Identification of circRNA CDR1as/miR-214-3p regulatory axis in Legg-Calvé-Perthes disease.

BACKGROUND: Legg-Calvé-Perthes disease (LCPD) commonly occurs among adolescents, threatening their health. However, the potential mechanism underlying LCPD remains unclear. miR-214-3p is shown as a critical role in LCPD development with unspecified upstream regulators. METHODS: Levels of miR-214-3p and circCDR1as in healthy controls and LCPD patients were determined by qRT-PCR. The role of circCDR1as/miR-214-3p axis in LCPD was determined by testing the cell viability and apoptosis in TC28 cells and primary chondrocytes. Regulation between circCDR1as and miR-214-3p was examined by RIP and ChIP assays. The inflammatory response and angiogenesis were evaluated by M2 macrophage polarization and HUVECs tumor formation. RESULTS: circCDR1as was overexpressed in LCPD patients with a negative correlation with miR-214-3p. Inhibition of circCDR1as alleviated the cell viability and apoptosis of DEX-treated chondrocytes, stimulated M2 macrophage polarization and angiogenesis. miR-214-3p was proved as a downstream effector to participate in circCDR1as mediated actions. circCDR1as recruited PRC2 complex to epigenetically suppress miR-214-3p. CONCLUSION: Our study illustrated the role and mechanism of circCDR1as in LCPD development by targeting miR-214-3p, highlighting its potential in the therapy for LCPD.

A framework for three-dimensional statistical shape modeling of the proximal femur in Legg-Calvé-Perthes disease.

PURPOSE: The pathomorphology of Legg-Calvé-Perthes disease (LCPD) is a key contributor to poor long-term outcomes such as hip pain, femoroacetabular impingement, and early-onset osteoarthritis. Plain radiographs, commonly used for research and in the clinic, cannot accurately represent the full extent of LCPD deformity. The purpose of this study was to develop and evaluate a methodological framework for three-dimensional (3D) statistical shape modeling (SSM) of the proximal femur in LCPD. METHODS: We developed a framework consisting of three core steps: segmentation, surface mesh preparation, and particle-based correspondence. The framework aims to address challenges in modeling this rare condition, characterized by highly heterogeneous deformities across a wide age range and small sample sizes. We evaluated this framework by producing a SSM from clinical magnetic resonance images of 13 proximal femurs with LCPD deformity from 11 patients between the ages of six and 12 years. RESULTS: After removing differences in scale and pose, the dominant shape modes described morphological features characteristic of LCPD, including a broad and flat femoral head, high-riding greater trochanter, and reduced neck-shaft angle. The first four shape modes were chosen for the evaluation of the model's performance, together describing 87.5% of the overall cohort variance. The SSM was generalizable to unfamiliar examples with an average point-to-point reconstruction error below 1mm. We observed strong Spearman rank correlations (up to 0.79) between some shape modes, 3D measurements of femoral head asphericity, and clinical radiographic metrics. CONCLUSION: In this study, we present a framework, based on SSM, for the objective description of LCPD deformity in three dimensions. Our methods can accurately describe overall shape variation using a small number of parameters, and are a step toward a widely accepted, objective 3D quantification of LCPD deformity.

A retrospective study describing the acetabular consequences of Legg- Calve-Perthes disease.

PURPOSE: Legg Calve Perthes disease (LCPD) is a paediatric hip disorder caused by ischemia of the femoral epiphysis, causing femoral head deformity when untreated. This study aims to determine if previously validated pelvic obliquity radiographic parameters, used for assessing acetabular retroversion in developmental dysplasia of the hip, are applicable to patients with LCPD and its prognostic value. METHOD: A retrospective study of patients with Legg Calve Perthes disease was carried out, analysing 4 pelvic parameters: Ilioischial Angle, Obturator Index, Sharp's Angle and Acetabular Depth-Width Ratio (ADR). The differences between healthy and affected hips were studied, and subsequently, it was assessed whether these parameters have prognostic value in the disease outcome. RESULTS: Statistically significant differences have been obtained in the ilioischial angle, obturator index and ADR, between the affected and healthy hip. However, only the Acetabular Depth-Width Ratio showed predictive value for the disease outcome. CONCLUSION: Although this study revealed differences in pelvic parameters between healthy and diseased hips, with only the ADR showing statistical significance in the disease's evolution and prognosis, further studies with larger sample sizes are necessary.

The prevalence of Legg-Calvé-Perthes disease among paediatric patients with transient synovitis of the hip: a systematic review and meta-analysis.

BACKGROUND: Transient synovitis of the hip is the most common cause of limping in paediatric emergency departments. There is no consensus regarding routine follow-up after hip synovitis among children, and there are no standardized criteria for selecting cases that warrant follow-up due to persistent or recurring symptoms to rule out the possibility of Legg-Calvé-Perthes disease. Delayed treatment of Legg-Calvé-Perthes disease may increase the risk of developing early secondary coxarthrosis. Understanding the prevalence of Legg-Calvé-Perthes disease among paediatric patients with transient synovitis of the hip is of paramount importance and could empower both parents and paediatricians to make well-informed decisions when selecting follow-up care for children, thus ensuring that no cases of Legg-Calvé-Perthes disease are missed among diagnosis paediatric patients with transient synovitis of the hip. The aim of this review was to estimate the prevalence of Legg-Calvé-Perthes disease among paediatric patients with transient synovitis of the hip. METHODS: This study was conducted in strict accordance with the PRISMA guidelines and was registered with PROSPERO. The PubMed, Embase, and Cochrane Library databases were comprehensively searched up to July 2024 to identify relevant studies. The inclusion criteria were as follows: patients diagnosed with transient synovitis of the hip; patients aged up to 18 years; and studies with a minimum of 10 cases of paediatric transient synovitis of the hip. To pool the prevalence rates from individual studies, we utilized a random-effects meta-analysis. To assess the quality of the included studies in detail, we employed the Joanna Briggs Institute's quality assessment checklist. RESULTS: A total of 19 studies were ultimately included for the final analysis, with 2,617 paediatric cases of transient synovitis of the hip. The results of meta-analysis revealed that the pooled prevalence estimate of Legg-Calvé-Perthes disease among all paediatric patients with transient synovitis of the hip was 2.7% (95% CI 1.4-5.1). Significant heterogeneity was observed across the studies included in this analysis (I2 = 79.990%; P = 0.000). The pooled prevalence estimate of Legg-Calvé-Perthes disease among paediatric patients with recurrent or persistent transient synovitis of the hip was 36.3% (95% CI 21.6-54.2). Significant heterogeneity was also observed across the studies included in this analysis (I2 = 51.519%; P = 0.036). Furthermore, the follow-up period varied from 6 weeks to 24 months. The primary diagnostic imaging modality utilized for identifying Perthes disease was X-ray. CONCLUSION: Our study revealed that among paediatric patients with transient synovitis of the hip, routine X-ray follow-up of the hips after 6 weeks to rule out Legg-Calvé-Perthes disease is warranted only in patients who exhibit persistent or recurrent symptoms.

Effectiveness of therapeutic methods for Legg-Calvé-Perthes disease according to staging, limits of conservative treatment: a systematic review with meta-analysis.

Legg-Calvé-Perthes disease (LCPD) is known as a self-limiting pediatric orthopedic pathology that affects the hip due to ischemia with consequent aseptic avascular necrosis of the femoral head. This is a systematic literature review carried out in the databases indexed in the Medical Literature Analysis and Retrieval System Online (MEDLINE) in accordance with the precepts established by the PRISMA methodology (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The aim was to compare the effectiveness of treatment for Legg-Calvé-Perthes disease in relation to its staging: the limits of conservative treatment. Conservative treatment was used in four studies, and most patients under the age of 6.5 had Stulberg I and II results. Older patients, between eight and ten years old, had a relatively better classification when they underwent surgical treatment. In this context, the data collected did not show significant variations; however, it was possible to observe that conservative treatment was more effective in this population, while surgical treatment is better recommended at older ages.

Femoral Head Reduction Osteotomy for Legg-Calvé-Perthes Disease Sequelae: Case Report.

Legg-Calvé-Perthes disease (LCPD) commonly causes sequelae in the hip joint morphology. A common variant is an oversized, nonspherical femoral head, associated with a short femoral neck and elevated greater trochanter, which leads to femoroacetabular impingement (FAI). The innovative Ganz technique for surgical hip dislocation opened up new treatment possibilities for FAI, including LCPD sequelae, without increasing the risk of avascular necrosis of the femoral head. In the ellipsoid coxa magna resulting from LCPD, joint wear is more accentuated in the central portion of the femoral head; the lateral third remains intact as it does not articulate with the acetabulum. A femoral head reduction osteotomy technique developed for such cases resects the damaged portion of the femoral head and restores its sphericity. Short-term outcomes are encouraging. The present case report presents a patient with LCPD sequelae submitted to a femoral head reduction osteotomy.

Approaching total hip arthroplasty after Legg-Calvé-Perthes disease: A case series and literature review.

Due to femoral head-neck deformities and hip joint incongruence, patients with Legg-Calvé-Perthes Disease (LCPD) commonly require total hip arthroplasty (THA) in the fifth and sixth decades of life. These patients present additional challenges to arthroplasty surgeons not only because of their complicated hip anatomy but also because patients may have undergone prior operative procedures in childhood and thus present with pre-existing proximal femoral deformities. THA in LCPD patients can be associated with peri-operative complications such as fracture or nerve injury, and the rate of reoperation has been reported to be higher in the LCPD population as compared to the general population undergoing THA. Despite this, multiple case reports and studies have shown the relative long-term success of THA in patients with history of LCPD. In particular, uncemented modular stems are a commonly used implant choice in such cases. This article reviews and discusses the technical considerations for THA in patients with LCPD and highlights three such cases.

Generation and characterization of mesenchymal stem cells from the affected femoral heads of dogs with Legg Calvé Perthes disease.

Background: Canine Legg Calvé Perthes disease (LCPD) occurs during the growth period, and the cause of ischemic necrosis of the femoral head during growth remains unclear. If LCPD-affected femoral head-derived mesenchymal stem cells (LCPD-MSCs) can be generated, they can be used as a new tool for the pathophysiological analysis of canine LCPD. Aim: To generate affected femoral head-derived mesenchymal stem cells (MSCs) from dogs with LCPD and investigate the mRNA expression levels of angiogenesis-related factors and osteogenic differentiation potency of LCPD-MSCs. Methods: This study was performed using affected femoral heads from dogs diagnosed with LCPD and underwent femoral head and neck ostectomy. The necrotic tissue was harvested from the LCPD-affected femoral head and cultured statically (LCPD group, n = 6). Canine bone marrow-derived MSCs (BM-MSCs) were used as controls (control group, n = 6). First, the morphology of the cultured cells was observed, and the expression of CD29, CD34, CD44, CD45, CD90, and major histocompatibility complex class II was analyzed using flow cytometry. Additionally, the trilineage differentiation potency of the LCPD-affected head-derived adherent cells was examined. Furthermore, the expression levels of HIF1A, VEGFA, VEGFB, and PDGFB mRNAs and the bone differentiation potency of LCPD-affected head-derived adherent cells were investigated. Results: LCPD-affected femoral head-derived adherent cells showed a fibroblast-like morphology, and the expression of cell surface antigens was similar to that of BM-MSCs. In addition, LCPD-affected femoral head-derived adherent cells showed the same trilineage differentiation potency as BM-MSCs and were consistent with MSC characteristics. Furthermore, the mRNA expression levels of angiogenesis-related factors could be objectively measured in LCPD-MSCs and those MSCs had bone differentiation potency. Conclusion: In the present study, canine LCPD-MSCs were successfully generated, suggesting their usefulness as a tool for pathological analysis of LCPD in dogs.

Detection of early metaphyseal changes in a piglet model of Legg-Calvé-Perthes disease using quantitative mapping of MRI relaxation times.

Legg-Calvé-Perthes disease (LCPD) is a childhood hip disorder characterized by ischemic injury to the epiphysis of the femoral head, but changes to the metaphysis have also been implicated in its pathogenesis. Quantitative magnetic resonance imaging (MRI) relaxation time mapping techniques are potentially useful to detect injury in LCPD, but studies to date have focused on the epiphysis. The purpose of this study was to assess whether T2, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation times can detect early metaphyseal changes in an LCPD piglet model. Complete epiphyseal ischemia of one femoral head was surgically induced and confirmed using contrast-enhanced MRI in n = 10 6-week-old piglets; the contralateral side was unoperated. The bilateral hips were imaged 1 week after surgery in vivo at 3T MRI using relaxation time mapping and contrast-enhanced MRI. Relaxation times and thicknesses of the metaphyseal primary and secondary spongiosa were measured and compared between the ischemic and contralateral-control femoral heads using paired t-tests. In the ischemic femoral heads, T2 relaxation times were significantly increased in the primary spongiosa (6.7 ± 9.8 ms, p = 0.029), and T2, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation times were significantly decreased in the secondary spongiosa (respectively: -13.3 ± 9.3 ms, p = 0.013; -32 ± 23 ms, p < 0.001; -43 ± 41 ms, p = 0.009; and -39 ± 13 ms, p < 0.001). The secondary spongiosa thickness was also significantly decreased in the ischemic femoral heads (p < 0.001). In conclusion, T2, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation time mapping techniques can detect early changes in the metaphysis following ischemic injury to the epiphysis of the femoral head in a piglet model of LCPD.

Proximal femoral varus osteotomy for Legg-Calvé-Perthes disease: Do age and lateral pillar classifications influence short-to-mid-term clinical and radiological outcomes?

INTRODUCTION: Proximal femoral varus osteotomy (FVO) is one of the most used treatment methods with acceptable outcomes for Legg-Calvé-Perthes disease (LCPD). We aimed to investigate the influence of age at disease onset and the Lateral Pillar classification on clinical and radiological outcomes of FVO surgery LCPD patients between 6-12years of age. HYPOTHESIS: Proximal FVO surgery in the early fragmentation phase of LCPD patients led to acceptable clinical and radiographic outcomes in a 3-year follow-up, regardless of preoperative age and Herring type. MATERIAL AND METHODS: Fifty patients with LCPD (Herring groups B, B/C, and C) who underwent FVO were retrospectively reviewed. We evaluated radiological [center-edge angle, extrusion index, epiphyseal index, acetabular index, articulo-trochanteric distance (ATD)] and clinical [hip abduction range of motion (ROM), Trendelenburg sign, pain, and Harris hip score (HHS)] outcomes with a follow-up of 37.3±10.5months (range: 24-180months). Finally, the overall treatment outcome was assessed using the Stulberg classification. RESULTS: The ROC curve analysis did not reveal any significant relationship between age and clinical or radiological outcomes, and there was no predictable age cut-off for surgical outcomes (p=0.13). No significant difference was found in Stulberg classification at the follow-up between patients with type B, B/C, and C of the lateral pillar (p>0.05). DISCUSSION: Our results demonstrated that open-wedge proximal FVO surgery in the early fragmentation phase of LCPD patients led to acceptable clinical and radiographic outcomes in a 3-year follow-up. Each sample of our study was very small and a lot of variables were measured, making this result not adequately strong enough to draw a robust conclusion. However, FVO surgery remains a possible suggestion for patients in the early fragmentation phase, and age and lateral pillar type may not be limiting factors. LEVEL OF EVIDENCE: IV; therapeutic retrospective cohort.

Bone Remodeling and Bone Structural Genes in Legg-Calvé-Perthes Disease: The OPG rs2073618 and IL-6 rs1800795 Are Associated with High Risk in Mexican Patients.

Legg-Calve-Perthes disease (LCPD) is an idiopathic avascular necrosis of the pediatric femoral head. Bone remodeling and bone structural genes have the potential to contribute to the progression of LCPD when there is disequilibrium between bone resorption and bone formation. A case-control study was performed to search for associations of several common polymorphisms in the genes Receptor Activator for Nuclear Factor κappa B (RANK), Receptor Activator for Nuclear Factor κappa B Ligand (RANKL), osteoprotegerin (OPG), interleukin (IL)-6, and type 1 collagen (COL1A1) with LCPD susceptibility in Mexican children. A total of 23 children with LCPD and 46 healthy controls were genotyped for seven polymorphisms (rs3018362, rs12585014, rs2073618, rs1800795, rs1800796, rs1800012, and rs2586498) in the RANK, RANKL, OPG, IL-6, and COL1A1 genes by real-time polymerase chain reaction with TaqMan probes. The variant allele (C) of IL-6 rs1800795 was associated with increased risk of LCPD (odds ratio [OR]: 3.8, 95% confidence interval [CI]: [1.08-13.54], p = 0.033), adjusting data by body mass index (BMI) and coagulation factor V (FV), the association with increased risk remained (OR: 4.9, 95% CI: [1.14-21.04], p = 0.025). The OPG polymorphism rs2073618, specifically GC-GG carriers, was associated with a more than fourfold increased risk of developing LCPD (OR: 4.34, 95% CI: [1.04-18.12], p = 0.033) when data were adjusted by BMI-FV. There was no significant association between RANK rs3018362, RANKL rs12585014, IL-6 rs1800796, COL1A1 rs1800012, and rs2586498 polymorphisms and LCPD in a sample of Mexican children. The rs1800975 and rs2037618 polymorphisms in the IL-6 and OPG genes, respectively, are informative markers of increased risk of LCPD in Mexican children.

The Effect of Vitamin D Deficiency as a Risk Factor of Early Fragmentation in Legg-Calve-Perthes Disease: A Prospective Study.

INTRODUCTION: Legg-Calve-Perthes disease (LCPD) is a disorder involving the hips in young children of preschool and school-going age groups, more common in 4-8 years. The insufficient blood supply to the femoral head is the main reason behind various etiologic theories. Multiple factors affect the natural progression of the disease. The natural progression of the disease involves early avascular necrosis, fragmentation, reconstitution, and healed stages. In the fragmentation stage, the bony epiphysis begins to fragment, and the subchondral radiolucent zone (crescent sign) is the result of a subchondral stress fracture, which later on determines the extent of a necrotic fragment of the femoral head. These changes later contribute to changes in the shape of the femur head and the extent of deformity. As vitamin D plays a vital role in the onset of the fragmentation stage, we conducted a study to assess the effect of vitamin D deficiency as a risk factor for early fragmentation in Legg-Calve-Perthes disease. METHODS: In our study, 50 patients aged 4-12 years were examined over three years and classified according to Catterall and Herring's lateral pillar classification; the length of the fragmentation stage and the vitamin D level were considered. A vitamin D level of less than 20 ng/mL was labeled as the deficient group, 20-30 ng/mL as the insufficient group, and more than 30 ng/mL as the sufficient (normal) group. RESULTS: The critical fragmentation stage was significantly longer (more than 12 months) in vitamin D deficiency (34%), leading to a higher risk of deformity and extrusion of the femoral head, which led to higher rates of surgical intervention and containment procedures. CONCLUSION: The fragmentation stage is critical in the course of LCPD. Vitamin D levels play a vital role in predicting the prognostic of LCPD, and it should be measured in all patients of LCPD. Patients with normal vitamin D levels have a comparatively shorter fragmentation stage duration than patients with insufficient or deficient levels, leading to a lesser duration of femoral head damage.

OSTEOCHONDRITIS DISSECANS OF THE HIP IN LEGG-CALVÉ-PERTHES DISEASE: CASE REPORT AND REVIEW.

Introduction: Legg-Calvé-Perthes disease (LCPD) is the idiopathic osteonecrosis of the capital femoral epiphysis in children. It is a self-healing condition, and the morphology of the hip may vary according to the severity of the disease, among several other factors. The treatment focuses on attempts to prevent femoral head collapse, obtain functional hip motion recovery, and reduce pain. Osteochondritis Dissecans (OCD) of the femoral head has been reported in 2% to 7% of patients diagnosed with healed LCPD. Although OCD may remain asymptomatic, the osteochondral fragment has the potential to become unstable, evolving into symptoms of pain, locking, catching, and snapping. Case report: We present a case report of a ten-year-old boy with an OCD lesion following LCPD who underwent effective osteochondral fixation through the surgical hip dislocation approach. The patient evolved to excellent functional recovery at 1 year post-operatively. Discussion: The surgical hip dislocation approach allows anatomical fixation of the OCD fragment, as well as improvement of hip biomechanics, decreasing pain, improving range of motion and joint congruency, and preserving the native articular cartilage. It also gives the surgeon the opportunity to assess hip stability, femoroacetabular impingement and labral tears, allowing a wide variety of options for the treatment of the healed LCPD. Level of Evidence IV; Type of study Case Report.

Introdução: A Doença de Legg-Calvé-Perthes (DLCP) é a osteonecrose idiopática da epífise femoral proximal em crianças. É uma condição auto resolutiva, porém a morfologia final do quadril pode variar de acordo com a gravidade da doença. O tratamento concentra-se na tentativa de prevenir o colapso da cabeça femoral, obtendo recuperação funcional do movimento do quadril e redução da dor. A osteocondrite dissecante (OCD) da cabeça femoral foi relatada em 2% a 7% dos pacientes diagnosticados com DLCP já curada. Embora a OCD possa permanecer assintomática, o fragmento osteocondral tem potencial para se tornar instável, evoluindo para sintomas de dor, bloqueio, impacto e estalido. Relato de caso: Apresentamos o relato de caso de um menino de 10 anos com OCD da cabeça femoral após DLCP, submetido à fixação osteocondral do fragmento por meio da abordagem cirúrgica de luxação do quadril. O paciente evoluiu com excelente recuperação funcional 1 ano após a cirurgia. Discussão: A abordagem cirúrgica da luxação do quadril permite a fixação anatômica do fragmento da OCD, bem como a melhora da biomecânica do quadril, diminuindo a dor, melhorando a amplitude de movimento e a congruência articular e preservando a cartilagem articular nativa. Também dá ao cirurgião a oportunidade de avaliar a estabilidade do quadril, impacto femoroacetabular e lesões labrais, permitindo uma ampla variedade de opções para o tratamento das sequelas da DLCP. Nível de evidência IV; tipo de estudo Relato de Casos.

Global trends in the research on Legg-Calve-Perthes disease in Web of Science.

Background: Legg-Calve-Perthes disease (LCPD) is a form of idiopathic femoral head necrosis that can lead to permanent femoral head deformities and premature osteoarthritis in children under the age of 15. Its pathogenesis is utterly and remains to be clarified. Although many research publications on LCPD have emerged during the last few decades, few systematic bibliometric analyses of these articles have been reported. Methods: A bibliometric analysis was performed to investigate the development processes and hotspots, as well as the collaboration and influence among countries, institutions, authors, journals, and keywords of papers relevant to LCPD from the Web of Science Core Collection (WoSCC) during the period from 1 January 2000 to 30 June 2023. Results: A total of 2,205 researchers from 916 institutions across 53 countries/regions have contributed to 673 papers published in 199 academic journals. The research on LCPD has shown significant fluctuations but a gradual increase in the number of articles published over the last two decades. The United States leads in the number of publications of LCPD, with the Texas Scottish Rite Hospital for Children being the most productive institution. English, as the most widely used language in the world, was undoubtedly the most popular language. Herring JA, who acted as both the corresponding and first author, has contributed to the most co-cited papers published. The most number of LCPD papers are published in the Journal of Pediatric Orthopaedics, whereas the Journal of Bone and Joint Surgery American Volume garnered the highest total citations, indicating the great importance of these two journals in the field of orthopedics. The most frequently used keywords in published articles were related to the symptoms, mechanisms, and prognosis, revealing the research focus of most scholars. Conclusion: Our research described the development trends and hotspots in the research field of LCPD and will help researchers make better decisions.

Prediction of the active compounds and mechanism of Biochanin A in the treatment of Legg-Calvé-Perthes disease based on network pharmacology and molecular docking.

BACKGROUND: Legg-Calvé-Perthes disease is a special self-limited disease in pediatric orthopedics with a high disability rate and a long-term course, and there is still no clear and effective therapeutic drug in clinic. This study aimed to investigate the potential efficacy of biochanin A, a kind of oxygen-methylated isoflavone compound, in treating Perthes disease based on network pharmacology, molecular docking and in vitro experiments. METHODS: IL-6 was used to stimulate human umbilical vein endothelial cells to construct endothelial cell dysfunction model. We demonstrated whether biochanin A could alleviate endothelial dysfunction through CCK8 assay, immunofluorescence. Targets of biochanin A from pharmMappeer, SWISS, and TargetNet databases were screened. Targets of endothelial dysfunction were obtained from Genecards and OMIM databases. Protein-protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomics analyses were used to analyze the potential target and the key pathway of the anti-endothelial dysfunction activity of biochanin A. To validate the potential target-drug interactions, molecular docking and molecular dynamics simulations were performed and the result was proved by western blot. RESULTS: It was found that biochanin A can promote the expression of ZO-1, reduce the expression of ICAM-1, which means improving endothelial dysfunction. A total of 585 targets of biochanin A from pharmMappeer, SWISS, and TargetNet databases were screened. A total of 10,832 targets of endothelial dysfunction were obtained from Genecards and OMIM databases. A total of 527 overlapping targets of endothelial dysfunction and biochanin A were obtained. AKT1, TNF-α, VCAM1, ICAM1, and NOS3 might be the key targets of the anti-endothelial dysfunction activity of biochanin A, and the key pathways might be PI3K-Akt and TNF signaling pathways. Molecular docking results indicated that the AKT1 and TNF-α had the highest affinity binding with biochanin A. CONCLUSION: This study indicates that biochanin A can target AKT1 and TNF-α to alleviate endothelial dysfunction induced by IL-6 in Perthes disease, which provides a theoretical basis for the treatment of Perthes disease by using biochanin A.

Fully automatic system to detect and segment the proximal femur in pelvic radiographic images for Legg-Calvé-Perthes disease.

This study aimed to develop a method using computer vision techniques to accurately detect and delineate the proximal femur in radiographs of Legg-Calvé-Perthes disease (LCPD) patients. Currently, evaluating femoral head deformity, a crucial predictor of LCPD outcomes, relies on unreliable categorical and qualitative classifications. To address this limitation, we employed the pretrained object detection model YOLOv5 to detect the proximal femur on over 2000 radiographs, including images of shoulders and chests, to enhance robustness and generalizability. Subsequently, we utilized the U-Net convolutional neural network architecture for image segmentation of the proximal femur in more than 800 manually annotated images of stage IV LCPD. The results demonstrate outstanding performance, with the object detection model achieving high accuracy (mean average precision of 0.99) and the segmentation model attaining an accuracy score of 91%, dice coefficient of 0.75, and binary IoU score of 0.85 on the held-out test set. The proposed fully automatic proximal femur detection and segmentation system offers a promising approach to accurately detect and delineate the proximal femoral bone contour in radiographic images, which is essential for further image analysis in LCPD patients. Clinical significance: This study highlights the potential of computer vision techniques for enhancing the reliability of Legg-Calvé-Perthes disease staging and outcome prediction.

Osteochondritis dissecans of the hip in legg-calvé-perthes disease: case report and review / Osteocondrite dissecante do quadril na doença de legg-calvé-perthes: relato de caso e revisão

ABSTRACT Introduction: Legg-Calvé-Perthes disease (LCPD) is the idiopathic osteonecrosis of the capital femoral epiphysis in children. It is a self-healing condition, and the morphology of the hip may vary according to the severity of the disease, among several other factors. The treatment focuses on attempts to prevent femoral head collapse, obtain functional hip motion recovery, and reduce pain. Osteochondritis Dissecans (OCD) of the femoral head has been reported in 2% to 7% of patients diagnosed with healed LCPD. Although OCD may remain asymptomatic, the osteochondral fragment has the potential to become unstable, evolving into symptoms of pain, locking, catching, and snapping. Case report: We present a case report of a ten-year-old boy with an OCD lesion following LCPD who underwent effective osteochondral fixation through the surgical hip dislocation approach. The patient evolved to excellent functional recovery at 1 year post-operatively. Discussion: The surgical hip dislocation approach allows anatomical fixation of the OCD fragment, as well as improvement of hip biomechanics, decreasing pain, improving range of motion and joint congruency, and preserving the native articular cartilage. It also gives the surgeon the opportunity to assess hip stability, femoroacetabular impingement and labral tears, allowing a wide variety of options for the treatment of the healed LCPD. Level of Evidence IV; Type of study Case Report.

RESUMO Introdução: A Doença de Legg-Calvé-Perthes (DLCP) é a osteonecrose idiopática da epífise femoral proximal em crianças. É uma condição auto resolutiva, porém a morfologia final do quadril pode variar de acordo com a gravidade da doença. O tratamento concentra-se na tentativa de prevenir o colapso da cabeça femoral, obtendo recuperação funcional do movimento do quadril e redução da dor. A osteocondrite dissecante (OCD) da cabeça femoral foi relatada em 2% a 7% dos pacientes diagnosticados com DLCP já curada. Embora a OCD possa permanecer assintomática, o fragmento osteocondral tem potencial para se tornar instável, evoluindo para sintomas de dor, bloqueio, impacto e estalido. Relato de caso: Apresentamos o relato de caso de um menino de 10 anos com OCD da cabeça femoral após DLCP, submetido à fixação osteocondral do fragmento por meio da abordagem cirúrgica de luxação do quadril. O paciente evoluiu com excelente recuperação funcional 1 ano após a cirurgia. Discussão: A abordagem cirúrgica da luxação do quadril permite a fixação anatômica do fragmento da OCD, bem como a melhora da biomecânica do quadril, diminuindo a dor, melhorando a amplitude de movimento e a congruência articular e preservando a cartilagem articular nativa. Também dá ao cirurgião a oportunidade de avaliar a estabilidade do quadril, impacto femoroacetabular e lesões labrais, permitindo uma ampla variedade de opções para o tratamento das sequelas da DLCP. Nível de evidência IV; tipo de estudo Relato de Casos.

Animal Model Standardization for Studying Avascular Necrosis of the Femoral Head in Legg-Calvé-Perthes Disease.

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 2 nd , 4 th , 6 th , and 8 th 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-ß1 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-ß1 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 Evidence V. Diagnostic studies.

Epidemiology, natural evolution, pathogenesis, clinical spectrum, and management of Legg-Calvé-Perthes.

Background: Legg-Calvé-Perthes disease is a self-limiting disorder that develops in children following interruption of the blood supply to the capital femoral epiphysis. This review outlines the current knowledge on the epidemiology, natural evolution, clinical spectrum, and management of the disease. Methods: The literature pertaining to these aspects of the disease were studied and summarized in this review. Results: Epidemiological studies suggest that environmental factors contribute to the causation of the disease. Incidence rates monitored over time indicate that the incidence of Legg-Calvé-Perthes disease is declining. The natural evolution followed on sequential plain radiographs enables division of the disease into Stages Ia, Ib, IIa, IIb, IIIa, IIIb, and IV. Reversible deformation of the capital occurs in Stages Ia-IIa simply on standing while irreversible deformation may occur in Stages IIb and IIIa. Treatment of Legg-Calvé-Perthes disease in Stages Ia-IIa aims to prevent the femoral head from getting deformed by containment and avoidance of weight-bearing. In Stages IIb and IIIa, treatment aims to remedy the effects of early irreversible deformation of the femoral head. In Stage IIIb and IV, treatment is directed to correcting the altered shape of the femoral head. The impression that these treatment methods are helpful is based on poor quality evidence. Conclusion: There is an urgent need to undertake Level I studies to establish the efficacy of currently treatment. Level of evidence: level V.

Long-Term Outcomes at Skeletal Maturity of Combined Pelvic and Femoral Osteotomy for the Treatment of Legg-Calve-Perthes Disease.

Surgical treatment for Legg-Calve-Perthes disease (LCPD) is recommended for older children with moderate to severe disease. We sought to determine whether double osteotomies lead to improved radiologic outcomes compared to reported non-operative outcomes. Patients older than 6 years of age diagnosed with LCPD lateral pillar B or C who were treated with pelvic and femoral osteotomies were included. Radiologic outcomes and leg-length discrepancies were assessed using the Stulberg classification and were compared with the current literature. Fifteen hips in fourteen patients were treated with double osteotomy for LCPD, and seven had lateral pillar C disease (47%). The mean age at surgery was 8.6 years (range, 7.2-10.4) and the mean age at follow-up was 20.2 years (range, 14.2-35.6). At a mean 11.6-year follow-up (range: 6.3-25.2), double osteotomy resulted in 40% of patients having Stulberg I/II scores, 27% having Stulberg III scores, and 33% having Stulberg IV/V scores. The mean leg-length discrepancy was 1.4 cm in lateral pillar C patients compared to 0.8 cm in lateral pillar B patients. Four patients underwent additional surgeries, including two who required total hip arthroplasty. Double osteotomy as an alternative surgical procedure for the treatment of LCPD did not show improved outcomes when compared to historic non-operative cohorts.