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.

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.

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.

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.

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.

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.

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.

Does Acetabulum Remodel Following Varus Derotation Osteotomy for Perthes' Disease?

Objective We investigated the effect of disease stage, patient's age and final contour of femoral head on acetabulum contour following varus derotation osteotomy of proximal femur (VDRO) in unilateral Perthes's disease. Methods The study is a retrospective analysis of case records of 23 children aged ≥6 years with unilateral Perthes' disease who underwent primary VDRO procedure for containment. Acetabular index (AI) and center edge angle (CEA) were calculated bilaterally in preoperative and follow-up radiographs and compared statistically. Results There were 15 boys and 8 girls. Six hips were in Ib, 8 in IIa and 9 in IIb modified Waldenström stage while undergoing VDRO. The mean age at surgical intervention was 8.7 years. The mean follow-up duration was 3.5 years. All femoral heads were healed at final follow-up and the final Stulberg grades were I = 3, II = 8, III = 7, IV = 5. A significant acetabular dysplasia on the affected side was present preoperatively. At follow-up, the patients operated had significantly raised AI and reduced CEA. There was no significant acetabular remodeling of the affected hips at follow-up even in children operated at younger age (< 8 years) or early stages (stage Ib or IIa). The acetabulum remodeling did not correspond to the final Stulberg grade as well. Conclusion Acetabulum was found involved in early stages of Perthes' disease. Varus derotation femoral osteotomy for the diseased hip showed no significant improvement in acetabular dysplasia even when operated in early disease stages or younger age group. Residual acetabular changes were also noted even with favorable Stulberg grades.

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.

Trends in the Use of Total Hip Arthroplasty in the Pediatric Population: A Review of the Literature.

Current literature shows that the utilization of total hip arthroplasty (THA) to address pediatric hip pathology has seen a significant rise worldwide in recent decades. However, performing THA in pediatric patients presents unique challenges due to their increased activity levels, varying skeletal maturity, and diverse medical conditions. These challenges have relegated THA to a secondary option for young patients. Nonetheless, despite these difficulties, recent studies have demonstrated a growing prevalence of THA in pediatrics. Consequently, there is an urgent need for a comprehensive review of the existing literature on this topic. In this study, we examined large database and single-institution studies involving pediatric patients aged 21 years and under who underwent THA. The primary indications for THA in this population were osteoarthritis, osteonecrosis, and inflammatory arthritis. To ensure informed decision-making for pediatric patients, it is crucial to gather consolidated information on trends and outcomes related to THA indications. This review aims to provide insights into these trends and facilitate better decision-making for the treatment of pediatric patients.

Association between Polymorphism eNOS4, tPA, Factor V Leiden, Prothrombin, and Methylenetetrahydrofolate Reductase and the Occurrence of Legg-Calvé-Perthes Disease.

BACKGROUND: Legg-Calvé-Perthes (LCPD) disease is a complex condition affecting the femoral head's epiphysis in children. It occurs with a prevalence ranging from 0.4 to 29.0 cases per 100,000 children under the age of 15. It involves various factors, including genes associated with coagulation and fibrinolysis, pro-inflammatory factors, and vasoactive substances. METHODS: We investigated the relationship between genetic mutations associated with coagulation and vascular disorders and the occurrence of LCPD in Polish patients. We performed a study involving 25 patients with LCPD and 100 healthy controls. All subjects were genotyped for eNOS4, Factor V Leiden, prothrombin, tPA25, and MTHFR polymorphism. RESULTS: The analysis revealed that the frequencies of eNOS4 genotypes were significantly different in LCPD patients than in the control group (p = 0.018). The frequencies of 4a allele were significantly higher in patients with LCPD than in the healthy population (26% vs. 9%, p = 0.0012). There were no significant differences in genotype and allele frequencies for Factor V Leiden, prothrombin tPA 25, and MTHFR gene polymorphisms between patients with LCPD and the controls. CONCLUSIONS: Genotype and allele frequencies of eNOS4 were significantly higher in patients with LCPD. These findings suggest a potential association between the eNOS gene polymorphism and an increased risk of developing LCPD.

Interleukin-6 receptor blockade improves bone healing following ischemic osteonecrosis in adolescent mice.

Objective: Juvenile ischemic osteonecrosis (JIO) of the femoral head is one of the most serious hip disorders causing a permanent deformity of the femoral head in childhood. We recently reported that interleukin 6 (IL-6) is significantly increased in the hip synovial fluid of patients with JIO and that articular chondrocytes are primary source of IL-6. Adolescent JIO is particularly challenging to treat and has poor outcome. This study determined if IL-6 receptor blockade prevents bone loss and improves the bone healing in adolescent JIO. Method: Adolescent mice (12-week-old) surgically induced with JIO were treated with either saline or MR16-1, an IL-6 receptor blocker. Results: Micro-CT assessment showed significantly increased bone volume (p â€‹< â€‹0.001, Cohen's d â€‹= â€‹2.0) and trabecular bone thickness (p â€‹< â€‹0.001, d â€‹= â€‹2.3) after the MR16-1 treatment. Histomorphometric assessment showed significantly increased osteoblast number (p â€‹< â€‹0.01, d â€‹= â€‹2.3), bone formation rate (p â€‹< â€‹0.01, d â€‹= â€‹4.3), and mineral apposition rate (p â€‹< â€‹0.01, d â€‹= â€‹4.1) after the MR16-1 treatment. The number of osteoclasts was unchanged. Histologic assessment showed significantly increased revascularization (p â€‹< â€‹0.01) and restoration of the necrotic marrow with new hematopoietic bone marrow (p â€‹< â€‹0.01). Vascular endothelial growth factor (VEGF) expression was increased in the revascularized area and the articular cartilage, and in the cultured chondrocytes treated with IL-6 receptor inhibitor. Conclusion: IL-6 blockade in adolescent mice with JIO enhanced bone formation and revascularization. The findings suggest IL-6 receptor blocker as a potential medical therapy for adolescent JIO.

Does Acetabulum Remodel Following Varus Derotation Osteotomy for Perthes' Disease? / O acetábulo sofre remodelamento após a osteotomia derrotatória varizante em pacientes com doença de Perthes?

Abstract Objective We investigated the effect of disease stage, patient's age and final contour of femoral head on acetabulum contour following varus derotation osteotomy of proximal femur (VDRO) in unilateral Perthes's disease. Methods The study is a retrospective analysis of case records of 23 children aged ≥6 years with unilateral Perthes' disease who underwent primary VDRO procedure for containment. Acetabular index (AI) and center edge angle (CEA) were calculated bilaterally in preoperative and follow-up radiographs and compared statistically. Results There were 15 boys and 8 girls. Six hips were in Ib, 8 in IIa and 9 in IIb modified Waldenström stage while undergoing VDRO. The mean age at surgical intervention was 8.7 years. The mean follow-up duration was 3.5 years. All femoral heads were healed at final follow-up and the final Stulberg grades were I = 3, II = 8, III = 7, IV = 5. A significant acetabular dysplasia on the affected side was present preoperatively. At follow-up, the patients operated had significantly raised AI and reduced CEA. There was no significant acetabular remodeling of the affected hips at follow-up even in children operated at younger age (< 8 years) or early stages (stage Ib or IIa). The acetabulum remodeling did not correspond to the final Stulberg grade as well. Conclusion Acetabulum was found involved in early stages of Perthes' disease. Varus derotation femoral osteotomy for the diseased hip showed no significant improvement in acetabular dysplasia even when operated in early disease stages or younger age group. Residual acetabular changes were also noted even with favorable Stulberg grades.

Resumo Objetivo Investigamos o efeito do estágio da doença, idade do paciente e contorno final da cabeça femoral no contorno do acetábulo após a osteotomia derrotatória varizante (VDRO) do fêmur proximal na doença de Perthes unilateral. Métodos O estudo é uma análise retrospectiva de prontuários de 23 crianças com idade ≥ 6 anos com doença de Perthes unilateral que foram submetidas ao procedimento primário de VDRO para contenção. O índice acetabular (AI) e o ângulo da borda central (CEA) foram calculados bilateralmente em radiografias pré-operatórias e de acompanhamento e submetidos à comparação estatística. Resultados Os pacientes eram 15 meninos e oito meninas. À VDRO, seis quadris estavam no estágio de Waldenström modificado Ib, oito no estágio IIa e nove no estágio IIb. A média de idade à intervenção cirúrgica foi de 8,7 anos. A duração média do acompanhamento foi de 3,5 anos. Todas as cabeças femorais estavam consolidadas no último acompanhamento e os graus finais de Stulberg foram I = 3, II = 8, III = 7 e IV = 5. Havia displasia acetabular significativa do lado acometido no período pré-operatório. No acompanhamento, os pacientes operados apresentaram elevação significativa de AI e redução de CEA. Não houve remodelamento acetabular significativo nos quadris acometidos durante o acompanhamento, mesmo em crianças operadas em idade menor (< 8 anos) ou estágios iniciais (estágio Ib ou IIa). O remodelamento do acetábulo também não correspondeu ao grau final de Stulberg. Conclusão A VDRO do fêmur do quadril acometido não levou à melhora significativa da displasia acetabular, mesmo quando a cirurgia foi realizada nos estágios iniciais da doença ou em pacientes mais jovens. Alterações acetabulares residuais também foram observadas mesmo com graus de Stulberg favoráveis.

Clinical Outcomes of Open-Wedge Varus Derotation Osteotomy in Legg-Calve-Perthes Disease Among 6-12-Year-Old Children.

Background Legg-Calve-Perthes (LCP) disease during early childhood might lead to impaired blood circulation to the femoral head causing osteoarthritis and avascular necrosis of the femoral head. In most cases of children diagnosed after the age of nine years, the progression of LCP disease is associated with poor outcomes causing disability. This study aimed to evaluate the clinical and radiological outcomes of varus derotation osteotomy in children with LCD disease with a late presentation at 6-12 years of age. Methodology This prospective study was performed among 25 6-12-year-old children who were diagnosed with LCD disease. Children were classified per Herring's Lateral Pillar and Catterall classification. They were treated with open-wedge varus derotation osteotomy, and clinical, radiological, and functional parameters were assessed postoperatively. The postoperative grading was done using the Catterall classification. Results In this study, significant improvement in the postoperative mean Harris Hip Score (82.96 ± 4.3 vs. 85.36 ± 3.75; p = 0.000) was observed. In addition, the mean muscle mass reduced postoperatively compared to the preoperative mass (2.64 ± 3.82 vs. 8.52 ± 3.73 mm; p = 0.000). Based on the Catterall classification, 56% of children showed good outcomes, and 36% showed fair outcomes. Regarding complications, 20% had postoperative infections. Conclusions In our study, open-wedge varus derotation osteotomy showed improved clinical and radiological outcomes in children with late presentation of LCD disease.