for early ONFH, designed to slow down the progression of the disease, prevent the femoral head from collapsing and stop the mild collapse. In recent years, with the emergence and development of bone reconstruction biomaterials, artificial bone reconstruction after scraping of ONFH lesions has shown great potential in the treatment of early ONFH. The authors review the research progress in hip-preserving modalities for early ONFH in young and middle-aged patients from non-surgical and surgical perspectives, hoping to provide a reference for clinical treatment of early ONFH.

Avascular Necrosis After Modified Dunn Surgery for the Treatment of Slipped Capital Femoral Epiphysis* / Necrose avascular pós-cirurgia de Dunn modificada no tratamento do escorregamento da epífise proximal do fêmur*

Abstract Objective The present study analyzed the incidence of epiphyseal avascular necrosis in patients with slipped capital femoral epiphysis (SCFE) treated using a modified Dunn technique. In addition, this study determined the correlation of other variables with this incidence and described treatment complications. Methods This is a retrospective study with 20 patients treated by the same surgical team from 2009 to 2019 and followed up for 2 to 12 years. The analysis included general features, time from presentation to surgical procedure, classification, and intraoperative blood perfusion of the epiphysis, as well as complications and their treatment. Results All cases were severe; 65% were acute on chronic, and 55% of the SCFEs were unstable. Our complication rate was 45%, with 5 cases of avascular necrosis, 2 cases of deep infection, 1 case of material failure, and 1 case of joint instability. The statistical analysis revealed that the risk of necrosis was higher when the surgery occurred after a long hospitalization time and there was no intraoperative epiphyseal perfusion. Four necrosis cases happened within the first 5 years, and 1 case in the last 5 years of the study. Conclusion Our study showed that necrosis was the most common complication. It also revealed that surgery delay and lack of intraoperative epiphysis perfusion potentially predispose to avascular necrosis. Although with no statistical significance, coxofemoral instability occurred in chronic SCFE, and surgical fixation with threaded wires was less effective than fixation with a cannulated screw. The modified Dunn procedure should be reserved for severe cases in which other techniques are not feasible and performed by an experienced, trained, and qualified team.

Resumo Objetivo Analisar a incidência da necrose avascular da epífise no tratamento do escorregamento da epífise proximal do fêmur pela técnica de Dunn modificada, correlacionando-a com outras variáveis. Como objetivo secundário, descrevemos outras complicações encontradas. Métodos Estudo retrospectivo com 20 pacientes tratados entre 2009 e 2019, com seguimento de 2 a 12 anos, tratados pela mesma equipe cirúrgica. A análise incluiu características gerais, tempo entre apresentação e procedimento cirúrgico, classificação, presença de perfusão sanguínea intraoperatória da epífise, avaliação das complicações e seus respectivos tratamentos. Resultados Todos os casos eram graves, 65% crônicos agudizados e 55% dos escorregamentos eram instáveis. Nossa taxa de complicações foi de 45%, sendo 5 casos de necrose avascular, 2 de infecção profunda, uma falha do material e uma instabilidade articular. Pacientes operados com maior tempo após a internação e os sem perfusão intraoperatória da epífise tiveram maior risco de necrose na análise estatística. Considerando o tempo do estudo, tivemos 4 casos de necrose nos primeiros 5 anos e 1 caso nos últimos 5 anos. Conclusão Nosso estudo demonstrou que a necrose foi a complicação mais comum e que o atraso para a realização da cirurgia e a ausência de perfusão da epífise no intraoperatório podem predispor à necrose avascular. Embora não estatisticamente significante, a instabilidade coxofemoral foi observada na forma de apresentação crônica e a fixação cirúrgica com fios rosqueados se mostrou menos eficaz que a fixação com parafuso canulado. Este procedimento deve ser reservado para casos graves nos quais outras técnicas não sejam possíveis e realizado por equipe experiente, treinada e capacitada.

Osteonecrosis of the Femoral Head: Update Article / Osteonecrose da cabeça femoral: Artigo de atualização

Abstract Among the pathologies that affect the hip joint, osteonecrosis of the femoral head (ONFH) is probably the most intriguing and challenging. It consists of a multifactorial disease with a highly-variable spectrum in its clinical presentation. It has a devastating effect, due to disabling painful conditions, both for usual activities and sports. Given the huge range of risk factors, such as prolonged use of corticosteroids (especially in cases of rheumatologic diseases), trauma sequelae, sickle cell anemia, HIV, alcoholism, smoking, blood dyscrasias, and several other diseases that compromise the blood supply to the femoral head, ONFH has a varied clinical presentation and prognosis, which makes it difficult to determine a specific treatment, especially in cases in which chondral involvement has not yet occurred and the hip joint is still preserved. These are the main factors found in the literature that determine the classifications of this pathology. The range of treatments includes several options for cases in which an attempt is made to save the joint: conservative treatment, traditional decompression and/or combined with some type of adjuvant treatment (homologous grafting, synthetic grafting, vascularized grafts, tantalum screws, and bone marrow aspirate injection), and, for cases in which there is already a subchondral fracture and/or collapse of the femoral head and/or a reduction in the joint space, femoral osteotomies or total hip arthroplasty are commonly performed.

Resumo Entre as patologias que acometem a articulação coxofemoral, a osteonecrose da cabeça femoral (ONCF) é provavelmente a mais intrigante e desafiadora. Consiste em uma doença multifatorial, com um espectro muito variável em sua apresentação clínica. Tem efeito devastador, devido a quadros dolorosos incapacitantes tanto para atividades habituais quanto esportivas. Dada a gama enorme de fatores de risco, tais como uso prolongado de corticoides (principalmente em casos de doenças reumatológicas), sequelas de trauma, anemia falciforme, HIV, etilismo, tabagismo, discrasias sanguíneas, e várias outras doenças que comprometem a irrigação sanguínea da cabeça femoral, a ONCF tem apresentação clínica e prognósticos bem variados, o que dificulta a determinação de um tratamento específico, especialmente em casos nos quais ainda não houve acometimento condral e a articulação do quadril ainda se mantém preservada, sendo estes os principais fatores encontrados na literatura que determinam as classificações desta patologia. No leque de tratamentos, encontramos diversas opções para os casos em que setenta salvar a articulação: tratamento conservador, descompressão simples e/ou associada a algum tipo de tratamento adjuvante (enxertia homóloga, enxertia sintética, enxertos vascularizados, parafusos de tântalo, e injeção de aspirado de medula óssea), e, para casos nos quais já há fratura subcondral e/ou colapso da cabeça femoral e/ou diminuição do espaço articular, reserva-se, comumente, a realização de osteotomias femorais ou artroplastia total do quadril.

Protective effect of Yougui Yin on steroid-induced avascular necrosis of femoral head in rats by regulating the Wnt/β-catenin signaling pathway / 国际中医中药杂志

Objective:To investigate the effect of Yougui Yin on steroid-induced femoral head necrosis in rats and the regulation of Wnt/β-catenin signaling pathway, and to explore its mechanism.Methods:Fifty SD rats were randomly divided into normal group, model group, high-dose group (26.4 g/kg), medium-dose group (13.2 g/kg) and low-dose group (6.6 g/kg) of Yougui Yin, with 10 rats in each group. Except the normal group, the other groups were prepared with SANFH model by combining LPS and methylprednisolone injection. The treatment groups were intragastrically administered with Yougui Yin, once a day for 8 weeks. After the final administration, the serum calcium and phosphorus levels of rats in each group were determined by automatic biochemical analyzer. The femoral head specimens of rats in each group were detected by MRI, and the pathological changes of the femoral head were observed by HE staining. The expressions of caspase-3, β-catenin and Wnt3α mRNA in the femoral head of rats were detected by RT-PCR.Results:Compared with the model group, the levels of serum calcium and phosphorus in the medium and high dose groups were increased significantly ( P<0.05, P<0.01), and the level of serum phosphorus in the low dose group was increased significantly ( P<0.05); In the medium and high dose groups, the femoral empty bone lacuna rate was decreased ( P<0.05, P<0.01); The expression of caspase-3 mRNA (2.146±0.191, 1.688±0.247, 1.370±0.252 vs. 2.535±0.236) in the low, medium and high dose groups were decreased ( P<0.05, P<0.01), and the expression of β-catenin mRNA (0.433±0.102, 0.496±0.091, 0.698±0.089 vs. 0.259±0.106) were increased ( P<0.05, P<0.01); The expression of Wnt3α mRNA (0.509±0.061, 0.833±0.053 vs. 0.384±0.052) in the medium and high dose groups were increased ( P<0.05, P<0.01); In the medium and high dose groups, MRI showed higher T2 signals around the joint, and high T2 signals within the joint, which were clearly distinguished from the femoral head cartilage, and there was no obvious abnormal signal within the femoral head. HE staining in the Yougui Yin medium and high dose groups showed that trabecular bone was coarse and arranged regularly, most of the bone cells were normal, and empty bone lacunae were less. Conclusion:The protective effect of Yougui Yin on SANFH rats may be related to the inhibition of Wnt/β-catenin signaling pathway.

Case-control study on robot-assisted core decompression and conventional core decompression for early necrosis of femoral head / 中国骨伤

OBJECTIVE@#To compare clinical effect of robot-assisted core decompression and conventional core decompression in treating ARCO Ⅰ stage necrosis of femoral head.@*METHODS@#A retrospective analysis was performed on 60(unilateral operation) patients who underwent core decompression for femoral head necrosis from February 2018 to February 2020. Among them, 30 patients(30 hips) were underwent robot-assisted core decompression (RCD group), including 19 males and 11 females, aged from 17 to 58 years old with an average of(38.50±10.61) years old;30 patients(30 hips) were underwent traditional core decompression surgery (CCD group), including 20 males and 10 females, aged from 20 to 55 years old with an average of (40.63±10.63) years old. Intraoperative fluoroscopy times, intraoperative blood loss and operation time between two groups, and Harris score, visual analogue scale (VAS) before opertaion and 24 months after operation were compared.@*RESULTS@#All patients were followed up, RCD group followed up from 21 to 26 months with an average of(23.40±1.65) months, CCD group followed up from 21 to 26 months with an average of (23.30±1.66) months, and had no difference between two groups(P>0.05). The number of intraoperative X-ray fluoroscopy, intraoperative blood loss and operative time in RCD group were (9.43±1.14) times, (153.80±22.04) ml, (33.40±1.87) min, respectively;while(19.67±1.32) times, (165.04±20.41) ml and (54.75±3.46) min in CCD group respectively;and there were statistical difference between two groups(P<0.05). In addition, there were no statistical difference between two groups in Harris score and VAS at 24 months after operation(P>0.05).@*CONCLUSION@#Compared with conventional core decompression, robot-assisted core decompression could reduce the number of intraoperative fluoroscopy, shorten operation time, and reduce risk of surgery.

Experimental model study of ischemic necrosis induction of the growing femoral head / Estudo do modelo experimental de indução da necrose isquêmica da cabeça femoral em crescimento

ABSTRACT Many experimental models exist to better understand the necrosis of the femoral head etiology, both in terms of the species variety in which necrosis is induced and in the operative techniques used for treatment. Objective: This study has two main objectives, the first is to review the literature concerning experimental models of avascular necrosis of the growing femoral head, the second, to demonstrate the experimental pig model's reproducibility using a pilot study. Methods: This was a bibliographic review to describe the attempts over time to find the best species and technique for induction that would reproduce ischemic necrosis of the growing femoral head in humans. Simultaneously, a pilot study was performed to verify the replication of induction in pigs, the species that has more similarities with the human hip. The pilot's methodological analysis consists of conventional radiology and verification of possible anatomical, pathological changes. Results: In imaging exams; lateral sub-dislocation of the femur head and triangular appearance of the head were observed, characterizing its flattening; in macroscopic examination, the femoral head flattening with femoral neck widening and shortening was identified; in histology, the proliferation of articular cartilage with the presence of vascular granulation regenerative tissue, with osteoclasts and fibrocartilaginous tissue in the metaphyseal femoral neck region was identified. Conclusion: The experimental pig model can be used as a valuable tool for the reproducibility of anatomical, pathological changes in ischemic necrosis of the growing femoral head. The model is reproducible and feasible and can be beneficial for future studies on the anatomical pathology of necrosis of the growing femoral head. Level of Evidence III, Literature Review .

RESUMO Na tentativa de compreender melhor a etiologia da necrose da cabeça femoral, existe uma diversidade de modelos experimentais tanto no que diz respeito à variedade das espécies em que é induzida a necrose quanto nas técnicas operatórias utilizadas para o tratamento. Objetivo: Este trabalho tem fundamentalmente dois objetivos: a revisão da literatura concernente aos modelos experimentais da necrose avascular da cabeça do fêmur em crescimento e demonstrar a reprodutibilidade do modelo experimental do suíno por meio de um estudo piloto. Métodos: Foi realizada uma revisão bibliográfica descrevendo as tentativas ao longo do tempo em buscar qual seria a melhor espécie e técnica para indução que reproduzisse a necrose isquêmica da cabeça do fêmur em crescimento nos humanos. Simultaneamente foi feito um estudo piloto para verificar a replicação da indução na espécie suína, o espécime cujo quadril tem mais similaridades com o humano. A análise metodológica do piloto consiste na radiologia convencional e verificação das possíveis alterações anátomo patológicas. Resultados: Nos exames por imagem, foram observadas sub-luxação lateral da cabeça do fêmur e aparência triangular da cabeça, caracterizando o achatamento da mesma; no exame macroscópico, identificamos o achatamento da cabeça femoral com alargamento e encurtamento do colo; na histologia, identificamos a proliferação da cartilagem articular com presença de tecido regenerativo vascular de granulação, com osteoclastos e tecido fibrocartilaginoso na região metafisária do colo femoral. Conclusão: Podemos inferir que o modelo experimental suíno pode servir como ferramenta valiosa para a reprodutibilidade das alterações anátomo patológicas da necrose isquêmica da cabeça femoral em crescimento. O modelo é reprodutível e factível, servindo para estudos futuros sobre a anátomo patologia da necrose da cabeça do fêmur em crescimento. Nível de Evidência III, Revisão da Literatura .

Characteristics and treatment of acetabular fracture combined with ipsilateral femoral neck fracture / 中华创伤骨科杂志

Objective:To investigate the injury characteristics, treatment strategy and prognosis of acetabular fracture combined with ipsilateral femoral neck fracture.Methods:A retrospective analysis was conducted of the 15 patients with acetabular fracture combined with ipsilateral femoral neck fracture who had been treated from January 2009 to June 2021 at Department of Orthopaedics, The First Hospital Affiliated to Nanjing Medical University. They were 10 males and 5 females, aged from 26 to 68 years (average, 47.1 years). The treatment strategy depended on their injury characteristics. For the 3 patients with incomplete displacement of the femoral neck fracture but no hip dislocation, the femoral neck fracture was treated by closed reduction and internal fixation; for the 7 patients with complete displacement of the femoral neck fracture but no hip dislocation, the femoral neck fracture was treated first by closed reduction and then by open reduction and internal fixation in case the closed reduction had failed; for the 5 patients complicated with hip dislocation (anterior one in 2 cases and posterior one in 3 cases), the femoral neck fracture was treated by open reduction and internal fixation. The acetabular fractures were treated via an appropriate surgical approach depending on their classifications. The operation time, intraoperative bleeding, fracture healing, functional recovery and complications such as postoperative avascular necrosis of the femoral head (NFH) were recorded.Results:In this cohort, the operation time ranged from 170 to 540 min, averaging 210 min, and the amount of intraoperative bleeding from 300 to 7,900 mL, averaging 800 mL. Postoperative X-ray films showed that all acetabular fractures and femoral neck fractures achieved anatomical reduction or satisfactory reduction. All patients were followed up for 1 to 13 years (average, 4 years). One patient had to receive total hip arthroplasty due to nonunion one year after operation, and the fractures in the other 14 patients healed by the first intention. At the last follow-up by the Merle d'Aubigné & Postel scoring, the function of the hip affected was excellent in 3 cases, good in 6 and poor in 6. NFH occurred in 4 cases, of which one had no hip dislocation and 3 had hip dislocation. Ectopic ossification developed in one patient after operation.Conclusions:The incidence of NFH is high in the patients with acetabular fracture combined with ipsilateral femoral neck fracture, especially higher in those complicated with hip dislocation. Treatment strategies should vary according to the injury characteristics. Attention should be paid to protection of the blood supply to the femoral head which significantly improves the prognosis.

The effects of weight-bearing area compression injury of the femoral head on the outcomes of elderly acetabular fractures after open reduction and internal fixation / 中华骨科杂志

Objective:To evaluate the effects of weight-bearing area compression injury of the femoral head on the prognosis of elderly acetabular fractures after open reduction and internal fixation.Methods:A retrospective analysis of 36 elderly patients with acetabular fractures treated with open reduction and internal fixation during January 2014 to January 2018 were conducted. All patients with compression injury of the weight-bearing area of the femoral head, including 22 males and 14 females with 73.2±6.5 years old (range 60-87 years old), were included. The compression injury of weight-bearing area of the femoral head was not treated. According to the Letournel-Judet classification of acetabular fractures, there were 14 cases with both-column, 12 cases with anterior column and posterior hemitransverse, 4 cases with T type, 4 cases with transverse, and 2 cases with posterior column+ posterior wall. A total of 14 cases were accompanied by acetabular joint surface compression, while 29 cases were accompanied by joint dislocation. The Merle d'Aubigné score was used to evaluate the hip function during follow-up. The Matta classification method was used to evaluate the results of acetabular fracture reduction. The Kellgren-Lawrence classification standard and Ficat-Alert staging method were used to evaluate the traumatic arthritis of the hip and femoral head necrosis, respectively. During the follow-up, the femoral head necrosis with stage III, IV, or traumatic arthritis III, IV, or with indications for joint replacement was defined as surgery failure. CT scans of the pelvis were performed before and at 2-5 days after operation. The compression size of the femoral head on the coronal and axial planes of the CT scan was calculated for the compression volume. The compression severity was divided into small (<1 cm 3), medium (1-2 cm 3) and large (>2 cm 3) according to the volume. Binary Logistic regression analysis was used to analyze whether the postoperative measurement of the femoral head compression volume was associated with the risk of surgical failure. Results:All patients were followed up for 34.7±8.9 months (range 25-54 months). There were 7 cases with large compression of femoral head, 14 cases with medium, and 15 cases with small pre-operatively. However, there were 12 cases, 10 cases and 14 cases with large, medium and small at 2-5 days after operation, respectively. Six cases were excellent reduction, 22 cases were good, and 8 cases were poor. Thus, the excellent and good rate was 78% (28/36). At the last follow-up, Merle d'Aubigné score was excellent in 2 cases, good in 8 cases, fair in 5 cases, and poor in 21 cases. The excellent and good rate was 28% (10/36). There were 20 cases with surgery failure with 56% (20/36) failure rate. There were no statistically significant differences in the patient's age, body mass index, operation duration, blood volume, fracture type, fracture reduction, combined acetabular joint surface compression, and combined joint dislocation between the two groups. However, there was a statistically significant difference in the frequency distribution of compression volume in the weight-bearing area of the femoral head after surgery (χ 2=22.047, P<0.001). In patients with large, medium, and small-volume compression of the femoral head weight-bearing area, the surgery failure rates were 92%, 80%, and 7%, respectively. The large and medium-volume compression of the femoral head weight-bearing area were independent risk factors for surgical failure. Conclusion:Open reduction and internal fixation can be used to treat elderly patients with acetabular fractures combined with femoral head compression injury. Despite satisfactory reduction for acetabular fractures, the larger volume of femoral head compression affects the clinical outcomes with extremely high rate of surgical failure within 2 years.

Study on the expression of connexin-43 in steroid-induced osteonecrosis of femoral head and osteoblasts in rats and its regulation mechanism / 中华骨科杂志

Objective:To investigate the expression of connexin-43 (Cx43) in steroid-induced osteonecrosis of femoral head and osteoblasts in rats and its regulation mechanism.Methods:The model of steroid-induced osteonecrosis of femoral head (SIONFH) of rat was established. Micro-CT and HE staining were used to observe the degree of bone trabecular destruction and the incidence of empty lacunae. The expression levels of Cx43 and PI3K/Akt signaling pathway related molecules and osteoblast-related proteins in model group and control group were detected by RT-PCT and Western blot. The osteoblast (OB) of rats was further isolated and cultured in vitro. Under treatment of dexamethasone (Dex), Cx43 expression in OB cells was detected by Western blot and immunofluorescence. Western blot was used to detect the effect of glucocorticoid (GC) on the expression of related molecules of PI3K/Akt/β-catenin signaling pathway. Akt activator (SC79) and PI3K inhibitor (LY294002) were used to study the molecular mechanism of Dex regulation on Cx43 expression in OB cells. The regulatory relationship between β-catenin and Cx43 was investigated by immunoprecipitation and small interfere RNA (siRNA) technology.Results:The model of SIONFH in rats was successfully established, which proved that Cx43 expression level in the SIONFH model group was significantly lower than that in the control group, and the expression level of Cx43 was positively correlated with the expression of PI3K/Akt signaling pathway related molecules and osteoblast-related proteins Runx2, ALP and Collagen I Type (COL). In addition, in vitro culture of isolated rat OB cells, the expression of Cx43, p-PI3K, P-Akt and β-catenin in OB cells decreased gradually as the Dex action time went on. Moreover, SC79 pretreatment could significantly reverse the inhibitory effect of GCs on Cx43 expression, while LY294002 could significantly enhance the inhibitory effect of GCs on Cx43. In addition, the immunoprecipitation results showed that β-catenin expression was closely related to Cx43 expression, and further studies showed that β-catenin-siRNA could significantly down-regulate the expression of Cx43.Conclusion:Under the action of GC, the expression level of Cx43 in bone tissue and OB cells decreased significantly, and the possible mechanism was that GCs inhibited the expression of Cx43 by inhibiting the PI3K/Akt/β-catenin signaling pathway, which laid a new theoretical foundation for the further study of the role of Cx43 in the pathogenesis of steroid-induced femoral head necrosis.

How does containment surgery alter the natural evolution in early stage of Perthes disease / 中华骨科杂志

Objective:Course of evolution observed relatively early Perthes disease in children surgically treated and conservative, explore the significance of early surgical treatment of Perthes disease.Methods:From January 1997 to December 2017, 632 children with Perthes disease were admitted. According to the inclusion and exclusion criteria, a total of 67 children were included in this study. Surgical group: 35 cases, 32 males and 3 females, age ranged from 7.0 to 11.8 years, with an average 8.3±1.0 years old, 21 cases on the left side and 14 cases on the right side. Conservative group: 32 cases, 24 males and 8 females, age ranged from 7.1 to 12.0 years old, with an average of 8.4±1.4 years old, 22 cases on the left side and 10 cases on the right side. The pelvic orthosis and frog position were taken every 3 months, and the evolution of Perthes disease was evaluated by referring to the modified Waldenstr?m staging. In the series of observations, no modified Waldenstr?m IIb stage was found to skip the fragmentation stage. After the healing period, the pelvic orthosis and frog position were evaluated according to the Stulburg classification results, and the ratio of the width of the metaphyseal end of the affected side to the contralateral side and the height of the femoral head epiphysis were measured.Results:The time required to enter stage IIIa, surgical group: range from 0.1 to 1.5 years, with an average of 0.58±0.33 years, conservative group: range from 0.4 to 1.8 years, with an average of 0.96±0.30 years, it takes both to enter the repair phase The time difference was statistically significant ( t=5.259, P<0.05); children whose disease course skipped the fragmentation stage, surgical group: 11 cases (31%), conservative group: 5 cases (16%), the difference is statistically significant ( χ2=22.626, P<0.05). The ratio of the affected side to the uninfected side of the metaphysis: surgical group: range 101%-123%, with an average of 108.0%±6.0%. Conservative group: range 101%-148%, with an average of 115.8%±11.2%. The difference in the ratio between the affected side and the healthy side of the metaphysis was statistically significant ( t=3.450, P<0.05). The ratio of the affected side to the healthy side of the height of the femoral head epiphysis: surgical group: range 61%-96%, with an average of 82.5%±8.2%. Conservative group: range 33%-92%, with an average of 74.7%±1.3%. There was a statistically significant difference in the ratio of the height of the femoral head epiphysis between the affected side and the healthy side ( t=2.921, P<0.05). Stulberg classification, surgical group: Type I hip joints 29 hips, Type II hip joints 6 hips, Type III hips 0 hips; conservative group: Type I hips 16 hips, Type II hips 10 hips, Type III hips 6 hips. There was a statistically significant difference in the Stulberg classification after the two entered stage IV ( Z=3.386, P<0.05). Conclusion:Early surgery changed the natural evolution of Perthes disease. Early surgical treatment shortens the fragmentation period of Perthes disease, so that it enters the repair phase ear-lier, and has the opportunity to skip the late fragmentation period and change its natural course. After healing, the morphological change of the proximal femur is closer to normal.

Clinical and genetic risk factors for glucocorticoid-associated osteonecrosis of the femoral head: a prospective cohort study / 中华骨科杂志

Objective:To perform a prospective cohort study to identify individual susceptibility of glucocorticoid (GC) -associated osteonecrosis of the femoral head (GA-ONFH) and their clinical and genetic risk factors. Methods:The present prospective cohort study enrolled patients who received their first GC therapy between July 2015 and January 2018 at Zhongshan Hospital. All patients did not receive any GC treatment before enrollment. Further, they planned to start GC treatment with the dose (equivalent prednisone) of ≥30 mg/d, lasted ≥3 weeks, or pulse dose ≥200 mg/d, lasted ≥3 d. Blood samples were collected before GC treatment to evaluate bone metabolism and its released factors. Hip MRI was performed at the 1st, 3rd, 6th, 12th and 24th month to diagnose GA-ONFH. All patients were followed-up for ≥2 years. The endpoint was regarded as diagnosis of GA-ONFH or completion of 2 years follow-up. Lasso regression was performed to determine which clinical features were associated with GA-ONFH. A nested case-control sub-cohort (A, n=12) was established prospectively based on the main cohort by 1∶1 matching. Whole exome sequencing was performed to screen differential and functional candidate single nucleotide polymorphisms and insertion-deletions (SNP/InDels). Another sub-cohort (B, n=50) was constructed retrospectively in patients with GA-ONFH and non-ONFH patients received standard high dose GC treatment for more than two years. The candidate SNP/InDels were verified by Sanger sequencing based on the patients from sub-cohort B. Results:A total of 96 patients were enrolled of which 88 of them (32 males and 56 females, mean age 42.30 years) completed follow-up. Eight cases (9.1%) were diagnosed with GA-ONFH. The median time from the start of GC therapy to the diagnosis of ONFH was 53.00(34.00,13.50) days. The baseline characteristics, such as age, sex and body mass index, indicated no significant difference between the ONFH group and the non-ONFH group. The cumulative GC dose of the ONFH patients in the first month was higher than that of non-ONFH [32.74(29.55, 47.05) mg/kg vs. 24.00(21.10, 29.45) mg/kg, Z=-2.410, P=0.016]. However, there was no significant difference of patients who underwent pulse therapy (37.5% vs. 10.0%, adjusted χ 2=2.829, P=0.093). The ratio of serum apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) in patients with ONFH was higher than that in non-ONFH group before GC use [0.95(0.80, 1.50) vs. 0.70(0.60, 0.80), Z=-2.875, P=0.000]. Due to the multicollinearity, Lasso regression model was performed to reduce overfitting. All variables were included in the model. The results suggested that higher ApoB/ApoA1 ratio, lower serum β-c-terminal telopeptide (β-CTX) and higher cumulative GC dose in the first month were the top three risk factors of GA-ONFH. This model had an accuracy of 0.982 in internal validation. Seven differential candidate SNP/InDels were found by whole exome sequencing of sub-cohort A. We further verified these SNP/InDels in sub-cohort B. The patients with COLEC12 mutation (rs2305027, G1816A) were at risk of GA-ONFH ( OR=6.00, 95% CI: 1.17, 30.73). Conclusion:Higher first-month GC dose, lower serum β-CTX level before treatment, higher ApoB/ApoA1 ratio and COLEC12 mutation (rs2305027, G1816A) could increase the risk of GA-ONFH.