Materiały źródłowe

• #1 Legg-Calve-Perthes disease | Altru Health System

  https://www.altru.org/health-library/conditions/legg-calve-perthes-disease

  Legg-Calve-Perthes (LEG-kahl-VAY-PER-tuz) disease is a childhood condition that occurs when blood supply to the ball part (femoral head) of the hip joint is temporarily interrupted and the bone begins to die. […] Perthes disease occurs when too little blood reaches the ball portion of the hip joint for a short time. Without enough blood, this bone becomes weak and collapses. The cause of the reduced blood flow is unknown.

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

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

  LeggCalvPerthes Disease (LCPD) is a necrosis of the femoral head which affects the range of motion of the hips. Its incidence is variable, ranging from 0.4/100,000 to 29.0/ 100,000 children. […] Although LCPD was first described in the beginning of the past century and has been studied for more than 100 years, limited is known about its etiology. […] This review suggests that LCPD has a multifactorial etiology where environmental, metabolic and genetic agents could be involved. […] The cause of LCPD is unknown. Different etiologies have been proposed; nevertheless, LCPD may be caused by multiple etiologic factors that share a common final pathogenic pathway. A new perspective is that LCPD is a multifactorial disease caused by a combination of environmental, metabolic and genetic factors.

• #3 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. […] 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.

• #4 Legg-Calvé-Perthes disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/legg-calve-perthes-disease/

  Legg-Calvés-Perthes disease is a bone disorder that affects the hips. […] The exact cause of Legg-Calvés-Perthes disease is not known. Some researchers have suggested that the condition is multifactorial, which means it is caused by a combination of genetic, lifestyle, environmental, and metabolic factors. Joint stress, blood clotting abnormalities, malnutrition, obesity, and exposure to cigarette smoke may all contribute to the development of Legg-Calvés-Perthes disease. […] Some cases of Legg-Calvés-Perthes disease were previously thought to be caused by variants (also called mutations) in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen, which is found in connective tissues. Many researchers today, however, do not believe that variants in the COL2A1 gene cause Legg-Calvés-Perthes disease. Studies are investigating the potential causes of Legg-Calvés-Perthes disease, including the role genetics might play in this disorder.

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

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

  LeggCalvPerthes Disease (LCPD) is a necrosis of the femoral head which affects the range of motion of the hips. Its incidence is variable, ranging from 0.4/100,000 to 29.0/ 100,000 children. […] Although LCPD was first described in the beginning of the past century and has been studied for more than 100 years, limited is known about its etiology. […] This review suggests that LCPD has a multifactorial etiology where environmental, metabolic and genetic agents could be involved. […] The cause of LCPD is unknown. Different etiologies have been proposed; nevertheless, LCPD may be caused by multiple etiologic factors that share a common final pathogenic pathway. A new perspective is that LCPD is a multifactorial disease caused by a combination of environmental, metabolic and genetic factors.

• #6 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. […] 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. […] A few proposed risk factors include passive exposure to smoke and hyperactivity, although there is no known mechanism linking these risk factors to the development of Legg-Calve-Perthes disease. […] Although the exact cause of Perthes disease is unknown, many environmental and holistic risk factors have been proposed.

• #7 Legg–Calvé–Perthes disease – Wikipedia

  https://en.wikipedia.org/wiki/Legg%E2%80%93Calv%C3%A9%E2%80%93Perthes_disease

  Legg-Calv-Perthes disease (LCPD) is a childhood hip disorder initiated by a disruption of blood flow to the head of the femur. Due to the lack of blood flow, the bone dies (osteonecrosis or avascular necrosis) and stops growing. […] Currently, a number of factors have been implicated, including heredity, trauma, endocrine dysfunction, inflammation, nutrition, and altered circulatory hemodynamics. […] The disease is theorized to include the artery of the ligamentum teres femoris being constricted or even blocked too early, not allowing for time when the medial circumflex femoral artery takes over. […] Genetics do not appear to be a determining factor, but a deficiency of blood factors with anticoagulant property used to disperse blood clots may lead to blockages in the vessels supplying the joint. A deficiency of protein C and protein S, which also act as blood anticoagulants, may also exist; if that were the case, their deficiency could cause clot formation in ligamentum teres femoris artery and hinder blood supply to the femoral head. However, no evidence of this has been found; over the years, many theories have been published, but none has stood up to professional research.

• #8 Patient Education | Concord Orthopaedics

  https://www.concordortho.com/patient-resources/patient-education/topic/8de6c8d126950dbbae6601bda872854b

  There is some new evidence that Perthes disease is genetic as a result of a mutation (abnormal change) in the type II collagen (fibers that make up soft tissue structures). Previously there was no known increase in risk for children whose parent had Perthes disease as a child. But this belief may no longer be accurate. […] Other potential biologic factors that may be linked with Perthes disease include low levels of abnormal insulin-like growth factor (IGF-1), low birth weight, and short body length at birth. Exposure to nicotine and other chemicals from tobacco is an important factor recently discovered. Likewise LCP may be triggered by exposure to tobacco if the mother smokes during pregnancy or the child is exposed to second hand smoke during infancy and early childhood. […] There is some evidence that Perthes disease can develop after a single episode of ischemia (lack of blood to the area) no matter what the cause. But the risk goes up with repeated (multiple) episodes of blood loss. Whatever the true cause of ischemia (lack of blood to the area), the result is bone death (called necrosis) of the femoral head. Without a normal blood supply, the bone loses its strength and shape. The loss of bone density and softening of the head result in a misshapen head.

• #9

  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. […] possible association with abnormal clotting factors (Protein S and Protein C deficiencies) 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). […] maternal / passive smoking aggravates.

• #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. […] possible association with abnormal clotting factors (Protein S and Protein C deficiencies) 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). […] maternal / passive smoking aggravates.

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

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

  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%.[2] […] Risk factors for Legg-Calve-Perthes disease include: Ten percent familial (there is a delayed bone age by about 2 years), HIV (Up to 5% of HIV patients have avascular necrosis of the hip), Factor V Leiden and other inherited coagulopathies, Thrombophilias (increased clotting), Hypofibrinolysis (decreased ability to dissolve clots), Secondhand smoke exposure (OR=5), Low socioeconomic status, Birth weight less than 2.5 kg in boys, Short stature[3]

• #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/

  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. […] 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). […] Some authors refer to the injury and initial bone collapse as the cause of LCPD. Others have proposed intravascular thrombosis as a causative mechanism. […] Recently, congenital growth hormone deficiency has also been associated with LCPD. […] Defects in coagulation factors have been considered as one of the possible causes of the impaired supply of blood to the femoral epiphysis.

• #13 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 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. […] 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). […] Some authors refer to the injury and initial bone collapse as the cause of LCPD. Others have proposed intravascular thrombosis as a causative mechanism. […] Recently, congenital growth hormone deficiency has also been associated with LCPD. […] Defects in coagulation factors have been considered as one of the possible causes of the impaired supply of blood to the femoral epiphysis.

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

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

  Regarding race, LCPD occurs with a higher incidence in Caucasians, with the number of cases declining in Asian people and diminishing even more in black people. […] Some studies have shown that there is a correlation between LCPD and exposure to tobacco and wood smoke. […] It has been found that there is a slight correlation between LCPD, growth disturbances and low birth weight. […] Biochemical alterations affect bone development through multiple factors: obesity, abdominal circumference, high density lipoproteins (HDL), tumor necrosis factor alpha (TNF-), interleukins (IL-1 and IL-6), and defects in lipid metabolism. […] 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.

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

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

  Inflammation has an impact on bone modeling; in fact, it has been proposed that heterozygotes of the IL-6 G-174C/G-597 mutation are more likely to develop LCPD. […] Avascularity plays a key role in the etiology of LCPD. […] There are studies that describe families with more than one affected member, which evidences genetic mechanisms may be involved in LCPD, and inheritance patterns, from autosomal recessive to polygenic, have been proposed. […] Since hypercoagulable states could be related to the origin of LCPD, there are studies that relate mutation in factor V Leiden, polymorphisms in prothrombin (PT), and methylenetetrahydrofolate reductase (MTHFR) with the risk of developing LCPD. […] Inflammation is also considered important in the development of LCPD.

• #16 Legg-Calvé-Perthes Disease | SpringerLink

  https://link.springer.com/10.1007/978-3-030-43240-9_124

  Legg-Calv-Perthes disease (LCPD) is a self-limited condition characterized by avascular necrosis (AVN) of the pediatric femoral head. […] Though the precise pathophysiology and etiology of this disease remains a topic of debate, it is thought to be a result of disrupted blood flow to the capital femoral epiphysis. […] The role of coagulation abnormalities in the development of Perthes disease. […] Does thrombophilia play an aetiological role in Legg-Calve-Perthes disease? […] The most severe forms of Perthes disease associated with the homozygous Factor V Leiden mutation. […] Perthes disease and the search for genetic associations: collagen mutations, Gauchers disease and thrombophilia. […] The beta fibrinogen gene G-455-A polymorphism is a risk factor for Legg-Perthes disease. […] The aetiology of Perthes disease. Genetic, epidemiological and growth factors in 310 Edinburgh and Glasgow patients.

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

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

  Inflammation has an impact on bone modeling; in fact, it has been proposed that heterozygotes of the IL-6 G-174C/G-597 mutation are more likely to develop LCPD. […] Avascularity plays a key role in the etiology of LCPD. […] There are studies that describe families with more than one affected member, which evidences genetic mechanisms may be involved in LCPD, and inheritance patterns, from autosomal recessive to polygenic, have been proposed. […] Since hypercoagulable states could be related to the origin of LCPD, there are studies that relate mutation in factor V Leiden, polymorphisms in prothrombin (PT), and methylenetetrahydrofolate reductase (MTHFR) with the risk of developing LCPD. […] Inflammation is also considered important in the development of LCPD.

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

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

  Regarding race, LCPD occurs with a higher incidence in Caucasians, with the number of cases declining in Asian people and diminishing even more in black people. […] Some studies have shown that there is a correlation between LCPD and exposure to tobacco and wood smoke. […] It has been found that there is a slight correlation between LCPD, growth disturbances and low birth weight. […] Biochemical alterations affect bone development through multiple factors: obesity, abdominal circumference, high density lipoproteins (HDL), tumor necrosis factor alpha (TNF-), interleukins (IL-1 and IL-6), and defects in lipid metabolism. […] 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.

• #19 Legg–Calvé–Perthes disease – Wikipedia

  https://en.wikipedia.org/wiki/Legg%E2%80%93Calv%C3%A9%E2%80%93Perthes_disease

  Legg-Calv-Perthes disease (LCPD) is a childhood hip disorder initiated by a disruption of blood flow to the head of the femur. Due to the lack of blood flow, the bone dies (osteonecrosis or avascular necrosis) and stops growing. […] Currently, a number of factors have been implicated, including heredity, trauma, endocrine dysfunction, inflammation, nutrition, and altered circulatory hemodynamics. […] The disease is theorized to include the artery of the ligamentum teres femoris being constricted or even blocked too early, not allowing for time when the medial circumflex femoral artery takes over. […] Genetics do not appear to be a determining factor, but a deficiency of blood factors with anticoagulant property used to disperse blood clots may lead to blockages in the vessels supplying the joint. A deficiency of protein C and protein S, which also act as blood anticoagulants, may also exist; if that were the case, their deficiency could cause clot formation in ligamentum teres femoris artery and hinder blood supply to the femoral head. However, no evidence of this has been found; over the years, many theories have been published, but none has stood up to professional research.

• #20

  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. […] possible association with abnormal clotting factors (Protein S and Protein C deficiencies) 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). […] maternal / passive smoking aggravates.

• #21 Legg-Calvé-Perthes Disease | SpringerLink

  https://link.springer.com/10.1007/978-1-4614-7321-3_124-1

  The beta fibrinogen gene G-455-A polymorphism is a risk factor for Legg-Perthes disease. […] Maternal smoking during pregnancy, other prenatal and perinatal factors, and the risk of Legg-Calve-Perthes disease. […] Smoking and socio-economic status in the etiology and severity of Legg-Calve-Perthes disease.

• #22 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. […] Therefore, it was concluded that the thrombophilic state due to abnormalities of the coagulation system plays a role in the LCPD. […] Variations in genes that code for coagulation factors (F5 and F3) and structural components of bones (COL2A1) might have a role in the etiology of LCPD but, so far, no strong candidate genes underlying increased risk have been identified.

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

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

  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%.[2] […] Risk factors for Legg-Calve-Perthes disease include: Ten percent familial (there is a delayed bone age by about 2 years), HIV (Up to 5% of HIV patients have avascular necrosis of the hip), Factor V Leiden and other inherited coagulopathies, Thrombophilias (increased clotting), Hypofibrinolysis (decreased ability to dissolve clots), Secondhand smoke exposure (OR=5), Low socioeconomic status, Birth weight less than 2.5 kg in boys, Short stature[3]

• #24 Perthes Disease | International Perthes Study Group

  https://perthesdisease.org/perthes/

  Perthes disease is a childhood hip disorder caused by a disruption of blood flow to the ball of the hip joint, or femoral head. The loss of blood flow results in bone death, which is referred to as avascular necrosis or ischemic necrosis of the femoral head. […] We do not know what causes the disruption of blood flow. Perthes disease does not have a strong genetic inheritance, and in fact, only about 5 percent of the patients have a family member with the condition. It also does not appear to be caused by direct hip injury. Some studies have shown an association between Perthes disease and exposure to cigarette smoking, rare blood clotting disorders, hyperactivity and attention deficit disorder, and minor congenital abnormalities like inguinal hernias and undescended testes.

• #25 Legg-Calvé-Perthes disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/legg-calve-perthes-disease/

  Legg-Calvés-Perthes disease is a bone disorder that affects the hips. […] The exact cause of Legg-Calvés-Perthes disease is not known. Some researchers have suggested that the condition is multifactorial, which means it is caused by a combination of genetic, lifestyle, environmental, and metabolic factors. Joint stress, blood clotting abnormalities, malnutrition, obesity, and exposure to cigarette smoke may all contribute to the development of Legg-Calvés-Perthes disease. […] Some cases of Legg-Calvés-Perthes disease were previously thought to be caused by variants (also called mutations) in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen, which is found in connective tissues. Many researchers today, however, do not believe that variants in the COL2A1 gene cause Legg-Calvés-Perthes disease. Studies are investigating the potential causes of Legg-Calvés-Perthes disease, including the role genetics might play in this disorder.

• #26 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. The disease has been reported for more than 100 years, but its etiology has not been elucidated. […] 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. Tissue factor V Leiden mutation and insulin-like growth factor (IGF-1) abnormalities have also been reported in LCPD, but most theories need further confirmation.

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

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

  The cause of the disease is multifactorial involving both genetic, environmental, and nutritional factors. Genetic factors may contribute to the susceptibility of vascular compromise to the capital femoral epiphysis. Polymorphisms in the endothelial nitric oxide synthase gene (eNOS) has been identified in patients with LCPD. Environmental factors include mechanical overload causing repeated subclinical trauma and maternal smoking. Patients often have delayed bone age. LCPD has a higher incidence in groups of lower socioeconomic status, indicating nutritional support may play a role. […] Lack of basic science studies to understand the causative factors, nature of vascular changes, intricate events of bone and cartilage damage, and particle removal and eventual repair. […] 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. […] In addition, antiresorptive and anabolic agents need further investigation to assess their clinical efficacy in the treatment of LCP disease.

• #28 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

  In summary, analyzing global DNA methylation levels and non-coding RNA expression in patients provides the first epigenetic explanation for LCPD etiology. […] Molecular-level changes create a predisposition to disruption of blood supply to the femoral head. For example, COL2A1 mutations weaken the strength of the epiphyseal cartilage matrix, mutations in Factor V Leiden, and deficiencies in Protein-C and Protein-S contribute to thrombophilia, while nitric oxide synthase and IL-6 gene polymorphisms potentially affect endothelial cell function.

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

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

  Inflammation has an impact on bone modeling; in fact, it has been proposed that heterozygotes of the IL-6 G-174C/G-597 mutation are more likely to develop LCPD. […] Avascularity plays a key role in the etiology of LCPD. […] There are studies that describe families with more than one affected member, which evidences genetic mechanisms may be involved in LCPD, and inheritance patterns, from autosomal recessive to polygenic, have been proposed. […] Since hypercoagulable states could be related to the origin of LCPD, there are studies that relate mutation in factor V Leiden, polymorphisms in prothrombin (PT), and methylenetetrahydrofolate reductase (MTHFR) with the risk of developing LCPD. […] Inflammation is also considered important in the development of LCPD.

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

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

  Inflammation has an impact on bone modeling; in fact, it has been proposed that heterozygotes of the IL-6 G-174C/G-597 mutation are more likely to develop LCPD. […] Avascularity plays a key role in the etiology of LCPD. […] There are studies that describe families with more than one affected member, which evidences genetic mechanisms may be involved in LCPD, and inheritance patterns, from autosomal recessive to polygenic, have been proposed. […] Since hypercoagulable states could be related to the origin of LCPD, there are studies that relate mutation in factor V Leiden, polymorphisms in prothrombin (PT), and methylenetetrahydrofolate reductase (MTHFR) with the risk of developing LCPD. […] Inflammation is also considered important in the development of LCPD.

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

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

  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%.[2] […] Risk factors for Legg-Calve-Perthes disease include: Ten percent familial (there is a delayed bone age by about 2 years), HIV (Up to 5% of HIV patients have avascular necrosis of the hip), Factor V Leiden and other inherited coagulopathies, Thrombophilias (increased clotting), Hypofibrinolysis (decreased ability to dissolve clots), Secondhand smoke exposure (OR=5), Low socioeconomic status, Birth weight less than 2.5 kg in boys, Short stature[3]

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

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

  Regarding race, LCPD occurs with a higher incidence in Caucasians, with the number of cases declining in Asian people and diminishing even more in black people. […] Some studies have shown that there is a correlation between LCPD and exposure to tobacco and wood smoke. […] It has been found that there is a slight correlation between LCPD, growth disturbances and low birth weight. […] Biochemical alterations affect bone development through multiple factors: obesity, abdominal circumference, high density lipoproteins (HDL), tumor necrosis factor alpha (TNF-), interleukins (IL-1 and IL-6), and defects in lipid metabolism. […] 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.

• #33 Legg Calve Perthes Disease

  https://www.massgeneral.org/orthopaedics/children/conditions-and-treatments/legg-calve-perthes-disease

  Legg Calv Perthes disease (LCPD) – also known as ischemic (avascular) necrosis of the hip – is a condition characterized by a temporary loss of blood supply to the femoral head (top of the femur). […] Although we do not know a direct cause for Perthes disease, there are several known risk factors. Perthes is much more common in boys (approximately 5:1 male-female ratio). There is also an association of Perthes with ADHD (attention deficit hyperactivity disorder) and in children who are, in general, more active than average (running, jumping, sports, etc). There is also an increased incidence in children who are small for their age (delayed bone age). Finally, there have been some recent studies that connect Perthes disease to prolonged exposure to second-hand smoke. The prolonged inhalation of cigarette smoke can increase the risk of ischemia leading to the avascular necrosis/Perthes disease. […] The condition is found more often in the Asian, Eskimo, and Caucasian population.

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

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

  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%.[2] […] Risk factors for Legg-Calve-Perthes disease include: Ten percent familial (there is a delayed bone age by about 2 years), HIV (Up to 5% of HIV patients have avascular necrosis of the hip), Factor V Leiden and other inherited coagulopathies, Thrombophilias (increased clotting), Hypofibrinolysis (decreased ability to dissolve clots), Secondhand smoke exposure (OR=5), Low socioeconomic status, Birth weight less than 2.5 kg in boys, Short stature[3]

• #35 Legg Calve Perthes Disease (LCP) | Nationwide Children’s Hospital

  https://www.nationwidechildrens.org/conditions/legg-calve-perthes-disease

  This is an idiopathic disease, which means there is no known cause. […] A number of factors have been discussed including: heredity, trauma, endocrine, inflammatory, nutritional, and altered circulatory aspects. […] Risk factors may include: impaired and disproportionate growth, low birth weight, delayed skeletal maturity, short stature, systemic hormonal changes and low economic index. […] This is 4-5 times more likely to occur in males than females. […] This develops when children are between the ages of 4-10, but has been noted in children as young as 2 and as old as 16 year of age. The median age is 6-7. […] Children with Perthes often have delayed bone age. […] Caucasian children are at a higher risk.

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

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

  Regarding race, LCPD occurs with a higher incidence in Caucasians, with the number of cases declining in Asian people and diminishing even more in black people. […] Some studies have shown that there is a correlation between LCPD and exposure to tobacco and wood smoke. […] It has been found that there is a slight correlation between LCPD, growth disturbances and low birth weight. […] Biochemical alterations affect bone development through multiple factors: obesity, abdominal circumference, high density lipoproteins (HDL), tumor necrosis factor alpha (TNF-), interleukins (IL-1 and IL-6), and defects in lipid metabolism. […] 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.

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

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

  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%.[2] […] Risk factors for Legg-Calve-Perthes disease include: Ten percent familial (there is a delayed bone age by about 2 years), HIV (Up to 5% of HIV patients have avascular necrosis of the hip), Factor V Leiden and other inherited coagulopathies, Thrombophilias (increased clotting), Hypofibrinolysis (decreased ability to dissolve clots), Secondhand smoke exposure (OR=5), Low socioeconomic status, Birth weight less than 2.5 kg in boys, Short stature[3]

• #38 Legg-Calve-Perthes Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/826935-overview

  The cause is not known, but children with LCPD have delayed bone age, disproportionate growth, and a mildly shortened stature. LCPD may be idiopathic, or it may result from a slipped capital femoral epiphysis, trauma, steroid use, sickle-cell crisis, toxic synovitis, or congenital dislocation of the hip.

• #39 Legg-Calve-Perthes Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/826935-overview

  The cause is not known, but children with LCPD have delayed bone age, disproportionate growth, and a mildly shortened stature. LCPD may be idiopathic, or it may result from a slipped capital femoral epiphysis, trauma, steroid use, sickle-cell crisis, toxic synovitis, or congenital dislocation of the hip.

• #40 Legg Calve Perthes Disease (LCP) | Nationwide Children’s Hospital

  https://www.nationwidechildrens.org/conditions/legg-calve-perthes-disease

  This is an idiopathic disease, which means there is no known cause. […] A number of factors have been discussed including: heredity, trauma, endocrine, inflammatory, nutritional, and altered circulatory aspects. […] Risk factors may include: impaired and disproportionate growth, low birth weight, delayed skeletal maturity, short stature, systemic hormonal changes and low economic index. […] This is 4-5 times more likely to occur in males than females. […] This develops when children are between the ages of 4-10, but has been noted in children as young as 2 and as old as 16 year of age. The median age is 6-7. […] Children with Perthes often have delayed bone age. […] Caucasian children are at a higher risk.

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

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

  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%.[2] […] Risk factors for Legg-Calve-Perthes disease include: Ten percent familial (there is a delayed bone age by about 2 years), HIV (Up to 5% of HIV patients have avascular necrosis of the hip), Factor V Leiden and other inherited coagulopathies, Thrombophilias (increased clotting), Hypofibrinolysis (decreased ability to dissolve clots), Secondhand smoke exposure (OR=5), Low socioeconomic status, Birth weight less than 2.5 kg in boys, Short stature[3]

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

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

  Regarding race, LCPD occurs with a higher incidence in Caucasians, with the number of cases declining in Asian people and diminishing even more in black people. […] Some studies have shown that there is a correlation between LCPD and exposure to tobacco and wood smoke. […] It has been found that there is a slight correlation between LCPD, growth disturbances and low birth weight. […] Biochemical alterations affect bone development through multiple factors: obesity, abdominal circumference, high density lipoproteins (HDL), tumor necrosis factor alpha (TNF-), interleukins (IL-1 and IL-6), and defects in lipid metabolism. […] 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.

• #43 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 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. […] 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). […] Some authors refer to the injury and initial bone collapse as the cause of LCPD. Others have proposed intravascular thrombosis as a causative mechanism. […] Recently, congenital growth hormone deficiency has also been associated with LCPD. […] Defects in coagulation factors have been considered as one of the possible causes of the impaired supply of blood to the femoral epiphysis.

• #44 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. […] 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. […] A few proposed risk factors include passive exposure to smoke and hyperactivity, although there is no known mechanism linking these risk factors to the development of Legg-Calve-Perthes disease. […] Although the exact cause of Perthes disease is unknown, many environmental and holistic risk factors have been proposed.

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

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

  Regarding race, LCPD occurs with a higher incidence in Caucasians, with the number of cases declining in Asian people and diminishing even more in black people. […] Some studies have shown that there is a correlation between LCPD and exposure to tobacco and wood smoke. […] It has been found that there is a slight correlation between LCPD, growth disturbances and low birth weight. […] Biochemical alterations affect bone development through multiple factors: obesity, abdominal circumference, high density lipoproteins (HDL), tumor necrosis factor alpha (TNF-), interleukins (IL-1 and IL-6), and defects in lipid metabolism. […] 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.

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

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

  Regarding race, LCPD occurs with a higher incidence in Caucasians, with the number of cases declining in Asian people and diminishing even more in black people. […] Some studies have shown that there is a correlation between LCPD and exposure to tobacco and wood smoke. […] It has been found that there is a slight correlation between LCPD, growth disturbances and low birth weight. […] Biochemical alterations affect bone development through multiple factors: obesity, abdominal circumference, high density lipoproteins (HDL), tumor necrosis factor alpha (TNF-), interleukins (IL-1 and IL-6), and defects in lipid metabolism. […] 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.

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

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

  Regarding race, LCPD occurs with a higher incidence in Caucasians, with the number of cases declining in Asian people and diminishing even more in black people. […] Some studies have shown that there is a correlation between LCPD and exposure to tobacco and wood smoke. […] It has been found that there is a slight correlation between LCPD, growth disturbances and low birth weight. […] Biochemical alterations affect bone development through multiple factors: obesity, abdominal circumference, high density lipoproteins (HDL), tumor necrosis factor alpha (TNF-), interleukins (IL-1 and IL-6), and defects in lipid metabolism. […] 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.

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

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

  Regarding race, LCPD occurs with a higher incidence in Caucasians, with the number of cases declining in Asian people and diminishing even more in black people. […] Some studies have shown that there is a correlation between LCPD and exposure to tobacco and wood smoke. […] It has been found that there is a slight correlation between LCPD, growth disturbances and low birth weight. […] Biochemical alterations affect bone development through multiple factors: obesity, abdominal circumference, high density lipoproteins (HDL), tumor necrosis factor alpha (TNF-), interleukins (IL-1 and IL-6), and defects in lipid metabolism. […] 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.

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

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

  Regarding race, LCPD occurs with a higher incidence in Caucasians, with the number of cases declining in Asian people and diminishing even more in black people. […] Some studies have shown that there is a correlation between LCPD and exposure to tobacco and wood smoke. […] It has been found that there is a slight correlation between LCPD, growth disturbances and low birth weight. […] Biochemical alterations affect bone development through multiple factors: obesity, abdominal circumference, high density lipoproteins (HDL), tumor necrosis factor alpha (TNF-), interleukins (IL-1 and IL-6), and defects in lipid metabolism. […] 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.

• #50 Symptoms, Causes and Treatment of Perthes Disease | HSS

  https://www.hss.edu/conditions_legg-calve-perthes-disease-overview.asp

  Legg-Calve-Perthes disease is widely believed to be caused by idiopathic avascular necrosis of the femoral head. […] Neither scientists nor physicians understand why the blood supply to the femoral head becomes compromised in such cases. […] Attention deficit disorder and coagulopathies have been associated with Perthes.

• #51 Legg Calve Perthes Disease

  https://www.massgeneral.org/orthopaedics/children/conditions-and-treatments/legg-calve-perthes-disease

  Legg Calv Perthes disease (LCPD) – also known as ischemic (avascular) necrosis of the hip – is a condition characterized by a temporary loss of blood supply to the femoral head (top of the femur). […] Although we do not know a direct cause for Perthes disease, there are several known risk factors. Perthes is much more common in boys (approximately 5:1 male-female ratio). There is also an association of Perthes with ADHD (attention deficit hyperactivity disorder) and in children who are, in general, more active than average (running, jumping, sports, etc). There is also an increased incidence in children who are small for their age (delayed bone age). Finally, there have been some recent studies that connect Perthes disease to prolonged exposure to second-hand smoke. The prolonged inhalation of cigarette smoke can increase the risk of ischemia leading to the avascular necrosis/Perthes disease. […] The condition is found more often in the Asian, Eskimo, and Caucasian population.

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

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

  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%.[2] […] Risk factors for Legg-Calve-Perthes disease include: Ten percent familial (there is a delayed bone age by about 2 years), HIV (Up to 5% of HIV patients have avascular necrosis of the hip), Factor V Leiden and other inherited coagulopathies, Thrombophilias (increased clotting), Hypofibrinolysis (decreased ability to dissolve clots), Secondhand smoke exposure (OR=5), Low socioeconomic status, Birth weight less than 2.5 kg in boys, Short stature[3]

• #53 Legg-Calvé-Perthes disease – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/legg-calve-perthes-disease/

  Idiopathic disease […] Multiple factors might promote the development and progress of the condition, including: […] Repetitive microtrauma (e.g., due to child’s hyperactivity) […] Bleeding disorders (e.g., excess factor VII, factor V Leiden, protein S deficiency) […] Genetic factors (e.g., possible mutations in COL2A1 gene) […] Environmental factors (e.g., maternal smoking, secondhand smoke exposure)

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

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

  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%.[2] […] Risk factors for Legg-Calve-Perthes disease include: Ten percent familial (there is a delayed bone age by about 2 years), HIV (Up to 5% of HIV patients have avascular necrosis of the hip), Factor V Leiden and other inherited coagulopathies, Thrombophilias (increased clotting), Hypofibrinolysis (decreased ability to dissolve clots), Secondhand smoke exposure (OR=5), Low socioeconomic status, Birth weight less than 2.5 kg in boys, Short stature[3]

• #55 Legg-Calve-Perthes Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/826935-overview

  The cause is not known, but children with LCPD have delayed bone age, disproportionate growth, and a mildly shortened stature. LCPD may be idiopathic, or it may result from a slipped capital femoral epiphysis, trauma, steroid use, sickle-cell crisis, toxic synovitis, or congenital dislocation of the hip.

• #56 Legg-Calve-Perthes Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/826935-overview

  The cause is not known, but children with LCPD have delayed bone age, disproportionate growth, and a mildly shortened stature. LCPD may be idiopathic, or it may result from a slipped capital femoral epiphysis, trauma, steroid use, sickle-cell crisis, toxic synovitis, or congenital dislocation of the hip.

• #57 Perthes’ Disease. Symptoms of perthes’? Causes, effects

  https://patient.info/doctor/perthes-disease-pro

  This is a self-limiting hip disorder caused by varying degrees of ischaemia and subsequent necrosis of the femoral head. […] The primary event is avascular necrosis of the femoral epiphysis, which results in delayed ossific nucleus. […] Transient synovitis (this was thought to lead to Perthes’ disease; however, it is now believed there is no causal relationship).

• #58 Legg-Calve-Perthes Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/826935-overview

  The cause is not known, but children with LCPD have delayed bone age, disproportionate growth, and a mildly shortened stature. LCPD may be idiopathic, or it may result from a slipped capital femoral epiphysis, trauma, steroid use, sickle-cell crisis, toxic synovitis, or congenital dislocation of the hip.

• #59 Legg-Calve-Perthes Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/826935-overview

  The cause is not known, but children with LCPD have delayed bone age, disproportionate growth, and a mildly shortened stature. LCPD may be idiopathic, or it may result from a slipped capital femoral epiphysis, trauma, steroid use, sickle-cell crisis, toxic synovitis, or congenital dislocation of the hip.

• #60 Perthes Disease | International Perthes Study Group

  https://perthesdisease.org/perthes/

  Perthes disease is a childhood hip disorder caused by a disruption of blood flow to the ball of the hip joint, or femoral head. The loss of blood flow results in bone death, which is referred to as avascular necrosis or ischemic necrosis of the femoral head. […] We do not know what causes the disruption of blood flow. Perthes disease does not have a strong genetic inheritance, and in fact, only about 5 percent of the patients have a family member with the condition. It also does not appear to be caused by direct hip injury. Some studies have shown an association between Perthes disease and exposure to cigarette smoking, rare blood clotting disorders, hyperactivity and attention deficit disorder, and minor congenital abnormalities like inguinal hernias and undescended testes.

• #61 Legg-Calvé-Perthes Disease in Children | Cedars-Sinai

  https://www.cedars-sinai.org/health-library/diseases-and-conditions—pediatrics/l/legg-calve-perthes-disease.html

  Legg-Calv-Perthes disease (or Perthes disease) is a rare hip condition that affects children. […] The cause of Legg-Calv-Perthes disease is unknown. It is 4 to 5 times more likely to happen in boys than girls. It typically occurs in children ages 3 to 12. The majority of cases affect only one hip. […] The more severe the case, the greater the likelihood that your child may have limited hip motion, differences in leg lengths, and other hip problems in adulthood.

• #62 Legg-Calvé-Perthes disease | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/legg-calve-perthes-disease

  Legg-Calv-Perthes disease (or Perthes disease) is a rare condition in children in which the ball-shaped head of the thigh bone, referred to as the femoral head, loses its blood supply. […] The cause of Legg-Calv-Perthes disease is unknown. It is four times more likely to occur in boys than girls and is uncommon in African-Americans.

• #63 Legg Calve Perthes Disease (LCP) | Nationwide Children’s Hospital

  https://www.nationwidechildrens.org/conditions/legg-calve-perthes-disease

  This is an idiopathic disease, which means there is no known cause. […] A number of factors have been discussed including: heredity, trauma, endocrine, inflammatory, nutritional, and altered circulatory aspects. […] Risk factors may include: impaired and disproportionate growth, low birth weight, delayed skeletal maturity, short stature, systemic hormonal changes and low economic index. […] This is 4-5 times more likely to occur in males than females. […] This develops when children are between the ages of 4-10, but has been noted in children as young as 2 and as old as 16 year of age. The median age is 6-7. […] Children with Perthes often have delayed bone age. […] Caucasian children are at a higher risk.

• #64 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. The disease has been reported for more than 100 years, but its etiology has not been elucidated. […] 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. Tissue factor V Leiden mutation and insulin-like growth factor (IGF-1) abnormalities have also been reported in LCPD, but most theories need further confirmation.

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

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

  Regarding race, LCPD occurs with a higher incidence in Caucasians, with the number of cases declining in Asian people and diminishing even more in black people. […] Some studies have shown that there is a correlation between LCPD and exposure to tobacco and wood smoke. […] It has been found that there is a slight correlation between LCPD, growth disturbances and low birth weight. […] Biochemical alterations affect bone development through multiple factors: obesity, abdominal circumference, high density lipoproteins (HDL), tumor necrosis factor alpha (TNF-), interleukins (IL-1 and IL-6), and defects in lipid metabolism. […] 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.

• #66 Legg Calve Perthes Disease

  https://www.massgeneral.org/orthopaedics/children/conditions-and-treatments/legg-calve-perthes-disease

  Legg Calv Perthes disease (LCPD) – also known as ischemic (avascular) necrosis of the hip – is a condition characterized by a temporary loss of blood supply to the femoral head (top of the femur). […] Although we do not know a direct cause for Perthes disease, there are several known risk factors. Perthes is much more common in boys (approximately 5:1 male-female ratio). There is also an association of Perthes with ADHD (attention deficit hyperactivity disorder) and in children who are, in general, more active than average (running, jumping, sports, etc). There is also an increased incidence in children who are small for their age (delayed bone age). Finally, there have been some recent studies that connect Perthes disease to prolonged exposure to second-hand smoke. The prolonged inhalation of cigarette smoke can increase the risk of ischemia leading to the avascular necrosis/Perthes disease. […] The condition is found more often in the Asian, Eskimo, and Caucasian population.

• #67 Legg-Calvé-Perthes Disease in Children | Cedars-Sinai

  https://www.cedars-sinai.org/health-library/diseases-and-conditions—pediatrics/l/legg-calve-perthes-disease.html

  Legg-Calv-Perthes disease (or Perthes disease) is a rare hip condition that affects children. […] The cause of Legg-Calv-Perthes disease is unknown. It is 4 to 5 times more likely to happen in boys than girls. It typically occurs in children ages 3 to 12. The majority of cases affect only one hip. […] The more severe the case, the greater the likelihood that your child may have limited hip motion, differences in leg lengths, and other hip problems in adulthood.

• #68 What is Legg-Calvé-Perthes Disease?

  https://www.gillettechildrens.org/conditions-care/legg-calve-perthes-disease/what-is-legg-calve-perthes-disease

  Legg-Calv-Perthes disease (also known as simply Perthes) is a condition in which the blood supply to the hip bone is temporarily interrupted, causing the bone in the hip to deteriorate. […] The cause of Perthes is unknown. The condition usually occurs in children from 4 to 8 years of age, but can occur between ages 18 months to 14 years. […] The disease often develops in children who are very physically active. In most children, the condition typically occurs in one of their hips, and only approximately 10 15% of children have both of their hips affected. […] Perthes is rare, with an incidence of roughly 3 to 6 per 100,000 children in North America. The condition affects boys four to five times more than girls.

• #69 Legg-Calve-Perthes Disease | Pediatric Orthopaedic Society of North America (POSNA)

  https://posna.org/physician-education/study-guide/legg-calve-perthes-disease

  Legg-Calve-Perthes disease is a childhood femoral head ischemia of unknown etiology that may lead to permanent hip deformity. […] Presence of synchronous, relatively symmetric bilateral head involvement should prompt the search for other etiologies. […] The disease follows distinct radiographic stages described by Waldenstrm: 1) initial – with ischemia-induced sclerosis; 2) fragmentation – when absorption, fibrovascular invasion, physeal changes, and cartilaginous metaplasia lend a lytic appearance to the epiphysis and metaphysis, with variable collapse; 3) re-ossification – when the fibrovascular and cartilage islands are replaced by bone. […] On average, the stages last five, nine, and 19 months, respectively. […] There is some association with history of smoke exposure. […] The type of treatment recommended is based on patients age, stage of disease, and severity of involvement (radiographic class).

• #70 Legg-Calve-Perthes-Disease Scottsdale AZ | Hip Disorder Treatment Phoenix AZ

  https://www.lkaplanmd.com/legg-calve-perthes-disease-knee-hip-replacement-scottsdale-phoenix-az.html

  The cause of Legg-Calve-Perthes disease is not clearly known. It may occur due to inadequate blood supply to the ball of the hip joint (femoral head), which leads to death of the bone. […] Over the course of several months, the blood supply returns to the bone tissue and new bone cells gradually replace the dead bone over 2 – 3 years.

• #71 Legg-Calve-Perthes disease

  https://www.mymlc.com/health-information/diseases-and-conditions/l/legg-calve-perthes-disease2/

  Legg-Calve-Perthes disease occurs when too little blood is supplied to the ball portion of the hip joint (femoral head). Without enough blood, this bone becomes weak and fractures easily. The cause of the temporary reduction in blood flow to the femoral head remains unknown. […] The complete process of bone death, fracture and renewal can take several years.

• #72 Legg-Calve-Perthes or 'Perthes’ disease | Doctor – PMM

  https://www.pmmonline.org/doctor/limping-child/key-conditions/hip-disorders/legg-calve-perthes-or-perthes-disease/

  In Perthes disease, the blood supply to the femoral epiphysis is interrupted, leading to avascular necrosis. The cause is unknown. […] It is important to bear in mind that Perthes disease extends over several years (4-6 years) and that it is the shape of the femoral head (round-good, flat-bad) at the final stage that decides the long-term prognosis.

• #73 Legg-Calve-Perthes disease: etiology, pathogenesis, and biology – PubMed

  https://pubmed.ncbi.nlm.nih.gov/21857428/

  Legg-Calve-Perthes disease is a complex pediatric hip disorder with many uncertainties. Various theories on its etiology have been proposed but none have been validated conclusively. […] Through experimental studies, however, some insight into the pathogenesis of a femoral head deformity after ischemic necrosis has been gained. These studies reveal that mechanical and biological factors contribute to the development of the femoral head deformity. Better understanding of the pathobiology of Legg-Calve-Perthes disease will lead to the development of more effective treatments, which are able to specifically target the pathogenic processes.

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

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

  LeggCalvPerthes Disease (LCPD) is a necrosis of the femoral head which affects the range of motion of the hips. Its incidence is variable, ranging from 0.4/100,000 to 29.0/ 100,000 children. […] Although LCPD was first described in the beginning of the past century and has been studied for more than 100 years, limited is known about its etiology. […] This review suggests that LCPD has a multifactorial etiology where environmental, metabolic and genetic agents could be involved. […] The cause of LCPD is unknown. Different etiologies have been proposed; nevertheless, LCPD may be caused by multiple etiologic factors that share a common final pathogenic pathway. A new perspective is that LCPD is a multifactorial disease caused by a combination of environmental, metabolic and genetic factors.

• #75 Legg-Calve-Perthes disease: etiology, pathogenesis, and biology – PubMed

  https://pubmed.ncbi.nlm.nih.gov/21857428/

  Legg-Calve-Perthes disease is a complex pediatric hip disorder with many uncertainties. Various theories on its etiology have been proposed but none have been validated conclusively. […] Through experimental studies, however, some insight into the pathogenesis of a femoral head deformity after ischemic necrosis has been gained. These studies reveal that mechanical and biological factors contribute to the development of the femoral head deformity. Better understanding of the pathobiology of Legg-Calve-Perthes disease will lead to the development of more effective treatments, which are able to specifically target the pathogenic processes.

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