Materiały źródłowe

• #1 Legg-Calve-Perthes Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK513230/

  Legg-Calve-Perthes disease (LCPD) is idiopathic osteonecrosis or idiopathic avascular necrosis of the capital femoral epiphysis of the femoral head. […] The cause of Legg-Calve-Perthes disease is not known. It may be idiopathic or due to other etiology that would disrupt blood flow to the femoral epiphysis, such as trauma (macro or repetitive microtrauma), coagulopathy, and steroid use. Thrombophilia is present in approximately 50% of patients, and some form of coagulopathy is present in up to 75%. […] Typically, Legg-Calve-Perthes disease includes four phases: Necrosis: Disruption of the blood supply leads to infarction of the femoral capital epiphysis, particularly the subchondral cortical bone. Subsequently, this leads to a cessation of the growth of the ossific nucleus. The infarcted bone softens and dies. Fragmentation: The body reabsorbs the infarcted bone. Reossification: Osteoblastic activity takes over, and the femoral epiphysis reestablishes. Remodeling: The new femoral head may be enlarged or flattened. It reshapes during growth. Those that respond to conservative treatment will usually show healing in 2 to 4 years.

• #2 The Pathogenesis and Treatment of Legg-Calvé-Perthes Disease – PubMed

  https://pubmed.ncbi.nlm.nih.gov/27509329/

  Legg-Calv-Perthes disease is a childhood hip condition in which the blood supply to the capital femoral epiphysis is interrupted, causing osteonecrosis and chondronecrosis that lead to progressive deformity of the femoral head and secondary degenerative osteoarthritis in later life. […] The etiology of Legg-Calv-Perthes disease remains unclear, with both biological and mechanical factors playing important roles in the pathogenesis of the condition.

• #3

  https://www.orthobullets.com/pediatrics/4119/legg-calve-perthes-disease

  Legg-Calve-Perthes Disease is an idiopathic avascular necrosis of the proximal femoral epiphysis in children. […] osteonecrosis occurs secondary to disruption of blood supply to femoral head followed by revascularization with subsequent resorption and later collapse. […] creeping substitution provides pathway for remodeling after collapse. […] possible association with abnormal clotting factors (Protein S and Protein C deficiencies) is a controversial etiology. […] thrombophilia has been reported to be present in 50% of patients. […] up to 75% of affected patients have some form of coagulopathy. […] repeated subclinical trauma and mechanical overload lead to bone collapse and repair (multiple-infarction theory). […] damages result from epiphyseal bone resorption, collapse, and the effect of subsequent repair during the course of disease. […] maternal / passive smoking aggravates.

• #4 Legg–Calvé–Perthes disease overview | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-022-02275-z

  The pathogenesis of LCPD is complex. From a mechanical point of view, deformities in the FH will occur when the forces applied to the FH are greater than its capacity to resist deformation. […] It is suggested that the mechanical properties of infarcted bones are compromised as a result of various mechanisms taking place during different stages of the disease. […] First, in the avascular stage, the calcium increase in the necrotic bone makes it more prone to microdamage, which compromises the mechanical properties of the FH. […] The disease is commonly linked to alterations to thrombophilia or hypercoagulable states, such as factor V Leiden mutation, overactivity of FVIII and prothrombin, alterations in natural anticoagulants like protein C and S, hypofibrinolysis and increased selectins; however, data also suggests that inflammation and endothelium could be important factors in the development of LCPD. […] Avascularity plays a key role in the etiology of LCPD. […] The available information suggests that LCPD has a multifactorial etiology where multiple environmental, metabolic and genetic agents could be involved.

• #5

  https://www.orthobullets.com/pediatrics/4119/legg-calve-perthes-disease

  Legg-Calve-Perthes Disease is an idiopathic avascular necrosis of the proximal femoral epiphysis in children. […] osteonecrosis occurs secondary to disruption of blood supply to femoral head followed by revascularization with subsequent resorption and later collapse. […] creeping substitution provides pathway for remodeling after collapse. […] possible association with abnormal clotting factors (Protein S and Protein C deficiencies) is a controversial etiology. […] thrombophilia has been reported to be present in 50% of patients. […] up to 75% of affected patients have some form of coagulopathy. […] repeated subclinical trauma and mechanical overload lead to bone collapse and repair (multiple-infarction theory). […] damages result from epiphyseal bone resorption, collapse, and the effect of subsequent repair during the course of disease. […] maternal / passive smoking aggravates.

• #6 Frontiers | Progress in understanding Legg–Calvé–Perthes disease etiology from a molecular and cellular biology perspective

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2025.1514302/full

  Some scholars have pointed out that although typical LCPD hip joint imaging changes are observed in these cases, it is difficult to distinguish whether these changes are caused by ischemia or by epiphyseal dysplasia. […] Thrombophilia is a disease caused by abnormal coagulation-related factors. […] Vosmaer et al. (2010) found that factor V Leiden, prothrombin G20210A mutations, Protein-S and Protein-C deficiencies, and elevated factor VIII are all associated with an increased risk of LCPD. […] As early as 1994, a clinical controlled trial led by Glueck et al. (1994) first reported that among 8 LCPD patients, 3 had Protein-C deficiency and 1 had Protein-S deficiency. […] The factor V Leiden mutation is another cause of thrombophilia, and Glueck et al. (1997) initially reported that 8 out of 64 LCPD patients had the factor V Leiden mutation.

• #7 Frontiers | Progress in understanding Legg–Calvé–Perthes disease etiology from a molecular and cellular biology perspective

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2025.1514302/full

  Significant progress has been made in etiological research on LCPD. […] We aim to summarize the current research status from a molecular biology perspective, focusing on aspects like gene mutations, epigenetic modifications, and gene polymorphisms. […] The molecular level is the lowest level at which we currently understand the disease and may be the cause of the disease. […] Previous reports of changes in the molecular level of LCPD may include COL2A1 mutation, tissue factor V Leiden mutation, and IGF-1 dysfunction, but these molecular changes as independent factors to cause the disease remain controversial. […] Research on COL2A1 mutations in femoral head ischemic necrosis began with Liu et al. (2005), who conducted a four-generation pedigree analysis of two families with familial femoral head necrosis.

• #8 Clinical and genetic characteristics of Legg-Calve-Perthes disease – Journal of Musculoskeletal Surgery and Research

  https://journalmsr.com/clinical-and-genetic-characteristics-of-legg-calve-perthes-disease/

  Legg-Calve-Perthes disease (LCPD) is a known childhood form of idiopathic femoral head osteonecrosis. It is characterized by a sequence of events involving the capital femoral epiphysis. The disease process is associated with the disruption of the blood supply to the femoral head. […] The disease etiology is still unknown, however, various factors have been considered for the pathogenesis of LCPD, including very low body weight or short stature at birth, maternal smoking, and secondhand smoke exposure. Interaction of multiple environmental and genetic factors has also been postulated as an underlying player in the development of the disorder. Hypercoagulability may have a major role in LCPD development. […] The cause of the LCPD is largely unknown, though, many experimental and clinical studies provide support to the idea that the temporary disruption of the blood supply to the femoral head is a key event in the pathogenesis of the disease. Various diagnostic tools including selective angiography, bone scintigraphy, perfusion magnetic resonance imaging (MRI), and the biopsy studies from the early stages of the disease show clear indication of disruption of perfusion and bone damage consistent with AVN. The underlying cause may be disruption of supply of blood to the femoral epiphysis due to trauma, coagulopathy, or the use of steroids. Disruption of blood supply might be due to either thrombophilia (an increased tendency for thrombus formation) or hypofibrinolysis (a reduced ability for thrombolysis). The two processes have been suggested to play an essential role in the pathogenesis of osteonecrosis.

• #9 Legg-Calve-Perthes Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK513230/

  Legg-Calve-Perthes disease (LCPD) is idiopathic osteonecrosis or idiopathic avascular necrosis of the capital femoral epiphysis of the femoral head. […] The cause of Legg-Calve-Perthes disease is not known. It may be idiopathic or due to other etiology that would disrupt blood flow to the femoral epiphysis, such as trauma (macro or repetitive microtrauma), coagulopathy, and steroid use. Thrombophilia is present in approximately 50% of patients, and some form of coagulopathy is present in up to 75%. […] Typically, Legg-Calve-Perthes disease includes four phases: Necrosis: Disruption of the blood supply leads to infarction of the femoral capital epiphysis, particularly the subchondral cortical bone. Subsequently, this leads to a cessation of the growth of the ossific nucleus. The infarcted bone softens and dies. Fragmentation: The body reabsorbs the infarcted bone. Reossification: Osteoblastic activity takes over, and the femoral epiphysis reestablishes. Remodeling: The new femoral head may be enlarged or flattened. It reshapes during growth. Those that respond to conservative treatment will usually show healing in 2 to 4 years.

• #10

  https://www.orthobullets.com/pediatrics/4119/legg-calve-perthes-disease

  Legg-Calve-Perthes Disease is an idiopathic avascular necrosis of the proximal femoral epiphysis in children. […] osteonecrosis occurs secondary to disruption of blood supply to femoral head followed by revascularization with subsequent resorption and later collapse. […] creeping substitution provides pathway for remodeling after collapse. […] possible association with abnormal clotting factors (Protein S and Protein C deficiencies) is a controversial etiology. […] thrombophilia has been reported to be present in 50% of patients. […] up to 75% of affected patients have some form of coagulopathy. […] repeated subclinical trauma and mechanical overload lead to bone collapse and repair (multiple-infarction theory). […] damages result from epiphyseal bone resorption, collapse, and the effect of subsequent repair during the course of disease. […] maternal / passive smoking aggravates.

• #11

  https://www.orthobullets.com/pediatrics/4119/legg-calve-perthes-disease

  Legg-Calve-Perthes Disease is an idiopathic avascular necrosis of the proximal femoral epiphysis in children. […] osteonecrosis occurs secondary to disruption of blood supply to femoral head followed by revascularization with subsequent resorption and later collapse. […] creeping substitution provides pathway for remodeling after collapse. […] possible association with abnormal clotting factors (Protein S and Protein C deficiencies) is a controversial etiology. […] thrombophilia has been reported to be present in 50% of patients. […] up to 75% of affected patients have some form of coagulopathy. […] repeated subclinical trauma and mechanical overload lead to bone collapse and repair (multiple-infarction theory). […] damages result from epiphyseal bone resorption, collapse, and the effect of subsequent repair during the course of disease. […] maternal / passive smoking aggravates.

• #12 Clinical and genetic characteristics of Legg-Calve-Perthes disease – Journal of Musculoskeletal Surgery and Research

  https://journalmsr.com/clinical-and-genetic-characteristics-of-legg-calve-perthes-disease/

  Legg-Calve-Perthes disease (LCPD) is a known childhood form of idiopathic femoral head osteonecrosis. It is characterized by a sequence of events involving the capital femoral epiphysis. The disease process is associated with the disruption of the blood supply to the femoral head. […] The disease etiology is still unknown, however, various factors have been considered for the pathogenesis of LCPD, including very low body weight or short stature at birth, maternal smoking, and secondhand smoke exposure. Interaction of multiple environmental and genetic factors has also been postulated as an underlying player in the development of the disorder. Hypercoagulability may have a major role in LCPD development. […] The cause of the LCPD is largely unknown, though, many experimental and clinical studies provide support to the idea that the temporary disruption of the blood supply to the femoral head is a key event in the pathogenesis of the disease. Various diagnostic tools including selective angiography, bone scintigraphy, perfusion magnetic resonance imaging (MRI), and the biopsy studies from the early stages of the disease show clear indication of disruption of perfusion and bone damage consistent with AVN. The underlying cause may be disruption of supply of blood to the femoral epiphysis due to trauma, coagulopathy, or the use of steroids. Disruption of blood supply might be due to either thrombophilia (an increased tendency for thrombus formation) or hypofibrinolysis (a reduced ability for thrombolysis). The two processes have been suggested to play an essential role in the pathogenesis of osteonecrosis.

• #13 Legg Calve Perthes Disease – OrthoPaedia

  https://www.orthopaedia.com/legg-calve-perthes-disease/

  Legg-Calve-Perthes disease, commonly known as Perthes disease, is a hip disorder affecting children that is caused by decreased blood flow to the head of the femur. This results in osteonecrosis (also known as “avascular necrosis”) of the proximal femoral epiphysis (femoral head), with resorption, reossification, and remodeling of the bone. […] In Legg-Calve-Perthes disease, the blood supply is disrupted by an unknown process, and the bone cells begin to die. This process is termed osteonecrosis. […] Loss of blood supply to bone results in ischemia and cell death. In turn, cell death leads to less bone remodeling and poorer structural properties of bone. These weaker properties increase the risk of collapse with load. […] The exact cause of the disruption of the blood supply is not known, although it is believed to be multifactorial. Genetic abnormalities, trauma, coagulopathy, collagenopathy, hyperactivity, and passive smoking exposure are seen with higher prevalence in patients with Perthes, and are therefore thought to possibly have a causative role. […] Another theory links systemic delay in growth and development to the development of Perthes. Delayed bone age has been seen among patients with Legg-Calve-Perthes disease, and therefore, endocrine dysfunction has been implicated as a possible cause.

• #14 Clinical and genetic characteristics of Legg-Calve-Perthes disease – Journal of Musculoskeletal Surgery and Research

  https://journalmsr.com/clinical-and-genetic-characteristics-of-legg-calve-perthes-disease/

  The thrombophilia-based hypothesis (thrombophilia followed by thrombotic venous occlusion of the femoral head) of LCPD is based on the notion that thrombosis selectively blocks the femoral head venous outflow, leading to increased intraosseous pressure, and subsequent AVN. […] Defects in coagulation factors have been considered as one of the possible causes of the impaired supply of blood to the femoral epiphysis. […] The pathogenic process by which mutations in candidate genes confer risk of LCPD and the nature of the interaction between environmental and genetic factors are yet to be identified.

• #15 Legg-Calvé-Perthes Disease | Musculoskeletal Key

  https://musculoskeletalkey.com/legg-calve-perthes-disease-6/

  Many studies have proposed other etiologic factors. Because the pathologic changes seen in the femoral head are likely the result of an ischemic process, various investigators have implicated a disruption of both the arterial and venous systems. […] Some evidence based on angiographic and bone scintigraphic studies suggests that the arterial circulation of the femoral head may be the primary site affected in LCPD. […] Angiographic studies have helped demonstrate the disruption of the blood supply to the proximal femur in patients with LCPD. […] Abnormal venous drainage of the head and neck of the femur has also been noted in patients with LCPD. […] Although these abnormalities in venous outflow are a consistent finding in LCPD, it is unknown whether they are a cause of the disorder or a secondary effect of some other factors involved in the pathogenetic process.

• #16 Legg-Calve-Perthes Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK513230/

  Legg-Calve-Perthes disease (LCPD) is idiopathic osteonecrosis or idiopathic avascular necrosis of the capital femoral epiphysis of the femoral head. […] The cause of Legg-Calve-Perthes disease is not known. It may be idiopathic or due to other etiology that would disrupt blood flow to the femoral epiphysis, such as trauma (macro or repetitive microtrauma), coagulopathy, and steroid use. Thrombophilia is present in approximately 50% of patients, and some form of coagulopathy is present in up to 75%. […] Typically, Legg-Calve-Perthes disease includes four phases: Necrosis: Disruption of the blood supply leads to infarction of the femoral capital epiphysis, particularly the subchondral cortical bone. Subsequently, this leads to a cessation of the growth of the ossific nucleus. The infarcted bone softens and dies. Fragmentation: The body reabsorbs the infarcted bone. Reossification: Osteoblastic activity takes over, and the femoral epiphysis reestablishes. Remodeling: The new femoral head may be enlarged or flattened. It reshapes during growth. Those that respond to conservative treatment will usually show healing in 2 to 4 years.

• #17 Perthes Disease – Legg-Calve-Perthes – OrthoInfo – AAOS

  https://orthoinfo.aaos.org/en/diseases–conditions/perthes-disease

  Perthes disease is a rare childhood condition that affects the hip. It occurs when the blood supply to the rounded head of the femur (thighbone) is temporarily disrupted. Without an adequate blood supply, the bone cells die, a process called avascular necrosis. […] Although the term „disease” is still used, Perthes is really a complex process of stages that can last several years. As the condition progresses, the weakened bone of the head of the femur (the ball of the ball-and-socket joint of the hip) gradually begins to collapse. Over time, the blood supply to the head of the femur returns and the bone begins to grow back. […] The cause of Perthes disease is not known. Some recent studies indicate that there may be a genetic link to the development of Perthes, but more research needs to be conducted.

• #18 Perthes Disease – Legg-Calve-Perthes – OrthoInfo – AAOS

  https://orthoinfo.aaos.org/en/diseases–conditions/perthes-disease

  In the first stage of Perthes disease, the bone in the head of the femur slowly dies. […] There are four stages in Perthes disease: Initial / necrosis, Fragmentation, Reossification, Healed. […] In this stage of the disease, the blood supply to the femoral head is disrupted and bone cells die. The area becomes intensely inflamed and irritated, and your child may begin to show signs of the disease, such as a limp or different way of walking. […] Over a period of 1 to 2 years, the body removes the dead bone beneath the articular cartilage and quickly replaces it with an initial, softer bone. […] In this stage, new, stronger bone develops and begins to take shape in the head of the femur. […] In this stage, the bone regrowth is complete, and the femoral head has reached its final shape. How close the shape is to round will depend on several factors, including the extent of damage that took place during the fragmentation phase and the child’s age at the onset of disease, which affects the potential for bone regrowth.

• #19

  https://journals.lww.com/pedorthopaedics/fulltext/2011/09001/natural_history_of_early_onset_and_late_onset.8.aspx

  Over a period of 2 to 4 years, necrotic avascular bone of the epiphysis gets resorbed and replaced completely by new bone. […] The repair process partly entails resorption of the necrotic bone by osteoclasts and new bone deposition by the osteoblasts by a process of creeping substitution. […] The repair process follows a sequence that can be divided into 4 stages on the basis of the appearance of the femoral head on plain radiographs: avascular necrosis, fragmentation, regeneration, and healed stages. […] The first 3 stages can be further divided into early and late parts of the respective stage. […] In the stage of avascular necrosis, the epiphysis appears dense and sclerotic. […] The dense epiphysis begins to fragment and this stage is heralded by the appearance of 1 or 2 fissures in the epiphysis that run perpendicular to the surface of the epiphysis.

• #20 Legg–Calvé–Perthes disease overview | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-022-02275-z

  The pathogenesis of LCPD is complex. From a mechanical point of view, deformities in the FH will occur when the forces applied to the FH are greater than its capacity to resist deformation. […] It is suggested that the mechanical properties of infarcted bones are compromised as a result of various mechanisms taking place during different stages of the disease. […] First, in the avascular stage, the calcium increase in the necrotic bone makes it more prone to microdamage, which compromises the mechanical properties of the FH. […] The disease is commonly linked to alterations to thrombophilia or hypercoagulable states, such as factor V Leiden mutation, overactivity of FVIII and prothrombin, alterations in natural anticoagulants like protein C and S, hypofibrinolysis and increased selectins; however, data also suggests that inflammation and endothelium could be important factors in the development of LCPD. […] Avascularity plays a key role in the etiology of LCPD. […] The available information suggests that LCPD has a multifactorial etiology where multiple environmental, metabolic and genetic agents could be involved.

• #21

  https://journals.lww.com/pedorthopaedics/fulltext/2011/09001/natural_history_of_early_onset_and_late_onset.8.aspx

  Over a period of 2 to 4 years, necrotic avascular bone of the epiphysis gets resorbed and replaced completely by new bone. […] The repair process partly entails resorption of the necrotic bone by osteoclasts and new bone deposition by the osteoblasts by a process of creeping substitution. […] The repair process follows a sequence that can be divided into 4 stages on the basis of the appearance of the femoral head on plain radiographs: avascular necrosis, fragmentation, regeneration, and healed stages. […] The first 3 stages can be further divided into early and late parts of the respective stage. […] In the stage of avascular necrosis, the epiphysis appears dense and sclerotic. […] The dense epiphysis begins to fragment and this stage is heralded by the appearance of 1 or 2 fissures in the epiphysis that run perpendicular to the surface of the epiphysis.

• #22 Pathogenesis of Legg Calve Perthes Disease : Wheeless’ Textbook of Orthopaedics

  https://www.wheelessonline.com/joints/pathogenesis-of-legg-calve-perthes-disease/

  – following inital ischemic episode, most of the epiphysis is avascular; – while enchondral ossification temporaily halts, the articular cartilage, which is nourished by synovial fluid, continues to grow; – this results in widening of medial cartilage (joint) space smaller ossification center in involved hip; – revascularization occurs from periphery; – resumption of enchondral ossification within the epiphysis begins peripherally and progresses centrally; – new bone is deposited on avascular bone, producing a net increase in bone density; – in subchondral area, bone resorption exceeds new bone formation; – point is reached during resorption when subchondral area becomes weak is prone to collapse

• #23 Legg-Calve-Perthes Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK513230/

  Legg-Calve-Perthes disease (LCPD) is idiopathic osteonecrosis or idiopathic avascular necrosis of the capital femoral epiphysis of the femoral head. […] The cause of Legg-Calve-Perthes disease is not known. It may be idiopathic or due to other etiology that would disrupt blood flow to the femoral epiphysis, such as trauma (macro or repetitive microtrauma), coagulopathy, and steroid use. Thrombophilia is present in approximately 50% of patients, and some form of coagulopathy is present in up to 75%. […] Typically, Legg-Calve-Perthes disease includes four phases: Necrosis: Disruption of the blood supply leads to infarction of the femoral capital epiphysis, particularly the subchondral cortical bone. Subsequently, this leads to a cessation of the growth of the ossific nucleus. The infarcted bone softens and dies. Fragmentation: The body reabsorbs the infarcted bone. Reossification: Osteoblastic activity takes over, and the femoral epiphysis reestablishes. Remodeling: The new femoral head may be enlarged or flattened. It reshapes during growth. Those that respond to conservative treatment will usually show healing in 2 to 4 years.

• #24

  https://journals.lww.com/pedorthopaedics/fulltext/2011/09001/natural_history_of_early_onset_and_late_onset.8.aspx

  Over a period of 2 to 4 years, necrotic avascular bone of the epiphysis gets resorbed and replaced completely by new bone. […] The repair process partly entails resorption of the necrotic bone by osteoclasts and new bone deposition by the osteoblasts by a process of creeping substitution. […] The repair process follows a sequence that can be divided into 4 stages on the basis of the appearance of the femoral head on plain radiographs: avascular necrosis, fragmentation, regeneration, and healed stages. […] The first 3 stages can be further divided into early and late parts of the respective stage. […] In the stage of avascular necrosis, the epiphysis appears dense and sclerotic. […] The dense epiphysis begins to fragment and this stage is heralded by the appearance of 1 or 2 fissures in the epiphysis that run perpendicular to the surface of the epiphysis.

• #25

  https://journals.lww.com/pedorthopaedics/fulltext/2011/09001/natural_history_of_early_onset_and_late_onset.8.aspx

  During this stage, several adverse events that are associated with deformation of the femoral head may occur. […] The most important of these is extrusion of the femoral head; the anterolateral part of the avascular epiphysis comes to lie outside the acetabular margin. […] If untreated, extrusion tends to increase gradually as the disease progresses till the early part of the stage of fragmentation; shortly thereafter, there is an abrupt increase in the degree of extrusion. […] The propensity for deformation of the extruded femoral head has been explained on the basis of biomechanical studies. […] In the early stage of revascularization, new bone forms on the periphery of the necrotic epiphysis; this new woven bone is susceptible to deformation. […] If treatment directed at correction of femoral head extrusion is delayed, irreversible deformation of the femoral head occurs.

• #26 Legg calve perthes | PPT

  https://www.slideshare.net/slideshow/legg-calve-perthes-68909681/68909681

  This document summarizes the pathogenesis and treatment of Legg-Calve-Perthes disease, a childhood hip condition caused by interrupted blood supply to the femoral head. The disease leads to bone death and deformity of the femoral head. […] Pathogenesis a single episode or multiple episodes of infarction Femoral head biopsy specimens patients — dead woven bone superimposed on dead lamellar bone, with the marrow space occupied with dead granulation tissue Initiation — disruption of the blood supply to the capital femoral epiphysis. Disruption of the lateral epiphyseal artery at its origin in 68% of patients in all stages of the disease affects the articular cartilage, epiphysis, physis, and metaphysis trabecular bone and the marrow space necrotic Repair: Osteoclastic bone resorption replaced with fibrovascular tissue necrotic femoral head with decreased mechanical stiffness Microfractures (repeated loading)

• #27 Legg-Calvé-Perthes Disease | Musculoskeletal Key

  https://musculoskeletalkey.com/legg-calve-perthes-disease-3/

  An alternative interpretation of the finding, however, is that a single episode of ischemia produces the disease, but subsequent reinjury or injuries of the revascularized region occur as the result of repeated mechanical overloading and/or further collapse of the femoral head during a vascular repair phase. […] The lack of availability of clinical samples for research has prompted alternative approaches, such as the use of animal models, to investigate the pathogenesis of Perthes disease. […] Key findings from this line of investigation are that the induction of ischemia produces a decrease in the mechanical stiffness of the necrotic femoral head, making it relatively soft in comparison with the normal femoral head, from the early avascular necrotic phase to the latter vascular repair phase of the model.

• #28 Legg-Calve-Perthes Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK513230/

  Legg-Calve-Perthes disease (LCPD) is idiopathic osteonecrosis or idiopathic avascular necrosis of the capital femoral epiphysis of the femoral head. […] The cause of Legg-Calve-Perthes disease is not known. It may be idiopathic or due to other etiology that would disrupt blood flow to the femoral epiphysis, such as trauma (macro or repetitive microtrauma), coagulopathy, and steroid use. Thrombophilia is present in approximately 50% of patients, and some form of coagulopathy is present in up to 75%. […] Typically, Legg-Calve-Perthes disease includes four phases: Necrosis: Disruption of the blood supply leads to infarction of the femoral capital epiphysis, particularly the subchondral cortical bone. Subsequently, this leads to a cessation of the growth of the ossific nucleus. The infarcted bone softens and dies. Fragmentation: The body reabsorbs the infarcted bone. Reossification: Osteoblastic activity takes over, and the femoral epiphysis reestablishes. Remodeling: The new femoral head may be enlarged or flattened. It reshapes during growth. Those that respond to conservative treatment will usually show healing in 2 to 4 years.

• #29 Perthes Disease – Legg-Calve-Perthes – OrthoInfo – AAOS

  https://orthoinfo.aaos.org/en/diseases–conditions/perthes-disease

  In the first stage of Perthes disease, the bone in the head of the femur slowly dies. […] There are four stages in Perthes disease: Initial / necrosis, Fragmentation, Reossification, Healed. […] In this stage of the disease, the blood supply to the femoral head is disrupted and bone cells die. The area becomes intensely inflamed and irritated, and your child may begin to show signs of the disease, such as a limp or different way of walking. […] Over a period of 1 to 2 years, the body removes the dead bone beneath the articular cartilage and quickly replaces it with an initial, softer bone. […] In this stage, new, stronger bone develops and begins to take shape in the head of the femur. […] In this stage, the bone regrowth is complete, and the femoral head has reached its final shape. How close the shape is to round will depend on several factors, including the extent of damage that took place during the fragmentation phase and the child’s age at the onset of disease, which affects the potential for bone regrowth.

• #30

  https://journals.lww.com/pedorthopaedics/fulltext/2011/09001/natural_history_of_early_onset_and_late_onset.8.aspx

  During this stage, several adverse events that are associated with deformation of the femoral head may occur. […] The most important of these is extrusion of the femoral head; the anterolateral part of the avascular epiphysis comes to lie outside the acetabular margin. […] If untreated, extrusion tends to increase gradually as the disease progresses till the early part of the stage of fragmentation; shortly thereafter, there is an abrupt increase in the degree of extrusion. […] The propensity for deformation of the extruded femoral head has been explained on the basis of biomechanical studies. […] In the early stage of revascularization, new bone forms on the periphery of the necrotic epiphysis; this new woven bone is susceptible to deformation. […] If treatment directed at correction of femoral head extrusion is delayed, irreversible deformation of the femoral head occurs.

• #31

  https://journals.lww.com/pedorthopaedics/fulltext/2011/09001/natural_history_of_early_onset_and_late_onset.8.aspx

  The disease per se is a self-limiting disorder; the blood supply to the femoral epiphysis gets restored spontaneously. […] Revascularization of bone can occur by 1 of 2 mechanisms; the first is by rapid recanalization of existing vessels, which occurs within weeks, whereas the second is by formation of new vessels or neovascularization over a period of months to years. […] The pattern of revascularization by recanalization observed on an isotope scan is the appearance of a lateral column signifying a good prognosis, whereas neovascularization is characterized by scintigraphic appearances referred to as base filling and mushrooming, which signify a poor prognosis. […] While the vascular repair process is occurring, characteristic changes take place in the femoral epiphysis and metaphysis, the acetabulum, and the femoro-acetabular relationship as the disease evolves.

• #32

  https://journals.lww.com/pedorthopaedics/fulltext/2011/09001/natural_history_of_early_onset_and_late_onset.8.aspx

  The disease per se is a self-limiting disorder; the blood supply to the femoral epiphysis gets restored spontaneously. […] Revascularization of bone can occur by 1 of 2 mechanisms; the first is by rapid recanalization of existing vessels, which occurs within weeks, whereas the second is by formation of new vessels or neovascularization over a period of months to years. […] The pattern of revascularization by recanalization observed on an isotope scan is the appearance of a lateral column signifying a good prognosis, whereas neovascularization is characterized by scintigraphic appearances referred to as base filling and mushrooming, which signify a poor prognosis. […] While the vascular repair process is occurring, characteristic changes take place in the femoral epiphysis and metaphysis, the acetabulum, and the femoro-acetabular relationship as the disease evolves.

• #33 Legg-Calve-Perthes Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK513230/

  Legg-Calve-Perthes disease (LCPD) is idiopathic osteonecrosis or idiopathic avascular necrosis of the capital femoral epiphysis of the femoral head. […] The cause of Legg-Calve-Perthes disease is not known. It may be idiopathic or due to other etiology that would disrupt blood flow to the femoral epiphysis, such as trauma (macro or repetitive microtrauma), coagulopathy, and steroid use. Thrombophilia is present in approximately 50% of patients, and some form of coagulopathy is present in up to 75%. […] Typically, Legg-Calve-Perthes disease includes four phases: Necrosis: Disruption of the blood supply leads to infarction of the femoral capital epiphysis, particularly the subchondral cortical bone. Subsequently, this leads to a cessation of the growth of the ossific nucleus. The infarcted bone softens and dies. Fragmentation: The body reabsorbs the infarcted bone. Reossification: Osteoblastic activity takes over, and the femoral epiphysis reestablishes. Remodeling: The new femoral head may be enlarged or flattened. It reshapes during growth. Those that respond to conservative treatment will usually show healing in 2 to 4 years.

• #34 Perthes Disease – Legg-Calve-Perthes – OrthoInfo – AAOS

  https://orthoinfo.aaos.org/en/diseases–conditions/perthes-disease

  In the first stage of Perthes disease, the bone in the head of the femur slowly dies. […] There are four stages in Perthes disease: Initial / necrosis, Fragmentation, Reossification, Healed. […] In this stage of the disease, the blood supply to the femoral head is disrupted and bone cells die. The area becomes intensely inflamed and irritated, and your child may begin to show signs of the disease, such as a limp or different way of walking. […] Over a period of 1 to 2 years, the body removes the dead bone beneath the articular cartilage and quickly replaces it with an initial, softer bone. […] In this stage, new, stronger bone develops and begins to take shape in the head of the femur. […] In this stage, the bone regrowth is complete, and the femoral head has reached its final shape. How close the shape is to round will depend on several factors, including the extent of damage that took place during the fragmentation phase and the child’s age at the onset of disease, which affects the potential for bone regrowth.

• #35

  https://journals.lww.com/pedorthopaedics/fulltext/2011/09001/natural_history_of_early_onset_and_late_onset.8.aspx

  Gradually, mature lamellar bone replaces the dead bone and once this process is complete the disease is considered to have healed. […] The duration of each of these stages of evolution of the disease varies a great deal with the duration of the earlier stages being significantly lesser than the later stages. […] During the course of the disease, osteoporosis of the metaphysis may develop and in some children a cyst may be seen in the metaphysis, abutting against the growth plate. […] There is no consensus on the exact nature of the underlying pathology of these metaphyseal cysts. […] The true cysts are located in the metaphysis without any epiphyseal connection, whereas false cysts have an epiphyseal extension. […] Metaphyseal cysts and osteoporosis are most frequently seen during the stage of fragmentation and they resolve completely by the time the disease heals.

• #36 Legg-Calve-Perthes Disease | PM&R KnowledgeNow

  https://now.aapmr.org/legg-calve-perthe-disease/

  This may result in deformities in the FH and epiphyseal growth plate. […] The shape of the FH at the time of healing is a determinant for the risk of degenerative arthritis. If the FH is spherical when the disease heals, it is likely that degenerative arthritis will not develop. […] Antiresorptive agents may provide useful adjunctive therapy. Animal studies of ischemic osteonecrosis of hip indicated that combined treatment of bone morphogenetic protein (BMP)-2 with bisphosphonates can decrease bone resorption, increase new bone formation and preserve the femoral head shape. […] There is a need for well designed, controlled studies to explore new treatment options for advanced LCPD, since neither conservative nor operative management showed desirable outcomes.

• #37

  https://journals.lww.com/pedorthopaedics/fulltext/2011/09001/natural_history_of_early_onset_and_late_onset.8.aspx

  Gradually, mature lamellar bone replaces the dead bone and once this process is complete the disease is considered to have healed. […] The duration of each of these stages of evolution of the disease varies a great deal with the duration of the earlier stages being significantly lesser than the later stages. […] During the course of the disease, osteoporosis of the metaphysis may develop and in some children a cyst may be seen in the metaphysis, abutting against the growth plate. […] There is no consensus on the exact nature of the underlying pathology of these metaphyseal cysts. […] The true cysts are located in the metaphysis without any epiphyseal connection, whereas false cysts have an epiphyseal extension. […] Metaphyseal cysts and osteoporosis are most frequently seen during the stage of fragmentation and they resolve completely by the time the disease heals.

• #38 Legg-Calve-Perthes Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK513230/

  Legg-Calve-Perthes disease (LCPD) is idiopathic osteonecrosis or idiopathic avascular necrosis of the capital femoral epiphysis of the femoral head. […] The cause of Legg-Calve-Perthes disease is not known. It may be idiopathic or due to other etiology that would disrupt blood flow to the femoral epiphysis, such as trauma (macro or repetitive microtrauma), coagulopathy, and steroid use. Thrombophilia is present in approximately 50% of patients, and some form of coagulopathy is present in up to 75%. […] Typically, Legg-Calve-Perthes disease includes four phases: Necrosis: Disruption of the blood supply leads to infarction of the femoral capital epiphysis, particularly the subchondral cortical bone. Subsequently, this leads to a cessation of the growth of the ossific nucleus. The infarcted bone softens and dies. Fragmentation: The body reabsorbs the infarcted bone. Reossification: Osteoblastic activity takes over, and the femoral epiphysis reestablishes. Remodeling: The new femoral head may be enlarged or flattened. It reshapes during growth. Those that respond to conservative treatment will usually show healing in 2 to 4 years.

• #39 Legg-Calvé-Perthes Disease | Musculoskeletal Key

  https://musculoskeletalkey.com/legg-calve-perthes-disease-3/

  A permanent deformity of the femoral head is the most important sequela of Perthes disease. […] Biological and mechanical factors contribute to the pathogenesis of the femoral head deformity. […] Recent studies on the causes of Legg-Calv-Perthes disease have described type II collagen mutation as a potential cause of the disease in a limited number of inherited, bilateral cases in Asian families. […] Although the cause of disruption of the blood supply to the femoral head remains unknown, further insight into the pathogenesis of a femoral head deformity has been gained through experimental studies using animal models of ischemic osteonecrosis. […] These studies reveal that mechanical and biological factors contribute to the pathogenesis of the femoral head deformity following ischemic necrosis.

• #40 Effectiveness of therapeutic methods for Legg-Calvé-Perthes disease according to staging, limits of conservative treatment: a systematic review with meta-analysis | Published in Orthopedic Reviews

  https://orthopedicreviews.openmedicalpublishing.org/article/122123

  Necrosis leads to damage to bone cells, osteoblasts and osteoclasts, causing microfractures to go unidentified and/or unrepaired. […] Then, in the revascularization phase, the necrotic bone will be resorbed, further affecting the mechanical properties. […] The hip is one of the main load-bearing joints, so it is important to consider the forces applied to the joint, as these influence the degree of deformity of the femoral head. […] The duration of each phase varies greatly, however, in general, the necrosis and fragmentation phase lasts around six months; the reossification phase, from 18 months to three years; and the final phase, until bone maturity. […] Femoral head deformities occur when the forces applied to the femoral head are greater than its capacity to resist the deformity, from a mechanical point of view.

• #41 Legg–Calvé–Perthes disease overview | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-022-02275-z

  The pathogenesis of LCPD is complex. From a mechanical point of view, deformities in the FH will occur when the forces applied to the FH are greater than its capacity to resist deformation. […] It is suggested that the mechanical properties of infarcted bones are compromised as a result of various mechanisms taking place during different stages of the disease. […] First, in the avascular stage, the calcium increase in the necrotic bone makes it more prone to microdamage, which compromises the mechanical properties of the FH. […] The disease is commonly linked to alterations to thrombophilia or hypercoagulable states, such as factor V Leiden mutation, overactivity of FVIII and prothrombin, alterations in natural anticoagulants like protein C and S, hypofibrinolysis and increased selectins; however, data also suggests that inflammation and endothelium could be important factors in the development of LCPD. […] Avascularity plays a key role in the etiology of LCPD. […] The available information suggests that LCPD has a multifactorial etiology where multiple environmental, metabolic and genetic agents could be involved.

• #42 Effectiveness of therapeutic methods for Legg-Calvé-Perthes disease according to staging, limits of conservative treatment: a systematic review with meta-analysis | Published in Orthopedic Reviews

  https://orthopedicreviews.openmedicalpublishing.org/article/122123

  Necrosis leads to damage to bone cells, osteoblasts and osteoclasts, causing microfractures to go unidentified and/or unrepaired. […] Then, in the revascularization phase, the necrotic bone will be resorbed, further affecting the mechanical properties. […] The hip is one of the main load-bearing joints, so it is important to consider the forces applied to the joint, as these influence the degree of deformity of the femoral head. […] The duration of each phase varies greatly, however, in general, the necrosis and fragmentation phase lasts around six months; the reossification phase, from 18 months to three years; and the final phase, until bone maturity. […] Femoral head deformities occur when the forces applied to the femoral head are greater than its capacity to resist the deformity, from a mechanical point of view.

• #43 Effectiveness of therapeutic methods for Legg-Calvé-Perthes disease according to staging, limits of conservative treatment: a systematic review with meta-analysis | Published in Orthopedic Reviews

  https://orthopedicreviews.openmedicalpublishing.org/article/122123

  Necrosis leads to damage to bone cells, osteoblasts and osteoclasts, causing microfractures to go unidentified and/or unrepaired. […] Then, in the revascularization phase, the necrotic bone will be resorbed, further affecting the mechanical properties. […] The hip is one of the main load-bearing joints, so it is important to consider the forces applied to the joint, as these influence the degree of deformity of the femoral head. […] The duration of each phase varies greatly, however, in general, the necrosis and fragmentation phase lasts around six months; the reossification phase, from 18 months to three years; and the final phase, until bone maturity. […] Femoral head deformities occur when the forces applied to the femoral head are greater than its capacity to resist the deformity, from a mechanical point of view.

• #44 Legg-Calvé-Perthes Disease | Musculoskeletal Key

  https://musculoskeletalkey.com/legg-calve-perthes-disease-3/

  The mechanical compromise observed in the avascular necrotic phase may be due to necrosis of the deep layer of the articular cartilage, changes in the material properties of calcified cartilage and trabecular bone in the infarcted head, and possible accumulation of microfractures in the necrotic bone. […] Vascular invasion and subsequent resorption of necrotic bone further compromise the mechanical properties of the infarcted head in the vascular repair phase. […] It is postulated that the weakened femoral head begins to deform when its ability to resist deformation falls below a critical level surpassed by hip joint loading. […] Inhibition of bone resorption using antiresorptive agents, such as bisphosphonates and receptor activator of nuclear factor (NF)B ligand (RANKL) inhibitor, has been shown to decrease the deformity in animal studies, indicating that the resorptive process is an important component of the pathogenesis of femoral head deformity in these models.

• #45 Legg-Calvé-Perthes Disease | Musculoskeletal Key

  https://musculoskeletalkey.com/legg-calve-perthes-disease-3/

  The mechanical compromise observed in the avascular necrotic phase may be due to necrosis of the deep layer of the articular cartilage, changes in the material properties of calcified cartilage and trabecular bone in the infarcted head, and possible accumulation of microfractures in the necrotic bone. […] Vascular invasion and subsequent resorption of necrotic bone further compromise the mechanical properties of the infarcted head in the vascular repair phase. […] It is postulated that the weakened femoral head begins to deform when its ability to resist deformation falls below a critical level surpassed by hip joint loading. […] Inhibition of bone resorption using antiresorptive agents, such as bisphosphonates and receptor activator of nuclear factor (NF)B ligand (RANKL) inhibitor, has been shown to decrease the deformity in animal studies, indicating that the resorptive process is an important component of the pathogenesis of femoral head deformity in these models.

• #46 Legg-Calvé-Perthes Disease | Musculoskeletal Key

  https://musculoskeletalkey.com/legg-calve-perthes-disease-3/

  The mechanical compromise observed in the avascular necrotic phase may be due to necrosis of the deep layer of the articular cartilage, changes in the material properties of calcified cartilage and trabecular bone in the infarcted head, and possible accumulation of microfractures in the necrotic bone. […] Vascular invasion and subsequent resorption of necrotic bone further compromise the mechanical properties of the infarcted head in the vascular repair phase. […] It is postulated that the weakened femoral head begins to deform when its ability to resist deformation falls below a critical level surpassed by hip joint loading. […] Inhibition of bone resorption using antiresorptive agents, such as bisphosphonates and receptor activator of nuclear factor (NF)B ligand (RANKL) inhibitor, has been shown to decrease the deformity in animal studies, indicating that the resorptive process is an important component of the pathogenesis of femoral head deformity in these models.

• #47 Legg-Calvé-Perthes Disease | Musculoskeletal Key

  https://musculoskeletalkey.com/legg-calve-perthes-disease-3/

  The mechanical compromise observed in the avascular necrotic phase may be due to necrosis of the deep layer of the articular cartilage, changes in the material properties of calcified cartilage and trabecular bone in the infarcted head, and possible accumulation of microfractures in the necrotic bone. […] Vascular invasion and subsequent resorption of necrotic bone further compromise the mechanical properties of the infarcted head in the vascular repair phase. […] It is postulated that the weakened femoral head begins to deform when its ability to resist deformation falls below a critical level surpassed by hip joint loading. […] Inhibition of bone resorption using antiresorptive agents, such as bisphosphonates and receptor activator of nuclear factor (NF)B ligand (RANKL) inhibitor, has been shown to decrease the deformity in animal studies, indicating that the resorptive process is an important component of the pathogenesis of femoral head deformity in these models.

• #48 Investigating Legg-calve-perthes Disease: A Comprehensive Review of Diagnosis Management and Current Treatment Options – Journal of Pediatrics Review

  https://jpr.mazums.ac.ir/browse.php?a_id=606&sid=1&slc_lang=en&html=1

  The pathological progression of LCPD affects multiple parts of the FH, including the articular cartilage, epiphysis, physis, and metaphysis, leading to the destruction of trabecular bone microarchitecture and necrosis in the bone marrow. […] The disruption of blood supply can result in growth cessation of the epiphysis, necrosis of the deep layer of articular cartilage, an increase in vascular endothelial growth factor (VEGF), a rise in vascularization, and deformity. […] Following revascularization, the primary reparative response is osteoclastic bone resorption which causes the normal tissue of the FH to be replaced by fibrovascular tissue. […] Neutrophils and macrophages are the most prevalent inflammatory cells involved in the pathogenesis of osteonecrosis, resulting in macroscopic subchondral collapse and subsequent joint deterioration. […] Disruption in blood supply causes ischemia of the covering cartilage and flattening of the head articulates with the acetabulum, which causes secondary osteoarthritis.

• #49 Legg-Calvé-Perthes Disease | Musculoskeletal Key

  https://musculoskeletalkey.com/legg-calve-perthes-disease-3/

  The mechanical compromise observed in the avascular necrotic phase may be due to necrosis of the deep layer of the articular cartilage, changes in the material properties of calcified cartilage and trabecular bone in the infarcted head, and possible accumulation of microfractures in the necrotic bone. […] Vascular invasion and subsequent resorption of necrotic bone further compromise the mechanical properties of the infarcted head in the vascular repair phase. […] It is postulated that the weakened femoral head begins to deform when its ability to resist deformation falls below a critical level surpassed by hip joint loading. […] Inhibition of bone resorption using antiresorptive agents, such as bisphosphonates and receptor activator of nuclear factor (NF)B ligand (RANKL) inhibitor, has been shown to decrease the deformity in animal studies, indicating that the resorptive process is an important component of the pathogenesis of femoral head deformity in these models.

• #50

  https://journals.lww.com/pedorthopaedics/fulltext/2011/09001/natural_history_of_early_onset_and_late_onset.8.aspx

  Gradually, mature lamellar bone replaces the dead bone and once this process is complete the disease is considered to have healed. […] The duration of each of these stages of evolution of the disease varies a great deal with the duration of the earlier stages being significantly lesser than the later stages. […] During the course of the disease, osteoporosis of the metaphysis may develop and in some children a cyst may be seen in the metaphysis, abutting against the growth plate. […] There is no consensus on the exact nature of the underlying pathology of these metaphyseal cysts. […] The true cysts are located in the metaphysis without any epiphyseal connection, whereas false cysts have an epiphyseal extension. […] Metaphyseal cysts and osteoporosis are most frequently seen during the stage of fragmentation and they resolve completely by the time the disease heals.

• #51

  https://journals.lww.com/pedorthopaedics/fulltext/2011/09001/natural_history_of_early_onset_and_late_onset.8.aspx

  Widening of the metaphysis is another phenomenon noted in several children; it occurs as a consequence of splaying out of the growth plate as the epiphysis flattens. […] The extent of metaphyseal widening correlates quite closely with the extent to which the femoral head enlarges, and greater the degree of metaphyseal widening the poorer the final outcome. […] Histologic, ultrastructural, and histochemical changes have been demonstrated in the physeal cartilage in LCPD, including a reduction in collagen and proteoglycan granules and the presence of numerous large lipid inclusions. […] In a proportion of children, premature fusion of the capital femoral growth plate occurs as a consequence of these physeal abnormalities; this results in diminished linear growth of the femoral neck. […] The greater trochanter continues to grow and by skeletal maturity the trochanter may outgrow the femoral neck.

• #52

  https://journals.lww.com/pedorthopaedics/fulltext/2011/09001/natural_history_of_early_onset_and_late_onset.8.aspx

  The foreshortened femoral neck and overriding trochanter results in altered mechanics of the hip and a Trendelenburg gait. […] Changes in the acetabulum are also seen in children with LCPD; they include articular cartilage thickening, alterations in the shape and dimensions of the acetabulum, and premature closure of the triradiate cartilage. […] Although some of these changes noted in the acetabulum are secondary to alterations in the shape and size of the femoral head, some changes are noted very early in the course of the disease and they seem to have a bearing on the outcome.

• #53 A retrospective study describing the acetabular consequences of Legg- Calve-Perthes disease | BMC Musculoskeletal Disorders | Full Text

  https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-024-07852-w

  Legg Calve Perthes disease (LCPD) is a paediatric hip disorder caused by ischemia of the femoral epiphysis, causing femoral head deformity when untreated. […] The unchanged shape of the acetabulum facilitates the restoration of the sphericity of the proximal femoral epiphysis. However, alterations in the acetabulum’s shape and inadequate coverage of the deformed femoral head can potentially lead to early onset osteoarthritis of the hip. […] Acetabular retroversion significantly influences femoral head coverage and the orientation of the lateral wall of the acetabulum. Moreover, the acetabulum plays a pivotal role in the remodelling of the proximal femoral epiphysis and, consequently, the ultimate outcome of the disease. […] The majority of authors consider that the initial changes originate in the shape of the femoral head with a normal acetabulum which secondarily becomes deformed. However, other authors have previously speculated that in hips with LCPD, the primary deformity is the retroverted acetabulum which subsequently results in altered loading patterns of the joint and stress on the blood supply of the femoral head, causing secondary deformity of the femoral head.

• #54 A retrospective study describing the acetabular consequences of Legg- Calve-Perthes disease | BMC Musculoskeletal Disorders | Full Text

  https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-024-07852-w

  Larson et al. found that acetabular retroversion is more common in pediatric patients with LCPD than in pediatric control subjects, supporting the theory that retroversion may play a critical role in the pathogenesis of LCPD and that the acetabular abnormality should be taken into account during treatment of the disorder.

• #55 Frontiers | Progress in understanding Legg–Calvé–Perthes disease etiology from a molecular and cellular biology perspective

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2025.1514302/full

  Legg–Calvé–Perthes disease (LCPD) is a hip disease caused by ischemia of the femoral epiphysis in children, which occurs in children aged 4–8 years (mean 6.5 years), with a male-to-female ratio of about 4:1. […] In recent years, a considerable amount of research has been carried out on the etiology of the disease, and the development of the disease is believed to involve a variety of molecular biological alterations, such as the COL2A1 mutation, which may be one of the causes of necrotic collapses of the epiphyseal cartilage matrix in LCPD. […] The in-depth study of LCPD cell biology has facilitated the suggestion regarding structural and/or functional abnormalities of microvascular endothelial cells in LCPD. […] Abnormal activation of osteoclasts, ischemic damage to epiphyseal cartilage, and activation of the bone marrow immune system all play important roles in the onset and progression of the disease.

• #56 Frontiers | Progress in understanding Legg–Calvé–Perthes disease etiology from a molecular and cellular biology perspective

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2025.1514302/full

  Significant progress has been made in etiological research on LCPD. […] We aim to summarize the current research status from a molecular biology perspective, focusing on aspects like gene mutations, epigenetic modifications, and gene polymorphisms. […] The molecular level is the lowest level at which we currently understand the disease and may be the cause of the disease. […] Previous reports of changes in the molecular level of LCPD may include COL2A1 mutation, tissue factor V Leiden mutation, and IGF-1 dysfunction, but these molecular changes as independent factors to cause the disease remain controversial. […] Research on COL2A1 mutations in femoral head ischemic necrosis began with Liu et al. (2005), who conducted a four-generation pedigree analysis of two families with familial femoral head necrosis.

• #57 Frontiers | Progress in understanding Legg–Calvé–Perthes disease etiology from a molecular and cellular biology perspective

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2025.1514302/full

  Epigenetics suggests that acquired phenotypes can be inherited, and non-genetic changes influence the genotype. […] In summary, analyzing global DNA methylation levels and non-coding RNA expression in patients provides the first epigenetic explanation for LCPD etiology. […] Changes in DNA bases result in gene mutations, while natural variations in single nucleotides cause DNA sequence polymorphisms. […] The necrotic collapse of the femoral head in LCPD patients is related to epiphyseal cartilage degeneration. […] The repair process in LCPD is also accompanied by chronic inflammation. […] Osteoclasts are the only known cells responsible for bone resorption in the human body, and this discussion shows that their abnormal activation plays a role in the development of LCPD and contributes to deformity during healing. […] Overall, while the cause of LCPD remains unclear, advancements in molecular and cellular biology offer new perspectives for basic research into the disease.

• #58 Frontiers | Progress in understanding Legg–Calvé–Perthes disease etiology from a molecular and cellular biology perspective

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2025.1514302/full

  Epigenetics suggests that acquired phenotypes can be inherited, and non-genetic changes influence the genotype. […] In summary, analyzing global DNA methylation levels and non-coding RNA expression in patients provides the first epigenetic explanation for LCPD etiology. […] Changes in DNA bases result in gene mutations, while natural variations in single nucleotides cause DNA sequence polymorphisms. […] The necrotic collapse of the femoral head in LCPD patients is related to epiphyseal cartilage degeneration. […] The repair process in LCPD is also accompanied by chronic inflammation. […] Osteoclasts are the only known cells responsible for bone resorption in the human body, and this discussion shows that their abnormal activation plays a role in the development of LCPD and contributes to deformity during healing. […] Overall, while the cause of LCPD remains unclear, advancements in molecular and cellular biology offer new perspectives for basic research into the disease.

• #59

  https://jposna.org/index.php/jposna/article/view/730

  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. […] 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. […] Specifically, it emphasizes the importance of supporting chondrification and the production of VEGF rather than focusing solely on anti-resorptive and osteogenics.

• #60

  https://journals.lww.com/pedorthopaedics/fulltext/2011/09001/natural_history_of_early_onset_and_late_onset.8.aspx

  Legg-Calve-Perthes disease develops after interruption of the blood supply to the capital femoral epiphysis. This results in various changes in the femoral epiphysis and metaphysis, the capital femoral epiphysis, growth plate, and the acetabulum. […] The precise cause of LCPD still eludes us, but it is clear that a vascular insult is the final precipitating episode that leads to the disease. […] Studies on necropsy specimens suggest that 2 infarcts precede the clinical onset of LCPD. […] The blood supply to the capital femoral epiphysis during a period in childhood is solely from the lateral epiphyseal vessels and LCPD seems to develop at this time. […] Isotope and magnetic resonance imaging scans confirm clearly that the disease is characterized by avascularity of the femoral epiphysis and they can define the extent of the epiphysis that is devoid of blood supply much before the changes of avascularity are evident on plain radiographs.

• #61 Pathophysiology, Classifications, and Natural History of Perthes Disease – EM consulte

  https://www.em-consulte.com/article/306456/pathophysiology-classifications-and-natural-histor

  Since the original reports of Legg-Calv-Perthes disease (LCPD), much research effort has been undertaken to improve understanding of this idiopathic hip disorder. […] Although the cause of LCPD remains largely unknown, some insight has been gained on its pathophysiology through experimental studies using animal models of ischemic necrosis. […] The few available clinical studies on the natural history of LCPD suggest that femoral head deformity is well tolerated in short and intermediate terms, but 50% of patients develop disabling arthritis in the sixth decade of life.

• #62 Legg-Calve-Perthes Disease | PM&R KnowledgeNow

  https://now.aapmr.org/legg-calve-perthe-disease/

  This may result in deformities in the FH and epiphyseal growth plate. […] The shape of the FH at the time of healing is a determinant for the risk of degenerative arthritis. If the FH is spherical when the disease heals, it is likely that degenerative arthritis will not develop. […] Antiresorptive agents may provide useful adjunctive therapy. Animal studies of ischemic osteonecrosis of hip indicated that combined treatment of bone morphogenetic protein (BMP)-2 with bisphosphonates can decrease bone resorption, increase new bone formation and preserve the femoral head shape. […] There is a need for well designed, controlled studies to explore new treatment options for advanced LCPD, since neither conservative nor operative management showed desirable outcomes.

• #63 Perthes Disease – Legg-Calve-Perthes – OrthoInfo – AAOS

  https://orthoinfo.aaos.org/en/diseases–conditions/perthes-disease

  If left untreated, the femoral head can deform and not fit well within the acetabulum (hip socket), which can lead to further hip problems in adulthood, such as early onset of arthritis. […] The most common surgical procedure for treating Perthes disease is an osteotomy. In this type of procedure, the bone is cut and repositioned to keep the femoral head snugly within the acetabulum.

• #64 Pathophysiology, Classifications, and Natural History of Perthes Disease – EM consulte

  https://www.em-consulte.com/article/306456/pathophysiology-classifications-and-natural-histor

  Since the original reports of Legg-Calv-Perthes disease (LCPD), much research effort has been undertaken to improve understanding of this idiopathic hip disorder. […] Although the cause of LCPD remains largely unknown, some insight has been gained on its pathophysiology through experimental studies using animal models of ischemic necrosis. […] The few available clinical studies on the natural history of LCPD suggest that femoral head deformity is well tolerated in short and intermediate terms, but 50% of patients develop disabling arthritis in the sixth decade of life.

• #65 Legg–Calvé–Perthes disease overview | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-022-02275-z

  The pathogenesis of LCPD is complex. From a mechanical point of view, deformities in the FH will occur when the forces applied to the FH are greater than its capacity to resist deformation. […] It is suggested that the mechanical properties of infarcted bones are compromised as a result of various mechanisms taking place during different stages of the disease. […] First, in the avascular stage, the calcium increase in the necrotic bone makes it more prone to microdamage, which compromises the mechanical properties of the FH. […] The disease is commonly linked to alterations to thrombophilia or hypercoagulable states, such as factor V Leiden mutation, overactivity of FVIII and prothrombin, alterations in natural anticoagulants like protein C and S, hypofibrinolysis and increased selectins; however, data also suggests that inflammation and endothelium could be important factors in the development of LCPD. […] Avascularity plays a key role in the etiology of LCPD. […] The available information suggests that LCPD has a multifactorial etiology where multiple environmental, metabolic and genetic agents could be involved.

• #66 Molecular foundations of the etiology and pathogenesis of Legg-Calve-Perthes disease and prospects for targeted therapy: A literature review – Shabaldin – Pediatric Traumatology, Orthopaedics and Reconstructive Surgery

  https://bakhtiniada.ru/turner/article/view/101679

  The etiology and pathogenesis of the development of LeggCalvePerthes disease, despite intensive research, remains not fully understood. […] Most studies have concluded about the multifactorial genesis of the development of hip osteochondropathy. […] A complete understanding of all elements of pathogenesis leading to the manifestation and the progressive development of aseptic necrosis make it possible to develop targeted antiresorptive therapy. […] At present, several studies have investigated impaired functioning of signaling pathways that influence bone homeostasis during the development of LeggCalvePerthes disease. […] The pathogenesis of LeggCalvePerthes disease is characterized by significant genetic heterogeneity with the induction of various mediators of inflammation, angiogenesis, and osteogenesis, depending on the disease stage. […] Investigating features of impaired bone homeostasis regulation in the case of LeggCalvePerthes disease at the molecular and cellular level opens up opportunities for the development and clinical application of personalized therapy.

• #67 Molecular foundations of the etiology and pathogenesis of Legg-Calve-Perthes disease and prospects for targeted therapy: A literature review – Shabaldin – Pediatric Traumatology, Orthopaedics and Reconstructive Surgery

  https://journals.eco-vector.com/turner/article/view/101679

  The etiology and pathogenesis of the development of LeggCalvePerthes disease, despite intensive research, remains not fully understood. […] Most studies have concluded about the multifactorial genesis of the development of hip osteochondropathy. […] Moreover, a complete understanding of all elements of pathogenesis leading to the manifestation and the progressive development of aseptic necrosis make it possible to develop targeted antiresorptive therapy. […] At present, several studies have investigated impaired functioning of signaling pathways that influence bone homeostasis during the development of LeggCalvePerthes disease. […] In addition, impaired metabolism in avascular necrosis is characterized by significant complexity and heterogeneity, which is based on aseptic inflammation associated with ischemic stress.

• #68 Molecular foundations of the etiology and pathogenesis of Legg-Calve-Perthes disease and prospects for targeted therapy: A literature review – Shabaldin – Pediatric Traumatology, Orthopaedics and Reconstructive Surgery

  https://journals.eco-vector.com/turner/article/view/101679

  Concepts of antiresorptive therapy were developed based on the results of studies on the pathogenesis of LeggCalvePerthes disease. […] The pathogenesis of LeggCalvePerthes disease is characterized by significant genetic heterogeneity with the induction of various mediators of inflammation, angiogenesis, and osteogenesis, depending on the disease stage. […] Investigating features of impaired bone homeostasis regulation in the case of LeggCalvePerthes disease at the molecular and cellular level opens up opportunities for the development and clinical application of personalized therapy.

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