RARE DISEASE
Legg-Calvé-Perthes disease
Legg-Calvé-Perthes disease
Legg-Calvé-Perthes disease
Synonyms: Aseptic necrosis of the capital femoral epiphysis, Osteochondrosis of the capital femoral epiphysis, Perthes disease
Synonyms: Aseptic necrosis of the capital femoral epiphysis, Osteochondrosis of the capital femoral epiphysis, Perthes disease
Synonyms: Aseptic necrosis of the capital femoral epiphysis, Osteochondrosis of the capital femoral epiphysis, Perthes disease
Drug discovery
2
drugs
With orphan designations
Overview
Legg-Calvé-Perthes disease is a juvenile osteonecrosis of the femoral head caused by transient vascular disruption, leading to bone collapse and remodeling. It typically affects children aged 4–12 years (peak 5–7), with a 4:1 male predominance. Bilateral involvement occurs in 10–24% of cases. Prognosis depends on age of onset, femoral head containment, and preservation of hip mobility. Long-term sequelae include early osteoarthritis in 50% of patients with significant femoral head deformity [1][5][10].
Burden
50% require total hip replacement by age 50–60 if femoral head deformity persists [10][11]
Early osteoarthritis risk correlates with residual asphericity (HR=12.4 for severe deformity) [7][16]
Socioeconomic impact: Higher hospitalization rates in deprived populations (incidence up to 33.6/100,000) [6][8]
Therapies
Non-surgical: NSAIDs, activity restriction (crutches/wheelchair), bracing (Petrie cast), and physical therapy for hip mobility <6 years [1][3][14]
Surgical: Femoral/acetabular osteotomies for containment in older children (>8 years) or lateral pillar B/C involvement [1][11][14]
Prognostic tools: Herring classification guides intervention timing; <6 years generally favorable outcomes [12][14]
Categories: rare bone diseases, rare genetic diseases, rare systemic and rheumatological diseases
Research Papers
916 drug discovery papers about Legg-Calvé-Perthes disease, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
916 drug discovery papers about Legg-Calvé-Perthes disease, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
proteins
2026-04-01 | Children’s orthopaedics
The April 2026 Children’s orthopaedics Roundup 360 looks at: Time to stop fixing medial epicondyle fractures; Single-event multilevel surgery for children with cerebral palsy; Is it time to include knee surveillance alongside hip screening for children with cerebral palsy?; Impact of spinal deformity and surgery on health-related quality of life in cerebral palsy: a multicentre prospective controlled trial; What is the need for ongoing hip surveillance for children with ambulatory cerebral palsy after triradiate closure?; Selective growth modulation to improve femoral head shape in severe Perthes’ disease; The long-term outcome from conservative management of femoral anteversion; Normalization of subchondral bone density patterns after surgical treatment for capitellar osteochondritis dissecans.
2025-09-10 | Effects of Growth Hormone Therapy in Children With Growth Hormone Deficiency and Legg-Calvé-Perthes Disease.
Legg-Calvé-Perthes disease (LCPD) is a pediatric hip disorder characterized by idiopathic avascular necrosis of the femoral head. Although its etiology remains unclear, frequent observations of short stature and delayed skeletal maturation have suggested disturbance of systemic growth regulation, particularly involving the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis. This study evaluates the impact of GH deficiency (GHD) and timing of GH therapy (GHT) on radiographic progression and femoral head morphology in LCPD. We conducted a retrospective review of 10 patients (11 hips) with GHD and LCPD treated at a single institution. Patients were stratified into 2 cohorts: group A (n=5), diagnosed with GHD and initiated on GHT before LCPD onset, and group B (n=5, 6 hips), diagnosed and treated during LCPD. Each case was matched 1:2 to controls without GHD based on sex, age at diagnosis, stage, and treatment. Radiographic staging and outcomes were assessed using Waldenström and Stulberg classifications. Growth parameters and treatment-related complications were also recorded. Group A exhibited disease stage duration and femoral head outcomes similar to matched controls. In contrast, group B experienced significantly prolonged fragmentation (1.8 vs. 0.8 y of matched controls, P =0.008) and reossification stages (5.8 vs. 3.9 y, P =0.006), along with worse femoral head sphericity (Stulberg I/II in 0% vs. 67%, P =0.013). Notably, all group B patients had growth deceleration (growth velocity <5 cm/y) before GHD diagnosis. GHT was well tolerated in all cases, with no orthopaedic complications. GHD diagnosed and treated during LCPD was associated with prolonged fragmentation and reossification stages and poorer femoral head morphology. In contrast, patients with GHD treated before LCPD onset demonstrated outcomes similar to matched controls. These findings underscore the potential relevance of the GH/IGF-1 axis in LCPD. Orthopaedic clinicians should maintain vigilance for endocrinopathies in LCPD patients with growth deceleration (growth velocity <5 cm/y) and delayed bone age, as early endocrine referral and treatment may improve outcomes. Level III.
2024-02-12 | Like a Lizard: Repair of Perthes Disease Occurs Through Recapitulation of Development of the Proximal Femoral Epiphysis.
Introduction: Legg-Calve-Perthes Disease (LCPD) is a complex condition with limited understanding about its healing process. The healing mechanism of LCPD is believed to differ significantly from adult hip avascular necrosis (AVN), thus necessitating an exploration into alternative mechanisms. Our research focused on understanding these mechanisms using a review of histologic specimens, a thorough literature review, and translational basic science studies. Methods: Histologic Review: IRB-approved biopsies from five Stage 2 LCPD cases undergoing hinged abduction were analyzed to confirm the presence of cartilage in areas of fragmentation. Literature Search: A comprehensive literature review was performed, scrutinizing publications on the role of cartilage during Stage 2 of LCPD from Perthes' original observations to subsequent studies. Mouse Model: A mouse hip model, chosen for its resemblance to Stage 2 LCPD, was used to study chondrocyte-derived VEGF's role in angiogenesis and ossification. VEGF blockade was employed to confirm its function. Results: Histologic Review: All five biopsies of Stage 2 LCPD cases showed robust cartilage presence in areas of fragmentation (Figure 1). Histological analysis confirmed cartilage leading to new bone formation areas, akin to the physis' zone of ossification. Literature Search: Our literature review identified consistent documentation of cartilage presence during Stage 2 of LCPD in past studies dating back to Perthes, but the role of this cartilage in the healing process was previously not clearly defined. Mouse Model: Chondrocytes were observed to produce a significant amount of VEGF right before vascularization of the hip. Blockade of VEGF production halted both vascularization and ossification. These findings point towards a role for chondrocyte-derived VEGF in promoting angiogenesis and ossification of the femoral head. Conclusion: These findings support the theory that chondrification during Stage 2 of LCPD is part of the unique reparative process of LCPD. The production of VEGF by chondrocytes appears to be integral for vascularization and ossification of the femoral head. We propose that the healing mechanism of LCPD is not a superior form of creeping substitution, but rather an endochondral mediated mechanism of vascularization and ossification, much like a lizard regrowing its tail. Significance: These findings clarify the healing process of LCPD and can inform future treatment protocols. Treatment protocols should consider these biological processes to optimize outcomes in LCPD. Further studies are required to fully elucidate this process and its implications on the management of LCPD. Specifically, it emphasizes the importance of supporting chondrification and the production of VEGF rather than focusing solely on anti-resorptive and osteogenics.
2024-02-07 | Legg-Calvé-Perthes Disease: Diagnosis, Decision Making, and Outcome.
Legg-Calvé-Perthes disease (LCPD), or idiopathic avascular necrosis of the proximal capital femoral epiphysis in children, has a variable presentation and can result in significant femoral head deformity that can lead to long-term functional deficits. Plain radiographic imaging is crucial in diagnosing LCPD and guiding treatment. Although the etiology of LCPD remains unknown, the evolution of the disease has been well characterized to include the phases of ischemia, revascularization, and reossification. The mechanical weakening during these phases of healing place the femoral head at high risk of deformity. Treatment of LCPD, therefore, focuses on minimizing deformity through operative and nonoperative strategies to reduce the risk of premature osteoarthritis. Advanced imaging using perfusion MRI may refine surgical decision making in the future, and biological treatments to improve femoral head healing are on the horizon.
2023-03-07 | Rspo1 inhibited apoptosis of glucocorticoid-induced osteoblasts via Wnt/β-catenin pathway in Legg–Calve–Perthes disease
The pathogenesis of Legg-Calve-Perthes disease (LCPD), a juvenile form of avascular necrosis of the femoral head (ANFH), is not fully understood.The purpose of this work was to study the regulatory effect of R-spondin 1 (Rspo1) on osteoblastic apoptosis and evaluate the pre-clinical efficacy of recombinant human protein Rspo1 (rhRspo1) in treatment of LCPD.This is an experimental study. In vivo rabbit ANFH model was established. Human osteoblast cell line hFOB1.19 (hFOB) was used to overexpress and silence Rspo1 in vitro. Additionally, hFOB cells were induced with glucocorticoid (GC) and methylprednisolone (MP), and treated with rhRspo1. The expressions of Rspo1, β-catenin, Dkk-1, Bcl-2, and caspase-3, and the apoptosis rate of hFOB cells were examined.The expressions of Rspo1 and β-catenin were lower in ANFH rabbits. The expression of Rspo1 was decreased in GC-induced hFOB cells. Compared to the control group, after 1 μM MP induction for 72 h, the expressions of β-catenin and Bcl-2 were higher, while Dkk-1, caspase-3 and cleaved caspase-3 expressions were lower in Rspo1 overexpression and rhRspo1-treated groups. The apoptosis rate of GC-induced hFOB cells was decreased in Rspo1 overexpression and rhRspo1-treated groups compared to the control group.R-spondin 1 inhibited GC-induced osteoblast apoptosis via Wnt/β-catenin pathway, which might be associated with the development of ANFH. Moreover, rhRspo1 had a potential pre-clinical therapeutic effect on LCPD.
cell therapies
2026-06-01 | The Role of Hip Arthrodiastasis in Management of Late-Onset Legg-Calvé-Perthes Disease: A Prospective Case Series.
Late-onset Legg-Calvé-Perthes disease (LCPD), defined as onset after the age of 8 years or younger, is associated with a poor prognosis and limited remodeling potential. The role of hip arthrodiastasis in this age group remains controversial. This prospective case series enrolled patients consecutively and collected data at predefined follow-up intervals. It included 24 patients with late-onset LCPD treated with articulated hip arthrodiastasis using a hinged Ilizarov external fixator combined with percutaneous adductor tenotomy. This reflects a deliberate institutional shift in treatment strategy rather than selective case allocation, which may reduce selection bias but limits the availability of a contemporary control group. All patients were older than 8 years at disease onset and classified as Herring lateral pillar B or C. Clinical outcomes were assessed using the Harris Hip Score (HHS) and range of motion (ROM). Radiographic evaluation included the Sharp acetabular angle, Reimer uncoverage index, epiphyseal index, and modified Stulberg classification at final follow-up. The mean follow-up was 24 months (range: 18 to 30). The mean HHS improved significantly from 47.2 preoperatively to 86.7 at final follow-up (P<0.001). Significant improvements were observed in hip flexion, abduction, and internal rotation (all P<0.001). Radiographically, mean femoral head uncoverage improved from 33.3% to 25.0% (P<0.001), and the Sharp acetabular angle decreased from 42.3 to 37.6 degrees (P<0.001). According to the modified Stulberg classification, 19 hips (79%) had good outcomes (Stulberg II to III), while 5 hips (21%) had poor outcomes (Stulberg IV to V). Complications included pin-tract infections managed with local care and oral antibiotics, as well as a small number of patients requiring additional secondary procedures. Articulated hip arthrodiastasis with adductor tenotomy resulted in favorable short-term clinical and radiographic outcomes in most patients with late-onset LCPD. This technique improved hip motion and radiographic parameters suggestive of improved femoral head containment, without the need for femoral or pelvic osteotomy, and may represent a useful treatment option in this challenging patient population. Level IV-therapeutic case series.
2025-11-17 | Platelet-rich plasma application for the management of early-stage Canine Legg-calvé-perthes disease: A clinical case report.
Legg-Calvé-Perthes disease (LCPD) is characterized by ischemic necrosis of the femoral head, primarily affecting small-breed dogs. An 11-month-old female toy poodle presented with hindlimb lameness due to LCPD. The dog was treated with intra-articular injection of platelet-rich plasma (PRP), and clinical improvement was evaluated using lameness scoring, range of motion, thigh girth measurements, and radiographic assessment. PRP administration resulted in significant clinical improvement, including reduction in lameness, minimal requirement of pain relief, cessation of bone lysis, and increased muscle mass by day 44 post-treatment.
2025-04-10 | LOCAL INJECTION OF HUMAN DENTAL PULP STEM CELLS FOR TREATMENT OF JUVENILE AVASCULAR NECROSIS OF THE FEMORAL HEAD: PRELIMINARY RESULTS IN IMMATURE PIGS.
Legg-Calvé-Perthes disease is a major cause of hip joint deformities in children. Currently, experimental research is directed at investigating biological therapies, including the use of human dental pulp stem cells (hDPSC), which have not yet been studied for this purpose in swine models. This study aimed to evaluate whether local injection of hDPSC induces bone mineralization in the proximal femoral epiphysis in an experimental model of avascular necrosis of the femoral head in immature pigs. Ten immature pigs underwent surgery to induce osteonecrosis of the proximal femoral epiphysis on the right side. In the intervention group (IG), hDPSC injections were performed immediately after osteonecrosis induction, and in the control group (CG), no additional procedure was performed. Left hips were used as controls. After 8 weeks, all animals were euthanized, and macroscopic, radiographic, and histological evaluations were performed. Bone mineralization was greater in the right hips of the IG compared to the CG (p = 0.0356), with an average mineralization index increase of 77.78% after hDPSC injection. Radiographic evaluation of the epiphyseal index showed a greater collapse in the right IG hips compared to the right CG hips (p < 0.001) and macroscopic evaluation showed a higher chance of the femoral head being flat (p = 0,049). The injection of hDPSC into the proximal femoral epiphysis with induced osteonecrosis increases bone mineralization in immature pigs, but these treated hips show more deformity compared to the untreated hips. Level of Evidence IV, Case Series .
2025-03-01 | FP5.7 Clinical Outcomes following Osteochondral Allograft Transplantation of the Femoral Head via Surgical Hip Dislocation
Abstract Background: Treatment of isolated osteochondral loss of the femoral head in young, active patients presents a clinical challenge for orthopedic surgeons. Non-operative management is often associated with poor patient satisfaction and may lead to rapid development of osteoarthritis. Additionally, hip arthroplasty in young patients are associated with concerns regarding implant longevity. The purpose of this study was to evaluate clinical and patient reported outcome measures (PROMs) following osteochondral allograft (OCA) transplantation via surgical hip dislocation (SHD) for isolated cartilage lesions of the femoral head in young patients. Methods: All patients in our institution’s hip preservation group who underwent OCA of the femoral head via SHD between August 2010 and June 2023 were retrospectively reviewed. Demographic and perioperative data were collected and need for subsequent surgery was recorded at most recent follow-up. Modified Harris Hip Score (mHHS) and International Hip Outcome Tool 12 (iHOT-12) were collected pre-operatively and post-operatively. Minimal clinically important difference (MCID) thresholds for hip arthroscopy were used to assess patient outcomes. Results: Twenty-nine patients (51.7% female; mean age 21.6 years) were included. Pre-operative diagnoses included developmental dysplasia (n=9, 31.0%), post-traumatic (n=9, 31.0%), femoroacetabular impingement (n=5, 17.2%), Legg-Calvé-Perthes disease (n=3, 10.3%), avascular necrosis (n=2, 6.9%), and chondroblastoma (n=1, 3.5%). Mean lesion size was mm 418 (range: 154-972 mm) and mean OCA graft depth was 8.5 mm (range: 6-16 mm). Fourteen patients (48.3%) had a history of prior ipsilateral hip surgery. At a mean 41.5-month (range: 5.8–126.0 month) follow-up, mHHS improved from 58.5 to 84.1 (p<.001), and iHOT-12 improved from 34.7 to 77.9 (p<.001). MCID was achieved in 84% of patients for both mHHS and iHOT-12. Four patients (13.7%) required conversion to hip arthroplasty (3 total hip arthroplasties, 1 hip resurfacing) at an average of 2.5 years following OCA via SHD. Conclusions: Treatment of osteochondral lesions with OCA via SHD was associated with significant post-operative improvements in PROMs, and the rate of conversion to hip arthroplasty at average follow up of nearly 4 years was relatively low in our cohort. Osteochondral allograft transplantation may provide a safe, versatile surgical option for treating isolated femoral head chondral lesions in young patients.
2024-06-03 | Effects of bone marrow-derived mesenchymal stem cell transplantation in piglet Legg-Calve-Perthes disease models: a pilot study.
This preliminary study investigated the efficacy and safety of bone marrow-derived mesenchymal stem cell transplantation in a piglet Legg-Calve-Perthes disease (LCPD) model. The LCPD model was induced in two Landrace piglets (6- and 7-week-old, weighing 12 and 17 kg, respectively) by ligaturing the femoral neck. In the first piglet, the natural LCPD course was observed. In the second piglet, 4 weeks after ligaturing the femoral neck, simple medium and medium containing 2.44 × 10 7 bone marrow-derived mesenchymal stem cells were transplanted into the right and left femoral heads after core decompression, respectively. Plain radiographs were obtained every 4 weeks, and the epiphyseal quotient was calculated by dividing the maximum epiphysis height by the maximum epiphysis diameter. The piglets were sacrificed at 14 weeks postoperatively. The femoral heads were extracted and evaluated grossly, pathologically, and by using computed tomography. The transplanted cell characteristics were evaluated using flow cytometry. Flattening of the epiphysis was observed in both femoral heads of the first piglet and only in the right hip of the second piglet. The epiphyseal quotients immediately and at 14 weeks postoperatively in the right femoral head of the second piglet were 0.40 and 0.14, respectively, while those of the left femoral head were 0.30 and 0.42, respectively. Hematoxylin and eosin staining did not reveal physeal bar or tumor cell formation. The transplanted cells were 99.2%, 65.9%, 18.2%, and 0.16% positive for CD44, CD105, CD29, and CD31, respectively. Core decompression combined with bone marrow-derived mesenchymal stem cell transplantation prevented epiphyseal collapse.
small molecules
2026-09-08 | Patient-Derived iPSC-MSC Modelling Reveals Reversible GSK3-Mediated Suppression of Mesenchymal Lineage Differentiation in Legg-Calvé-Perthes Disease.
Legg-Calvé-Perthes disease (LCPD) is an idiopathic paediatric osteonecrosis characterized by avascular injury to the femoral head, resulting in structural collapse and early osteoarthritis. Although mesenchymal stem cell (MSC) dysfunction has been implicated, the underlying mechanisms remain unclear due to the absence of human disease models. Here, we generated patient-specific induced pluripotent stem cells (iPSCs) from dermal fibroblasts of LCPD patients and differentiated them into mesenchymal stem cells (iMSCs) to establish an in vitro platform for mechanistic interrogation. LCPD-iMSCs exhibited hallmark disease-associated phenotypes, including concurrent suppression of osteogenic, adipogenic and chondrogenic differentiation, accompanied by enhanced phosphorylation of GSK3α/β, reduced β-catenin abundance and attenuated canonical Wnt signalling. Transcriptomic analyses revealed alterations in extracellular matrix organization, adhesion pathways and PI3K-Akt/MAPK signalling, consistent with a cellular environment predisposed to impaired mesenchymal function. Pharmacological inhibition of GSK3 using lithium chloride restored β-catenin levels, improved osteogenic and adipogenic marker expression, and enhanced matrix deposition, demonstrating functional reversibility of the LCPD phenotype. These findings identify GSK3-mediated β-catenin destabilization as a central regulator of MSC lineage impairment in LCPD and establish a patient-derived iPSC-MSC model as a valuable platform for mechanistic and therapeutic exploration in paediatric osteonecrosis.
2026-05-20 | IL-6-induced endothelial microparticles exacerbate juvenile ischemic osteonecrosis by promoting Osteoclastogenesis: Implications for Perthes disease.
Perthes disease is a debilitating idiopathic osteonecrosis of the pediatric femoral head and is characterized by femoral head deformity driven by uncoupled bone remodelling, with excessive osteoclastic activity. However, the systemic signals orchestrating this localized bone destruction remain poorly understood. In this study, we found that circulating microparticles (MPs) isolated from the plasma of patients with Perthes disease at the necrotic stage exhibited a greater capacity to promote osteoclast differentiation than MPs from healthy controls. Given the elevated interleukin-6 (IL-6) levels observed in these patients, we characterized endothelial microparticles (EMPs) generated from human umbilical vein endothelial cells (HUVECs) stimulated with IL-6 (IL-6-induced EMPs). Functionally, IL-6-induced EMPs markedly enhanced monocyte-endothelial adhesion, were actively internalized by bone marrow-derived macrophages (BMMs), and potentiated RANKL-induced osteoclastogenesis. In vivo, using a juvenile ischemic osteonecrosis (JIO) model, fluorescence tracking revealed that systemically administered EMPs accumulated in the skeletal tissue, with preferential localization to the ischemic epiphysis. Furthermore, administration of IL-6-induced EMPs exacerbated epiphyseal deformity and trabecular deterioration, accompanied by increased TRAP-positive osteoclast accumulation at the necrotic site. Collectively, these findings elucidate a pathogenic cellular signaling axis wherein inflammation-induced endothelial vesicles act as systemic messengers to trigger localized bone destruction, highlighting the IL-6-EMPs-osteoclast axis as a potential therapeutic target.
2026-05-14 | TOTAL HIP ARTHROPLASTY IN LEGG-CALVÉ-PERTHES DISEASE: A STUDY FROM THE AUSTRALIAN ORTHOPAEDIC ASSOCIATION NATIONAL JOINT REPLACEMENT REGISTRY
Background Legg-Calve-Perthes disease (LCPD) is a paediatric hip disorder characterised by idiopathic ischaemic necrosis and early osteoarthritis. There is limited evidence on revision outcomes for total hip arthroplasty (THA) in LCPD compared to primary osteoarthritis (OA). Methods Data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) was analysed to determine cumulative percent revision rate (CPR), revision indication and functional outcome scores for THA performed for patients undergoing THA for Perthes disease and primary OA between 2003 and 2023. Results There were 1159 THAs for LCPD and 521,603 for primary OA available for analysis. Patients with LCPD incurred a higher CPR in the first two weeks postoperatively, but no difference was observed beyond this time. The CPR adjusted for age, head size, sex and femoral fixation for patients with LCPD at 18 years was 8.5% (95% CI 5.6,12.8) compared to 7.1% (95% CI 7.0, 7.3) for patients with primary OA. There was no difference in the reason for revision. Functional outcome scores were similar, although those patients with LCPD had slightly lower improvement in the Oxford Hip Score. Conclusion Revision rates following THA are comparable between patients with LCPD and primary OA at eighteen years post-operatively. The higher early revision rate in LCPD patients warrants further investigation into contributing factors including surgical planning, types of prostheses, and the influence of previous surgery.
2026-02-13 | Avascular Necrosis of Femoral Head in Dogs
Avascular necrosis (AVN) of the femoral head, also known as Legg-Calvé- Perthes disease (LCPD), is a debilitating orthopedic condition primarily affecting young, small to toy breed dogs. This disease is characterised by the death of bone tissue in the femoral head due to an interruption of its blood supply. The lack of blood flow leads to the collapse of the femoral head and subsequent degenerative changes in the coxofemoral joint, resulting in pain and lameness.
2026-02-12 | Is congenital thrombotic thrombocytopenic purpura a risk factor for ischemic osteonecrosis of the hip joint (Legg-Calvé-Perthes disease)?
Weise et al. reported on a 41-year-old patient previously diagnosed with congenital thrombotic thrombocytopenic purpura undergoing total hip replacement surgery for Perthes disease. This case raises the question whether ischemic osteonecrosis of the femoral head is another so far underrecognized comorbidity causally linked to congenital thrombotic thrombocytopenic purpura.
antibodies
2025-09-22 | Cytokine profile of synovial fluid children with Legg-Calve-Perthes disease and transient synovitis of the hip
Background. The nature of synovitis development in the early stages of Legg-Calve-Perthes disease (LCPD), some issues of the pathogenesis of further osteodestructive processes remain not fully known. At the same time, a targeted treatment option for hip osteochondropathy should be based on a complete understanding of the dysregulation of osteogenesis at the molecular and cellular level. Thus, knowledge about the patterns of changes in the molecular composition of synovial fluid during the induction of osteodestruction in the case of LCPD can serve as the basis for the introduction of new diagnostic criteria for this pathology and strategies for its treatment, including the use of genetically engineered drugs. Aim. To perform a comparative analysis of the concentration of immunoregulatory molecules in synovial fluid in patients with Legg-Calve-Perthes disease in relation to transient hip synovitis. Materials and methods. The concentration of five mediators/chemokines/cytokines (CD40, MDC/CCL22, Fractalkin (CX3CL1), IP10/CXCL10, VEGF) in synovial fluid was analyzed in 42 children diagnosed with transient synovitis of the hip (TS), as well as in 26 patients diagnosed with stage 2 BLCP disease, according to the Waldenström classification. Results. The performed study indicates the different nature and nature of synovial inflammation with favorably occurring TS and LCPВ. The concentration of regulatory molecules in synovial fluid depends on the leading etiological factor and can influence the processes of osteoresorption and osteogenesis. Thus, changes in cytokine activity in patients with BLCP indicate the importance of disorders in the coupling of angiogenesis and osteogenesis at the molecular and cellular level. An increase in the concentration of phosphoprotein CD40 against the background of the induction of VEGF glucoprotein proliferation is associated with the activation of inflammation in vascular disorders. At the same time, with the development of TS, there was an increase in the level of cytokine IP10, which regulates the Th1 immune response. Conclusions. In TS, the leading factor is the immune-inflammatory response with activation of the chemokine system. The manifestation of inflammation in LCPD is associated with disturbances in the coupling system of angiogenesis and osteogenesis at the molecular and cellular level, and increased expression of inflammatory mediators.
2023-12-19 | Identifying the causal relationship between immune factors and osteonecrosis: A Two-Sample Mendelian Randomization Study
Backgrounds: A wealth of evidence intimates a profound connection between the immune system and osteonecrosis, albeit the specific immune factors underlying this connection remain largely veiled. Methods A bidirectional Mendelian randomization (MR) study was conducted based on genome-wide association study (GWAS) summary data to identify causal links between 731 immune factors and osteonecrosis including drug-induced osteonecrosis. Preliminary MR analysis was accomplished utilizing the inverse-variance weighted method (IVW) under a multiplicative random effects model, and heterogeneity and potential horizontal pleiotropy were evaluated through Cochrane's Q-test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis. Results Upon false discovery rate correction, the gene-predicted level of one immune factor (CD62L- monocyte %monocyte) exhibited a significant positive correlation with osteonecrosis, while eight immune traits associated with monocytes, dendritic cells, and NK cells demonstrated significant causal effects with drug-induced osteonecrosis. Reverse MR revealed no significant correlations. Conclusion This MR research provides genetic evidence for the causal associations between a broad spectrum of immune factors and osteonecrosis. Such a study aids in unraveling the intricate interaction patterns between the immune and skeletal systems, elucidating the pathogenesis of osteonecrosis, and identifying potential novel therapeutic approaches.
2021-08-09 | Anti-Interleukin-6 Therapy Decreases Hip Synovitis and Bone Resorption and Increases Bone Formation Following Ischemic Osteonecrosis of the Femoral Head.
Legg-Calvé-Perthes disease (LCPD) is a juvenile form of ischemic femoral head osteonecrosis, which produces chronic hip synovitis, permanent femoral head deformity, and premature osteoarthritis. Currently, there is no medical therapy for LCPD. Interleukin-6 (IL-6) is significantly elevated in the synovial fluid of patients with LCPD. We hypothesize that IL-6 elevation promotes chronic hip synovitis and impairs bone healing after ischemic osteonecrosis. We set out to test if anti-IL-6 therapy using tocilizumab can decrease hip synovitis and improve bone healing in the piglet model of LCPD. Fourteen piglets were surgically induced with ischemic osteonecrosis and assigned to two groups: the no treatment group (n = 7) and the tocilizumab group (15 to 20 mg/kg, biweekly intravenous injection, n = 7). All animals were euthanized 8 weeks after the induction of osteonecrosis. Hip synovium and femoral heads were assessed for hip synovitis and bone healing using histology, micro-CT, and histomorphometry. The mean hip synovitis score and the number of synovial macrophages and vessels were significantly lower in the tocilizumab group compared with the no treatment group (p < .0001, p = .01, and p < .01, respectively). Micro-CT analysis of the femoral heads showed a significantly higher bone volume in the tocilizumab group compared with the no treatment group (p = .02). The histologic assessment revealed a significantly lower number of osteoclasts per bone surface (p < .001) in the tocilizumab group compared with the no treatment group. Moreover, fluorochrome labeling showed a significantly higher percent of mineralizing bone surface (p < .01), bone formation rate per bone surface (p < .01), and mineral apposition rate (p = .04) in the tocilizumab group. Taken together, tocilizumab therapy decreased hip synovitis and osteoclastic bone resorption and increased new bone formation after ischemic osteonecrosis. This study provides preclinical evidence that tocilizumab decreases synovitis and improves bone healing in a large animal model of LCPD. © 2020 American Society for Bone and Mineral Research (ASBMR).
2018-08-17 | Interleukin-6 deletion stimulates revascularization and new bone formation following ischemic osteonecrosis in a murine model
Legg-Calvé-Perthes disease (LCPD) is a childhood form of ischemic osteonecrosis of the femoral head which can produce a permanent femoral head deformity and early osteoarthritis. The femoral head deformity results from increased bone resorption and decreased bone formation during repair and remodeling of the necrotic femoral head. A recent study showed that a pro-inflammatory cytokine, interleukin-6 (IL-6), is significantly elevated in the synovial fluid of patients with LCPD. We hypothesized that IL-6 elevation decreases bone formation during the repair process following ischemic osteonecrosis and that IL-6 depletion will increase new bone formation. To test this hypothesis, we surgically induced ischemic osteonecrosis in the wild-type (n = 29) and IL-6 knockout (KO) mice (n = 25). The animals were assessed at 48 h, 2 weeks and 4 weeks following the induction of ischemic osteonecrosis using histologic, histomorphometric and micro-CT methods. IL-6 immunohistochemistry showed high expression of IL-6 in the osteonecrotic side of the wild-type mice at 48 h and 4 weeks following ischemic osteonecrosis, but not in the IL-6 KO mice. We also confirmed an undetectable level of IL-6 expression in the primary osteoblasts of the IL-6 KO mice compared to the readily detectable level in the wild-type mice. Furthermore, we confirmed that IL-6 deletion did not affect the extent of bone necrosis in the IL-6 KO mice compared to the wild-type mice by performing histologic and terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) assessments at 2 weeks following the induction of ischemia. Both groups had the same extent of ischemic osteonecrosis and absence of repair at 2 weeks. At 4 weeks, the necrotic epiphyses showed a significant increase in the extent of revascularization in the IL-6 KO mice compared to the wild-type mice (p = 0.001). In addition, a significantly greater recovery of the hematopoietic bone marrow was observed in the osteonecrotic side of the IL-6 KO mice compared to the wild-type mice (p < 0.01). Vascular endothelial growth factor (VEGF) immunohistochemistry showed regionally increased staining in the areas of repair in the osteonecrosis side of IL-6 KO mice compared to the wild-type mice at 4 weeks following ischemic osteonecrosis. Micro-CT assessment of the wild-type mice at 4 weeks showed a significant decrease in the percent bone volume (p < 0.01) in the osteonecrotic side compared to the control side. In contrast, IL-6 KO mice showed significantly increased bone volume in the osteonecrotic side compared to the osteonecrotic side of WT mice (p < 0.001). No significant difference in the bone volume percentage was found between the control side of the wild-type and the IL-6 KO mice. Histomorphometric analysis at 4 weeks revealed increased osteoblast number/bone surface (p < 0.001), bone formation rate (BFR) (p = 0.0001), and mineral apposition rate (MAR) (p < 0.0001) in the osteonecrotic side of the IL-6 KO mice compared to the wild-type mice. The number of osteoclast/bone surface was also increased in the IL-6 KO mice compared to the wild-type mice (p < 0.0001). No significant difference was observed between the control side of the wild-type and IL-6 KO mice with regards to the number of osteoblast or osteoclast/bone surface, BFR, and MAR. We next obtained primary osteoblasts from IL-6 KO mice and showed they expressed a significantly higher level of RANKL/OPG than wild-type mice (p = 0.001) in hypoxia culture condition. Taken together, the findings indicate that IL-6 deletion stimulates revascularization and new bone formation following ischemic osteonecrosis. This study provides new evidence that therapeutic strategies to block IL-6 may be beneficial for bone healing following ischemic osteonecrosis.
2017-03-14 | Denosumab and surgery for the treatment of Perthes’ disease in a 9-year-old boy: favorable course documented by comprehensive imaging— a case report
A boy aged 9 years and 4 months developed a recurrent right-sided limp. His father, a radiologist, prompted a contrast magnetic resonance imaging (MRI) after 6 weeks and diagnosed early Perthes’ di...
other
2023-05-26 | Construction of ceRNA network based on RNA-seq for identifying prognostic lncRNA biomarkers in Perthes disease
Introduction: Legg-Calvé-Perthes disease or Perthes disease is a condition that occurs in children aged 2 to 15 years, and is characterized by osteonecrosis of the femoral head, which results in physical limitations. Despite ongoing research, the pathogenesis and molecular mechanisms underlying the development of Perthes disease remain unclear. In order to obtain further insights, the expression patterns of long non-coding RNAs (lncRNAs), miRNAs, and mRNAs in a rabbit model of Perthes disease were analyzed in this study by transcriptome sequencing. Methods and results: The results of RNA-seq analyses revealed that 77 lncRNAs, 239 miRNAs, and 1027 mRNAs were differentially expressed in the rabbit model. This finding suggested that multiple genetic pathways are involved in the development of Perthes disease. A weighted gene co-expression network analysis (WGCNA) network was subsequently constructed using the differentially expressed mRNAs (DEmRNAs), and network analysis revealed that the genes associated with angiogenesis and platelet activation were downregulated, which was consistent with the findings of Perthes disease. A competing endogenous RNA (ceRNA) network was additionally constructed using 29 differentially expressed lncRNAs (including HIF3A and LOC103350994), 28 differentially expressed miRNAs (including ocu-miR-574-5p and ocu-miR-324-3p), and 76 DEmRNAs (including ALOX12 and PTGER2). Disscusion: The results obtained herein provide novel perspectives regarding the pathogenesis and molecular mechanisms underlying the development of Perthes disease. The findings of this study can pave the way for the development of effective therapeutic strategies for Perthes disease in future.
2019-05-22 | The role and underlying mechanisms of microRNA‑214 in Legg‑Calv�‑Perthes disease
Legg‑Calvé‑Perthes disease (LCPD) is a pediatric form of femoral head osteonecrosis with unknown etiology. MicroRNAs (miRs) have been revealed to serve an important role in LCPD. MiR‑214 serves an important role in chondrogenesis. The aim of the present study was to investigate the potential role of miR‑214 in LCPD and the underlying mechanisms. The expression levels of miR‑214 and B‑cell lymphoma 2 (Bcl‑2)‑associated X protein (Bax) in dexamethasone (DEX)‑treated TC28 cells, and the femoral head cartilage tissues, serum and primary chondrocytes of patients with LCPD, and healthy individuals were determined via reverse transcription quantitative polymerase chain reaction and western blot analysis. A luciferase reporter assay was conducted to investigate the association between miR‑214 and Bax, while cell viability was determined via an MTT assay, and flow cytometry was performed to investigate cell apoptosis. The results revealed that miR‑214 was downregulated and Bax was upregulated in DEX‑treated TC28 cells and tissues obtained from patients with LCPD. MiR‑214 was demonstrated to directly target Bax and negatively regulate its expression. DEX administration significantly suppressed cell proliferation, promoted apoptosis and decreased the Bcl‑2/Bax ratio in TC28 cells; overexpression of miR‑214 induced opposing effects, which were reversed by Bax overexpression. In conclusion, the results indicated that miR‑214 and Bax may be potential therapeutic targets for the future clinical treatment of LCPD.
2017-11-08 | Downregulated SOX9 mediated by miR‑206 promoted cell apoptosis in Legg-Calv�-Perthes disease
Legg-Calvé-Perthes disease (LCPD) commonly onsets in adolescents, and threatens their health. However, the potential mechanism underlying LCPD remains unclear. MicroRNA (miR)-206 and SRY-box 9 (SOX9) serve an important role in chondrocytes; however, their role in LCPD remains ambiguous. In the present study, whether miR-206 and SOX9 mediated cell apoptosis in dexamethasone (DEX)-induced LCPD was investigated. The chondrocytes of the LCPD and normal control group were isolated from clinical tissues. Reverse transcription-quantitative polymerase chain reaction was used to evaluate the expression of miR-206 and SOX9 mRNA. Western blotting was used to measure the protein level of SOX9. A combination of Annexin V-fluorescein isothiocyanate flow cytometry was used to assess cell apoptosis. The association between miR-206 and SOX9 was detected using a luciferase reporter assay. miR-206 was overexpressed while SOX9 was downregulated in chondrocytes treated with DEX obtained from patients with LCPD. miR-206 targeted SOX9 to regulate its expression. Overexpression of miR-206 promoted cell apoptosis in TC28, while it was reversed by SOX9 overexpression. TC28 cells pretreated with DEX significantly promoted cell apoptosis, while cells transfected with miR-206 inhibitor significantly reversed the effect; however, downregulated SOX9 abolished the effects of miR-206 inhibitor. SOX9 mediated by miR-206 possibly contributed to the pathogenesis of LCPD. The results of the present study suggest that miR-206 and SOX9 function as important therapeutic targets for the future of clinical therapy.
proteins
2026-04-01 | Children’s orthopaedics
The April 2026 Children’s orthopaedics Roundup 360 looks at: Time to stop fixing medial epicondyle fractures; Single-event multilevel surgery for children with cerebral palsy; Is it time to include knee surveillance alongside hip screening for children with cerebral palsy?; Impact of spinal deformity and surgery on health-related quality of life in cerebral palsy: a multicentre prospective controlled trial; What is the need for ongoing hip surveillance for children with ambulatory cerebral palsy after triradiate closure?; Selective growth modulation to improve femoral head shape in severe Perthes’ disease; The long-term outcome from conservative management of femoral anteversion; Normalization of subchondral bone density patterns after surgical treatment for capitellar osteochondritis dissecans.
2025-09-10 | Effects of Growth Hormone Therapy in Children With Growth Hormone Deficiency and Legg-Calvé-Perthes Disease.
Legg-Calvé-Perthes disease (LCPD) is a pediatric hip disorder characterized by idiopathic avascular necrosis of the femoral head. Although its etiology remains unclear, frequent observations of short stature and delayed skeletal maturation have suggested disturbance of systemic growth regulation, particularly involving the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis. This study evaluates the impact of GH deficiency (GHD) and timing of GH therapy (GHT) on radiographic progression and femoral head morphology in LCPD. We conducted a retrospective review of 10 patients (11 hips) with GHD and LCPD treated at a single institution. Patients were stratified into 2 cohorts: group A (n=5), diagnosed with GHD and initiated on GHT before LCPD onset, and group B (n=5, 6 hips), diagnosed and treated during LCPD. Each case was matched 1:2 to controls without GHD based on sex, age at diagnosis, stage, and treatment. Radiographic staging and outcomes were assessed using Waldenström and Stulberg classifications. Growth parameters and treatment-related complications were also recorded. Group A exhibited disease stage duration and femoral head outcomes similar to matched controls. In contrast, group B experienced significantly prolonged fragmentation (1.8 vs. 0.8 y of matched controls, P =0.008) and reossification stages (5.8 vs. 3.9 y, P =0.006), along with worse femoral head sphericity (Stulberg I/II in 0% vs. 67%, P =0.013). Notably, all group B patients had growth deceleration (growth velocity <5 cm/y) before GHD diagnosis. GHT was well tolerated in all cases, with no orthopaedic complications. GHD diagnosed and treated during LCPD was associated with prolonged fragmentation and reossification stages and poorer femoral head morphology. In contrast, patients with GHD treated before LCPD onset demonstrated outcomes similar to matched controls. These findings underscore the potential relevance of the GH/IGF-1 axis in LCPD. Orthopaedic clinicians should maintain vigilance for endocrinopathies in LCPD patients with growth deceleration (growth velocity <5 cm/y) and delayed bone age, as early endocrine referral and treatment may improve outcomes. Level III.
2024-02-12 | Like a Lizard: Repair of Perthes Disease Occurs Through Recapitulation of Development of the Proximal Femoral Epiphysis.
Introduction: Legg-Calve-Perthes Disease (LCPD) is a complex condition with limited understanding about its healing process. The healing mechanism of LCPD is believed to differ significantly from adult hip avascular necrosis (AVN), thus necessitating an exploration into alternative mechanisms. Our research focused on understanding these mechanisms using a review of histologic specimens, a thorough literature review, and translational basic science studies. Methods: Histologic Review: IRB-approved biopsies from five Stage 2 LCPD cases undergoing hinged abduction were analyzed to confirm the presence of cartilage in areas of fragmentation. Literature Search: A comprehensive literature review was performed, scrutinizing publications on the role of cartilage during Stage 2 of LCPD from Perthes' original observations to subsequent studies. Mouse Model: A mouse hip model, chosen for its resemblance to Stage 2 LCPD, was used to study chondrocyte-derived VEGF's role in angiogenesis and ossification. VEGF blockade was employed to confirm its function. Results: Histologic Review: All five biopsies of Stage 2 LCPD cases showed robust cartilage presence in areas of fragmentation (Figure 1). Histological analysis confirmed cartilage leading to new bone formation areas, akin to the physis' zone of ossification. Literature Search: Our literature review identified consistent documentation of cartilage presence during Stage 2 of LCPD in past studies dating back to Perthes, but the role of this cartilage in the healing process was previously not clearly defined. Mouse Model: Chondrocytes were observed to produce a significant amount of VEGF right before vascularization of the hip. Blockade of VEGF production halted both vascularization and ossification. These findings point towards a role for chondrocyte-derived VEGF in promoting angiogenesis and ossification of the femoral head. Conclusion: These findings support the theory that chondrification during Stage 2 of LCPD is part of the unique reparative process of LCPD. The production of VEGF by chondrocytes appears to be integral for vascularization and ossification of the femoral head. We propose that the healing mechanism of LCPD is not a superior form of creeping substitution, but rather an endochondral mediated mechanism of vascularization and ossification, much like a lizard regrowing its tail. Significance: These findings clarify the healing process of LCPD and can inform future treatment protocols. Treatment protocols should consider these biological processes to optimize outcomes in LCPD. Further studies are required to fully elucidate this process and its implications on the management of LCPD. Specifically, it emphasizes the importance of supporting chondrification and the production of VEGF rather than focusing solely on anti-resorptive and osteogenics.
2024-02-07 | Legg-Calvé-Perthes Disease: Diagnosis, Decision Making, and Outcome.
Legg-Calvé-Perthes disease (LCPD), or idiopathic avascular necrosis of the proximal capital femoral epiphysis in children, has a variable presentation and can result in significant femoral head deformity that can lead to long-term functional deficits. Plain radiographic imaging is crucial in diagnosing LCPD and guiding treatment. Although the etiology of LCPD remains unknown, the evolution of the disease has been well characterized to include the phases of ischemia, revascularization, and reossification. The mechanical weakening during these phases of healing place the femoral head at high risk of deformity. Treatment of LCPD, therefore, focuses on minimizing deformity through operative and nonoperative strategies to reduce the risk of premature osteoarthritis. Advanced imaging using perfusion MRI may refine surgical decision making in the future, and biological treatments to improve femoral head healing are on the horizon.
2023-03-07 | Rspo1 inhibited apoptosis of glucocorticoid-induced osteoblasts via Wnt/β-catenin pathway in Legg–Calve–Perthes disease
The pathogenesis of Legg-Calve-Perthes disease (LCPD), a juvenile form of avascular necrosis of the femoral head (ANFH), is not fully understood.The purpose of this work was to study the regulatory effect of R-spondin 1 (Rspo1) on osteoblastic apoptosis and evaluate the pre-clinical efficacy of recombinant human protein Rspo1 (rhRspo1) in treatment of LCPD.This is an experimental study. In vivo rabbit ANFH model was established. Human osteoblast cell line hFOB1.19 (hFOB) was used to overexpress and silence Rspo1 in vitro. Additionally, hFOB cells were induced with glucocorticoid (GC) and methylprednisolone (MP), and treated with rhRspo1. The expressions of Rspo1, β-catenin, Dkk-1, Bcl-2, and caspase-3, and the apoptosis rate of hFOB cells were examined.The expressions of Rspo1 and β-catenin were lower in ANFH rabbits. The expression of Rspo1 was decreased in GC-induced hFOB cells. Compared to the control group, after 1 μM MP induction for 72 h, the expressions of β-catenin and Bcl-2 were higher, while Dkk-1, caspase-3 and cleaved caspase-3 expressions were lower in Rspo1 overexpression and rhRspo1-treated groups. The apoptosis rate of GC-induced hFOB cells was decreased in Rspo1 overexpression and rhRspo1-treated groups compared to the control group.R-spondin 1 inhibited GC-induced osteoblast apoptosis via Wnt/β-catenin pathway, which might be associated with the development of ANFH. Moreover, rhRspo1 had a potential pre-clinical therapeutic effect on LCPD.
cell therapies
2026-06-01 | The Role of Hip Arthrodiastasis in Management of Late-Onset Legg-Calvé-Perthes Disease: A Prospective Case Series.
Late-onset Legg-Calvé-Perthes disease (LCPD), defined as onset after the age of 8 years or younger, is associated with a poor prognosis and limited remodeling potential. The role of hip arthrodiastasis in this age group remains controversial. This prospective case series enrolled patients consecutively and collected data at predefined follow-up intervals. It included 24 patients with late-onset LCPD treated with articulated hip arthrodiastasis using a hinged Ilizarov external fixator combined with percutaneous adductor tenotomy. This reflects a deliberate institutional shift in treatment strategy rather than selective case allocation, which may reduce selection bias but limits the availability of a contemporary control group. All patients were older than 8 years at disease onset and classified as Herring lateral pillar B or C. Clinical outcomes were assessed using the Harris Hip Score (HHS) and range of motion (ROM). Radiographic evaluation included the Sharp acetabular angle, Reimer uncoverage index, epiphyseal index, and modified Stulberg classification at final follow-up. The mean follow-up was 24 months (range: 18 to 30). The mean HHS improved significantly from 47.2 preoperatively to 86.7 at final follow-up (P<0.001). Significant improvements were observed in hip flexion, abduction, and internal rotation (all P<0.001). Radiographically, mean femoral head uncoverage improved from 33.3% to 25.0% (P<0.001), and the Sharp acetabular angle decreased from 42.3 to 37.6 degrees (P<0.001). According to the modified Stulberg classification, 19 hips (79%) had good outcomes (Stulberg II to III), while 5 hips (21%) had poor outcomes (Stulberg IV to V). Complications included pin-tract infections managed with local care and oral antibiotics, as well as a small number of patients requiring additional secondary procedures. Articulated hip arthrodiastasis with adductor tenotomy resulted in favorable short-term clinical and radiographic outcomes in most patients with late-onset LCPD. This technique improved hip motion and radiographic parameters suggestive of improved femoral head containment, without the need for femoral or pelvic osteotomy, and may represent a useful treatment option in this challenging patient population. Level IV-therapeutic case series.
2025-11-17 | Platelet-rich plasma application for the management of early-stage Canine Legg-calvé-perthes disease: A clinical case report.
Legg-Calvé-Perthes disease (LCPD) is characterized by ischemic necrosis of the femoral head, primarily affecting small-breed dogs. An 11-month-old female toy poodle presented with hindlimb lameness due to LCPD. The dog was treated with intra-articular injection of platelet-rich plasma (PRP), and clinical improvement was evaluated using lameness scoring, range of motion, thigh girth measurements, and radiographic assessment. PRP administration resulted in significant clinical improvement, including reduction in lameness, minimal requirement of pain relief, cessation of bone lysis, and increased muscle mass by day 44 post-treatment.
2025-04-10 | LOCAL INJECTION OF HUMAN DENTAL PULP STEM CELLS FOR TREATMENT OF JUVENILE AVASCULAR NECROSIS OF THE FEMORAL HEAD: PRELIMINARY RESULTS IN IMMATURE PIGS.
Legg-Calvé-Perthes disease is a major cause of hip joint deformities in children. Currently, experimental research is directed at investigating biological therapies, including the use of human dental pulp stem cells (hDPSC), which have not yet been studied for this purpose in swine models. This study aimed to evaluate whether local injection of hDPSC induces bone mineralization in the proximal femoral epiphysis in an experimental model of avascular necrosis of the femoral head in immature pigs. Ten immature pigs underwent surgery to induce osteonecrosis of the proximal femoral epiphysis on the right side. In the intervention group (IG), hDPSC injections were performed immediately after osteonecrosis induction, and in the control group (CG), no additional procedure was performed. Left hips were used as controls. After 8 weeks, all animals were euthanized, and macroscopic, radiographic, and histological evaluations were performed. Bone mineralization was greater in the right hips of the IG compared to the CG (p = 0.0356), with an average mineralization index increase of 77.78% after hDPSC injection. Radiographic evaluation of the epiphyseal index showed a greater collapse in the right IG hips compared to the right CG hips (p < 0.001) and macroscopic evaluation showed a higher chance of the femoral head being flat (p = 0,049). The injection of hDPSC into the proximal femoral epiphysis with induced osteonecrosis increases bone mineralization in immature pigs, but these treated hips show more deformity compared to the untreated hips. Level of Evidence IV, Case Series .
2025-03-01 | FP5.7 Clinical Outcomes following Osteochondral Allograft Transplantation of the Femoral Head via Surgical Hip Dislocation
Abstract Background: Treatment of isolated osteochondral loss of the femoral head in young, active patients presents a clinical challenge for orthopedic surgeons. Non-operative management is often associated with poor patient satisfaction and may lead to rapid development of osteoarthritis. Additionally, hip arthroplasty in young patients are associated with concerns regarding implant longevity. The purpose of this study was to evaluate clinical and patient reported outcome measures (PROMs) following osteochondral allograft (OCA) transplantation via surgical hip dislocation (SHD) for isolated cartilage lesions of the femoral head in young patients. Methods: All patients in our institution’s hip preservation group who underwent OCA of the femoral head via SHD between August 2010 and June 2023 were retrospectively reviewed. Demographic and perioperative data were collected and need for subsequent surgery was recorded at most recent follow-up. Modified Harris Hip Score (mHHS) and International Hip Outcome Tool 12 (iHOT-12) were collected pre-operatively and post-operatively. Minimal clinically important difference (MCID) thresholds for hip arthroscopy were used to assess patient outcomes. Results: Twenty-nine patients (51.7% female; mean age 21.6 years) were included. Pre-operative diagnoses included developmental dysplasia (n=9, 31.0%), post-traumatic (n=9, 31.0%), femoroacetabular impingement (n=5, 17.2%), Legg-Calvé-Perthes disease (n=3, 10.3%), avascular necrosis (n=2, 6.9%), and chondroblastoma (n=1, 3.5%). Mean lesion size was mm 418 (range: 154-972 mm) and mean OCA graft depth was 8.5 mm (range: 6-16 mm). Fourteen patients (48.3%) had a history of prior ipsilateral hip surgery. At a mean 41.5-month (range: 5.8–126.0 month) follow-up, mHHS improved from 58.5 to 84.1 (p<.001), and iHOT-12 improved from 34.7 to 77.9 (p<.001). MCID was achieved in 84% of patients for both mHHS and iHOT-12. Four patients (13.7%) required conversion to hip arthroplasty (3 total hip arthroplasties, 1 hip resurfacing) at an average of 2.5 years following OCA via SHD. Conclusions: Treatment of osteochondral lesions with OCA via SHD was associated with significant post-operative improvements in PROMs, and the rate of conversion to hip arthroplasty at average follow up of nearly 4 years was relatively low in our cohort. Osteochondral allograft transplantation may provide a safe, versatile surgical option for treating isolated femoral head chondral lesions in young patients.
2024-06-03 | Effects of bone marrow-derived mesenchymal stem cell transplantation in piglet Legg-Calve-Perthes disease models: a pilot study.
This preliminary study investigated the efficacy and safety of bone marrow-derived mesenchymal stem cell transplantation in a piglet Legg-Calve-Perthes disease (LCPD) model. The LCPD model was induced in two Landrace piglets (6- and 7-week-old, weighing 12 and 17 kg, respectively) by ligaturing the femoral neck. In the first piglet, the natural LCPD course was observed. In the second piglet, 4 weeks after ligaturing the femoral neck, simple medium and medium containing 2.44 × 10 7 bone marrow-derived mesenchymal stem cells were transplanted into the right and left femoral heads after core decompression, respectively. Plain radiographs were obtained every 4 weeks, and the epiphyseal quotient was calculated by dividing the maximum epiphysis height by the maximum epiphysis diameter. The piglets were sacrificed at 14 weeks postoperatively. The femoral heads were extracted and evaluated grossly, pathologically, and by using computed tomography. The transplanted cell characteristics were evaluated using flow cytometry. Flattening of the epiphysis was observed in both femoral heads of the first piglet and only in the right hip of the second piglet. The epiphyseal quotients immediately and at 14 weeks postoperatively in the right femoral head of the second piglet were 0.40 and 0.14, respectively, while those of the left femoral head were 0.30 and 0.42, respectively. Hematoxylin and eosin staining did not reveal physeal bar or tumor cell formation. The transplanted cells were 99.2%, 65.9%, 18.2%, and 0.16% positive for CD44, CD105, CD29, and CD31, respectively. Core decompression combined with bone marrow-derived mesenchymal stem cell transplantation prevented epiphyseal collapse.
small molecules
2026-09-08 | Patient-Derived iPSC-MSC Modelling Reveals Reversible GSK3-Mediated Suppression of Mesenchymal Lineage Differentiation in Legg-Calvé-Perthes Disease.
Legg-Calvé-Perthes disease (LCPD) is an idiopathic paediatric osteonecrosis characterized by avascular injury to the femoral head, resulting in structural collapse and early osteoarthritis. Although mesenchymal stem cell (MSC) dysfunction has been implicated, the underlying mechanisms remain unclear due to the absence of human disease models. Here, we generated patient-specific induced pluripotent stem cells (iPSCs) from dermal fibroblasts of LCPD patients and differentiated them into mesenchymal stem cells (iMSCs) to establish an in vitro platform for mechanistic interrogation. LCPD-iMSCs exhibited hallmark disease-associated phenotypes, including concurrent suppression of osteogenic, adipogenic and chondrogenic differentiation, accompanied by enhanced phosphorylation of GSK3α/β, reduced β-catenin abundance and attenuated canonical Wnt signalling. Transcriptomic analyses revealed alterations in extracellular matrix organization, adhesion pathways and PI3K-Akt/MAPK signalling, consistent with a cellular environment predisposed to impaired mesenchymal function. Pharmacological inhibition of GSK3 using lithium chloride restored β-catenin levels, improved osteogenic and adipogenic marker expression, and enhanced matrix deposition, demonstrating functional reversibility of the LCPD phenotype. These findings identify GSK3-mediated β-catenin destabilization as a central regulator of MSC lineage impairment in LCPD and establish a patient-derived iPSC-MSC model as a valuable platform for mechanistic and therapeutic exploration in paediatric osteonecrosis.
2026-05-20 | IL-6-induced endothelial microparticles exacerbate juvenile ischemic osteonecrosis by promoting Osteoclastogenesis: Implications for Perthes disease.
Perthes disease is a debilitating idiopathic osteonecrosis of the pediatric femoral head and is characterized by femoral head deformity driven by uncoupled bone remodelling, with excessive osteoclastic activity. However, the systemic signals orchestrating this localized bone destruction remain poorly understood. In this study, we found that circulating microparticles (MPs) isolated from the plasma of patients with Perthes disease at the necrotic stage exhibited a greater capacity to promote osteoclast differentiation than MPs from healthy controls. Given the elevated interleukin-6 (IL-6) levels observed in these patients, we characterized endothelial microparticles (EMPs) generated from human umbilical vein endothelial cells (HUVECs) stimulated with IL-6 (IL-6-induced EMPs). Functionally, IL-6-induced EMPs markedly enhanced monocyte-endothelial adhesion, were actively internalized by bone marrow-derived macrophages (BMMs), and potentiated RANKL-induced osteoclastogenesis. In vivo, using a juvenile ischemic osteonecrosis (JIO) model, fluorescence tracking revealed that systemically administered EMPs accumulated in the skeletal tissue, with preferential localization to the ischemic epiphysis. Furthermore, administration of IL-6-induced EMPs exacerbated epiphyseal deformity and trabecular deterioration, accompanied by increased TRAP-positive osteoclast accumulation at the necrotic site. Collectively, these findings elucidate a pathogenic cellular signaling axis wherein inflammation-induced endothelial vesicles act as systemic messengers to trigger localized bone destruction, highlighting the IL-6-EMPs-osteoclast axis as a potential therapeutic target.
2026-05-14 | TOTAL HIP ARTHROPLASTY IN LEGG-CALVÉ-PERTHES DISEASE: A STUDY FROM THE AUSTRALIAN ORTHOPAEDIC ASSOCIATION NATIONAL JOINT REPLACEMENT REGISTRY
Background Legg-Calve-Perthes disease (LCPD) is a paediatric hip disorder characterised by idiopathic ischaemic necrosis and early osteoarthritis. There is limited evidence on revision outcomes for total hip arthroplasty (THA) in LCPD compared to primary osteoarthritis (OA). Methods Data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) was analysed to determine cumulative percent revision rate (CPR), revision indication and functional outcome scores for THA performed for patients undergoing THA for Perthes disease and primary OA between 2003 and 2023. Results There were 1159 THAs for LCPD and 521,603 for primary OA available for analysis. Patients with LCPD incurred a higher CPR in the first two weeks postoperatively, but no difference was observed beyond this time. The CPR adjusted for age, head size, sex and femoral fixation for patients with LCPD at 18 years was 8.5% (95% CI 5.6,12.8) compared to 7.1% (95% CI 7.0, 7.3) for patients with primary OA. There was no difference in the reason for revision. Functional outcome scores were similar, although those patients with LCPD had slightly lower improvement in the Oxford Hip Score. Conclusion Revision rates following THA are comparable between patients with LCPD and primary OA at eighteen years post-operatively. The higher early revision rate in LCPD patients warrants further investigation into contributing factors including surgical planning, types of prostheses, and the influence of previous surgery.
2026-02-13 | Avascular Necrosis of Femoral Head in Dogs
Avascular necrosis (AVN) of the femoral head, also known as Legg-Calvé- Perthes disease (LCPD), is a debilitating orthopedic condition primarily affecting young, small to toy breed dogs. This disease is characterised by the death of bone tissue in the femoral head due to an interruption of its blood supply. The lack of blood flow leads to the collapse of the femoral head and subsequent degenerative changes in the coxofemoral joint, resulting in pain and lameness.
2026-02-12 | Is congenital thrombotic thrombocytopenic purpura a risk factor for ischemic osteonecrosis of the hip joint (Legg-Calvé-Perthes disease)?
Weise et al. reported on a 41-year-old patient previously diagnosed with congenital thrombotic thrombocytopenic purpura undergoing total hip replacement surgery for Perthes disease. This case raises the question whether ischemic osteonecrosis of the femoral head is another so far underrecognized comorbidity causally linked to congenital thrombotic thrombocytopenic purpura.
antibodies
2025-09-22 | Cytokine profile of synovial fluid children with Legg-Calve-Perthes disease and transient synovitis of the hip
Background. The nature of synovitis development in the early stages of Legg-Calve-Perthes disease (LCPD), some issues of the pathogenesis of further osteodestructive processes remain not fully known. At the same time, a targeted treatment option for hip osteochondropathy should be based on a complete understanding of the dysregulation of osteogenesis at the molecular and cellular level. Thus, knowledge about the patterns of changes in the molecular composition of synovial fluid during the induction of osteodestruction in the case of LCPD can serve as the basis for the introduction of new diagnostic criteria for this pathology and strategies for its treatment, including the use of genetically engineered drugs. Aim. To perform a comparative analysis of the concentration of immunoregulatory molecules in synovial fluid in patients with Legg-Calve-Perthes disease in relation to transient hip synovitis. Materials and methods. The concentration of five mediators/chemokines/cytokines (CD40, MDC/CCL22, Fractalkin (CX3CL1), IP10/CXCL10, VEGF) in synovial fluid was analyzed in 42 children diagnosed with transient synovitis of the hip (TS), as well as in 26 patients diagnosed with stage 2 BLCP disease, according to the Waldenström classification. Results. The performed study indicates the different nature and nature of synovial inflammation with favorably occurring TS and LCPВ. The concentration of regulatory molecules in synovial fluid depends on the leading etiological factor and can influence the processes of osteoresorption and osteogenesis. Thus, changes in cytokine activity in patients with BLCP indicate the importance of disorders in the coupling of angiogenesis and osteogenesis at the molecular and cellular level. An increase in the concentration of phosphoprotein CD40 against the background of the induction of VEGF glucoprotein proliferation is associated with the activation of inflammation in vascular disorders. At the same time, with the development of TS, there was an increase in the level of cytokine IP10, which regulates the Th1 immune response. Conclusions. In TS, the leading factor is the immune-inflammatory response with activation of the chemokine system. The manifestation of inflammation in LCPD is associated with disturbances in the coupling system of angiogenesis and osteogenesis at the molecular and cellular level, and increased expression of inflammatory mediators.
2023-12-19 | Identifying the causal relationship between immune factors and osteonecrosis: A Two-Sample Mendelian Randomization Study
Backgrounds: A wealth of evidence intimates a profound connection between the immune system and osteonecrosis, albeit the specific immune factors underlying this connection remain largely veiled. Methods A bidirectional Mendelian randomization (MR) study was conducted based on genome-wide association study (GWAS) summary data to identify causal links between 731 immune factors and osteonecrosis including drug-induced osteonecrosis. Preliminary MR analysis was accomplished utilizing the inverse-variance weighted method (IVW) under a multiplicative random effects model, and heterogeneity and potential horizontal pleiotropy were evaluated through Cochrane's Q-test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis. Results Upon false discovery rate correction, the gene-predicted level of one immune factor (CD62L- monocyte %monocyte) exhibited a significant positive correlation with osteonecrosis, while eight immune traits associated with monocytes, dendritic cells, and NK cells demonstrated significant causal effects with drug-induced osteonecrosis. Reverse MR revealed no significant correlations. Conclusion This MR research provides genetic evidence for the causal associations between a broad spectrum of immune factors and osteonecrosis. Such a study aids in unraveling the intricate interaction patterns between the immune and skeletal systems, elucidating the pathogenesis of osteonecrosis, and identifying potential novel therapeutic approaches.
2021-08-09 | Anti-Interleukin-6 Therapy Decreases Hip Synovitis and Bone Resorption and Increases Bone Formation Following Ischemic Osteonecrosis of the Femoral Head.
Legg-Calvé-Perthes disease (LCPD) is a juvenile form of ischemic femoral head osteonecrosis, which produces chronic hip synovitis, permanent femoral head deformity, and premature osteoarthritis. Currently, there is no medical therapy for LCPD. Interleukin-6 (IL-6) is significantly elevated in the synovial fluid of patients with LCPD. We hypothesize that IL-6 elevation promotes chronic hip synovitis and impairs bone healing after ischemic osteonecrosis. We set out to test if anti-IL-6 therapy using tocilizumab can decrease hip synovitis and improve bone healing in the piglet model of LCPD. Fourteen piglets were surgically induced with ischemic osteonecrosis and assigned to two groups: the no treatment group (n = 7) and the tocilizumab group (15 to 20 mg/kg, biweekly intravenous injection, n = 7). All animals were euthanized 8 weeks after the induction of osteonecrosis. Hip synovium and femoral heads were assessed for hip synovitis and bone healing using histology, micro-CT, and histomorphometry. The mean hip synovitis score and the number of synovial macrophages and vessels were significantly lower in the tocilizumab group compared with the no treatment group (p < .0001, p = .01, and p < .01, respectively). Micro-CT analysis of the femoral heads showed a significantly higher bone volume in the tocilizumab group compared with the no treatment group (p = .02). The histologic assessment revealed a significantly lower number of osteoclasts per bone surface (p < .001) in the tocilizumab group compared with the no treatment group. Moreover, fluorochrome labeling showed a significantly higher percent of mineralizing bone surface (p < .01), bone formation rate per bone surface (p < .01), and mineral apposition rate (p = .04) in the tocilizumab group. Taken together, tocilizumab therapy decreased hip synovitis and osteoclastic bone resorption and increased new bone formation after ischemic osteonecrosis. This study provides preclinical evidence that tocilizumab decreases synovitis and improves bone healing in a large animal model of LCPD. © 2020 American Society for Bone and Mineral Research (ASBMR).
2018-08-17 | Interleukin-6 deletion stimulates revascularization and new bone formation following ischemic osteonecrosis in a murine model
Legg-Calvé-Perthes disease (LCPD) is a childhood form of ischemic osteonecrosis of the femoral head which can produce a permanent femoral head deformity and early osteoarthritis. The femoral head deformity results from increased bone resorption and decreased bone formation during repair and remodeling of the necrotic femoral head. A recent study showed that a pro-inflammatory cytokine, interleukin-6 (IL-6), is significantly elevated in the synovial fluid of patients with LCPD. We hypothesized that IL-6 elevation decreases bone formation during the repair process following ischemic osteonecrosis and that IL-6 depletion will increase new bone formation. To test this hypothesis, we surgically induced ischemic osteonecrosis in the wild-type (n = 29) and IL-6 knockout (KO) mice (n = 25). The animals were assessed at 48 h, 2 weeks and 4 weeks following the induction of ischemic osteonecrosis using histologic, histomorphometric and micro-CT methods. IL-6 immunohistochemistry showed high expression of IL-6 in the osteonecrotic side of the wild-type mice at 48 h and 4 weeks following ischemic osteonecrosis, but not in the IL-6 KO mice. We also confirmed an undetectable level of IL-6 expression in the primary osteoblasts of the IL-6 KO mice compared to the readily detectable level in the wild-type mice. Furthermore, we confirmed that IL-6 deletion did not affect the extent of bone necrosis in the IL-6 KO mice compared to the wild-type mice by performing histologic and terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) assessments at 2 weeks following the induction of ischemia. Both groups had the same extent of ischemic osteonecrosis and absence of repair at 2 weeks. At 4 weeks, the necrotic epiphyses showed a significant increase in the extent of revascularization in the IL-6 KO mice compared to the wild-type mice (p = 0.001). In addition, a significantly greater recovery of the hematopoietic bone marrow was observed in the osteonecrotic side of the IL-6 KO mice compared to the wild-type mice (p < 0.01). Vascular endothelial growth factor (VEGF) immunohistochemistry showed regionally increased staining in the areas of repair in the osteonecrosis side of IL-6 KO mice compared to the wild-type mice at 4 weeks following ischemic osteonecrosis. Micro-CT assessment of the wild-type mice at 4 weeks showed a significant decrease in the percent bone volume (p < 0.01) in the osteonecrotic side compared to the control side. In contrast, IL-6 KO mice showed significantly increased bone volume in the osteonecrotic side compared to the osteonecrotic side of WT mice (p < 0.001). No significant difference in the bone volume percentage was found between the control side of the wild-type and the IL-6 KO mice. Histomorphometric analysis at 4 weeks revealed increased osteoblast number/bone surface (p < 0.001), bone formation rate (BFR) (p = 0.0001), and mineral apposition rate (MAR) (p < 0.0001) in the osteonecrotic side of the IL-6 KO mice compared to the wild-type mice. The number of osteoclast/bone surface was also increased in the IL-6 KO mice compared to the wild-type mice (p < 0.0001). No significant difference was observed between the control side of the wild-type and IL-6 KO mice with regards to the number of osteoblast or osteoclast/bone surface, BFR, and MAR. We next obtained primary osteoblasts from IL-6 KO mice and showed they expressed a significantly higher level of RANKL/OPG than wild-type mice (p = 0.001) in hypoxia culture condition. Taken together, the findings indicate that IL-6 deletion stimulates revascularization and new bone formation following ischemic osteonecrosis. This study provides new evidence that therapeutic strategies to block IL-6 may be beneficial for bone healing following ischemic osteonecrosis.
2017-03-14 | Denosumab and surgery for the treatment of Perthes’ disease in a 9-year-old boy: favorable course documented by comprehensive imaging— a case report
A boy aged 9 years and 4 months developed a recurrent right-sided limp. His father, a radiologist, prompted a contrast magnetic resonance imaging (MRI) after 6 weeks and diagnosed early Perthes’ di...
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2023-05-26 | Construction of ceRNA network based on RNA-seq for identifying prognostic lncRNA biomarkers in Perthes disease
Introduction: Legg-Calvé-Perthes disease or Perthes disease is a condition that occurs in children aged 2 to 15 years, and is characterized by osteonecrosis of the femoral head, which results in physical limitations. Despite ongoing research, the pathogenesis and molecular mechanisms underlying the development of Perthes disease remain unclear. In order to obtain further insights, the expression patterns of long non-coding RNAs (lncRNAs), miRNAs, and mRNAs in a rabbit model of Perthes disease were analyzed in this study by transcriptome sequencing. Methods and results: The results of RNA-seq analyses revealed that 77 lncRNAs, 239 miRNAs, and 1027 mRNAs were differentially expressed in the rabbit model. This finding suggested that multiple genetic pathways are involved in the development of Perthes disease. A weighted gene co-expression network analysis (WGCNA) network was subsequently constructed using the differentially expressed mRNAs (DEmRNAs), and network analysis revealed that the genes associated with angiogenesis and platelet activation were downregulated, which was consistent with the findings of Perthes disease. A competing endogenous RNA (ceRNA) network was additionally constructed using 29 differentially expressed lncRNAs (including HIF3A and LOC103350994), 28 differentially expressed miRNAs (including ocu-miR-574-5p and ocu-miR-324-3p), and 76 DEmRNAs (including ALOX12 and PTGER2). Disscusion: The results obtained herein provide novel perspectives regarding the pathogenesis and molecular mechanisms underlying the development of Perthes disease. The findings of this study can pave the way for the development of effective therapeutic strategies for Perthes disease in future.
2019-05-22 | The role and underlying mechanisms of microRNA‑214 in Legg‑Calv�‑Perthes disease
Legg‑Calvé‑Perthes disease (LCPD) is a pediatric form of femoral head osteonecrosis with unknown etiology. MicroRNAs (miRs) have been revealed to serve an important role in LCPD. MiR‑214 serves an important role in chondrogenesis. The aim of the present study was to investigate the potential role of miR‑214 in LCPD and the underlying mechanisms. The expression levels of miR‑214 and B‑cell lymphoma 2 (Bcl‑2)‑associated X protein (Bax) in dexamethasone (DEX)‑treated TC28 cells, and the femoral head cartilage tissues, serum and primary chondrocytes of patients with LCPD, and healthy individuals were determined via reverse transcription quantitative polymerase chain reaction and western blot analysis. A luciferase reporter assay was conducted to investigate the association between miR‑214 and Bax, while cell viability was determined via an MTT assay, and flow cytometry was performed to investigate cell apoptosis. The results revealed that miR‑214 was downregulated and Bax was upregulated in DEX‑treated TC28 cells and tissues obtained from patients with LCPD. MiR‑214 was demonstrated to directly target Bax and negatively regulate its expression. DEX administration significantly suppressed cell proliferation, promoted apoptosis and decreased the Bcl‑2/Bax ratio in TC28 cells; overexpression of miR‑214 induced opposing effects, which were reversed by Bax overexpression. In conclusion, the results indicated that miR‑214 and Bax may be potential therapeutic targets for the future clinical treatment of LCPD.
2017-11-08 | Downregulated SOX9 mediated by miR‑206 promoted cell apoptosis in Legg-Calv�-Perthes disease
Legg-Calvé-Perthes disease (LCPD) commonly onsets in adolescents, and threatens their health. However, the potential mechanism underlying LCPD remains unclear. MicroRNA (miR)-206 and SRY-box 9 (SOX9) serve an important role in chondrocytes; however, their role in LCPD remains ambiguous. In the present study, whether miR-206 and SOX9 mediated cell apoptosis in dexamethasone (DEX)-induced LCPD was investigated. The chondrocytes of the LCPD and normal control group were isolated from clinical tissues. Reverse transcription-quantitative polymerase chain reaction was used to evaluate the expression of miR-206 and SOX9 mRNA. Western blotting was used to measure the protein level of SOX9. A combination of Annexin V-fluorescein isothiocyanate flow cytometry was used to assess cell apoptosis. The association between miR-206 and SOX9 was detected using a luciferase reporter assay. miR-206 was overexpressed while SOX9 was downregulated in chondrocytes treated with DEX obtained from patients with LCPD. miR-206 targeted SOX9 to regulate its expression. Overexpression of miR-206 promoted cell apoptosis in TC28, while it was reversed by SOX9 overexpression. TC28 cells pretreated with DEX significantly promoted cell apoptosis, while cells transfected with miR-206 inhibitor significantly reversed the effect; however, downregulated SOX9 abolished the effects of miR-206 inhibitor. SOX9 mediated by miR-206 possibly contributed to the pathogenesis of LCPD. The results of the present study suggest that miR-206 and SOX9 function as important therapeutic targets for the future of clinical therapy.
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Drug Discovery Landscape
2 orphan drug designations for Legg-Calvé-Perthes disease.
2 orphan drug designations for Legg-Calvé-Perthes disease.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
clodronate + simvastatin | small molecules | FDA | — | VSI Composites, Inc. |
N-[(2S)-1-[(3aS,6R,6aR)-6-Ethynyl-3-oxohexahydro-2H-furo[3,2-b]pyrrol-4-yl]-4-methyl-1-oxopentan-2-yl]-4-[5-fluoro-2-(4-methylpiperazin-1-yl)-1,3-thiazol-4-yl]benzamide hydrochloride | small molecules | FDA | — | OsteoCat Therapeutics AB |
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