AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Intervention
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Intervention
• Multimedia
• References

Background

Avascular necrosis of the femoral head (AVN) is an increasingly common cause of musculoskeletal disability as well as a major diagnostic and therapeutic challenge. Although initially patients are asymptomatic, AVN usually progresses to joint destruction, requiring total hip replacement (THR) in individuals, usually before the fifth decade. It is estimated that almost 10% of the nearly 500,000 THRs performed each year in the United States are intended to treat AVN at a cost of more than 1 billion dollars, approximately one fourth of the national budget for THR.

Although treatment has been facilitated using a widely accepted international classification system, effective earlier diagnosis using MRI, and more aggressive surgical management, no universally satisfactory therapy has been developed, even for early disease.

Since joint preservation measures have a much better prognosis when the diagnosis of AVN is made early in the course of the disease and since the results of joint replacement therapy are poorer in younger age groups, diagnosing AVN as early as possible is critical to prevent or delay progression of the disease.

AVN is characterized by areas of dead trabecular bone and marrow extending to involve the subchondral plate. The anterolateral aspect of the femoral head, the principal weightbearing region, typically is involved, but no region of the femoral head is necessarily spared. In the adult, the involved segment usually never fully revascularizes and, once detected radiographically, collapse of the femoral head usually occurs later.

Konig first described the condition, then termed osteochondritis dissecans, in 1888. In 1925, Haenish described the first case of idiopathic ischemic necrosis of the femoral head in an adult. In 1940, arterial occlusion was postulated as the cause of the necrosis. AVN following steroid therapy was described first by Pietrograndi in 1957.

AVN represents an inability to supply adequate oxygen to underlying bone. AVN is extremely rare in healthy individuals.

AVN only occurs in fatty marrow, which contains a sparse vascular supply. In contrast, hematopoietic marrow has a rich blood supply.

The femoral head is the most vulnerable site for development of AVN. The site of necrosis is usually immediately below the weightbearing articular surface of the bone, the anterolateral aspect of the femoral head. This is the site of greatest mechanical stress.

Elderly persons are at decreased risk for developing AVN. Fat cells become smaller in this age group. The space between fat cells fills with a loose reticulum and mucoid fluid, which are resistant to AVN. This is termed gelatinous marrow and, even in the presence of increased intramedullary pressure, intersitial fluid is able to escape into the blood vessels leaving the spaces free to absorb additional fluid.

Nontraumatic AVN is commonly bilateral and occurs in a younger population.

Nontraumatic bilateral AVN usually occurs at different times and progresses at different rates in each individual hip.

Incidence of AVN is increasing. The causes include greater use of exogenous steroids and an increase in trauma.

Etiology

Pathologic changes leading to AVN are initiated in two broad categories of anatomic regions, intravascular and extravascular factors.

Intravascular factors

Extraosseous vascular factors - Arterial factors

Arterial factors are believed to be the most important mechanism for the development of AVN. The femoral head is at increased risk for developing AVN, partly because the blood supply is an end-organ system with poor collateral development. Trauma to the hip may lead to contusion or mechanical interruption to the lateral retinacular vessels, the main blood supply of the femoral head and neck. In a large group of patients, arteriography demonstrated stenosing arteritis and atherosclerotic disease of the lateral retinacular vessels, which may be an important consideration in older patients.

Vasculitis, as seen in Raynaud disease, or vasospasm, as seen in decompression sickness, can interfere with extraosseous circulation. Extraosseous interruption of the lateral epiphyseal and medial femoral circumflex arteries has been demonstrated in early adult AVN and Perthes disease by superselective angiography.

Intraosseous vascular factors - Arterial

The primary etiology appears to be circulating microemboli that block the microcirculation of the femoral head. Such conditions can occur in sickle cell disease (SCD), fat embolization, or air embolization from dysbaric phenomena. Vascular obstruction to the microcirculation can be caused by fat emboli, related to hyperlipidemia associated with alcoholism, steroid therapy, SCD, and nitrogen bubbles in decompression sickness.

Intraosseous vascular factors - Venous

Conditions such as Caisson disease and SCD have a strong tendency to involve the venous side of the circulation, reducing venous outflow and causing stasis. Enlargement of intramedullary fat cells or fat-loading osteocytes causes them to expand and may be the most significant factor leading to obstruction of venous drainage. Intraosseous venography in patients with AVN demonstrated widespread abnormalities in the venous drainage system, indicating that venous circulation participates in and contributes to progression of this disorder.

The ability to decompress the marrow space depends on regional anatomic structures, especially vascular outflow and bony architecture. The femoral head is at an anatomic disadvantage for decompression because it is a large sphere perched on a narrow metaphyseal neck. Relatively few venous channels permeating the bony cortex are directly available for decompression. An increase in pressure within this large area must be funneled through the narrow metaphyseal neck for decompression, which is a situation analogous to rush-hour traffic feeding onto a single-lane bridge.

Extravascular factors

Intraosseous factors

The bone system within the subchondral region of the femoral head is enclosed within a rigid shell of cortical bone. Such a system is particularly sensitive to increases in pressure resulting in a compartment syndrome. Ficat et al demonstrated increased bone marrow pressure in the femoral necks of a large number of patients with AVN. The first effects of raised pressure are on the sinusoids and the small marrow capillaries, then on the venous outflow. Reflex spasm can even block nutrient vessels before they enter the cortex.

Fat cells, through hypertrophy resulting from steroid administration, and abnormal cells, such as Gaucher cells and inflammatory cells, can encroach on intraosseous capillaries, reducing intramedullary circulation and contributing to compartment syndrome. Blood flow normally is poorer in fatty marrow. The risk of AVN is increased when the volume of fatty marrow increases at the expense of hematopoietic marrow. This situation is present in normal marrow conversion in the adult and in conditions that increase the size and volume of the marrow, as in steroid administration. Transmitted pressure in the weightbearing region of the femur compresses capillary circulation, which is already compromised by increased intraosseous pressure.

Repeated microfractures in the weightbearing segment of the femur may cause multiple vascular lesions resulting in ischemia within fragile and poorly repaired bone.

In cellular cytotoxic factors, such as alcoholism and steroid-related AVN, the cause may result from a direct toxic metabolic effect on osteogenic cells.

The subchondral weightbearing area of the femoral head is at a special disadvantage when decompression is needed. Greater amounts of more tightly packed cancellous bone are present in this region due to the mechanical requirements of weightbearing, creating a baffle effect and further restricting ability to decompress the marrow space in comparison with the more open adjacent subchondral areas.

Trabecular deformation, which normally occurs during weightbearing, also compresses the marrow space to some degree and should result in a localized temporary increase in intraosseous pressure. This situation may be aggravated further by the morphologic profile of reduced trabecular bone, thickened osteoid seams, and indolent calcification dynamics noted in specimens from iliac bone biopsies performed in patients with abnormal renal function and AVN.

In some instances of idiopathic osteonecrosis, these changes have been accompanied by decreased concentrations of 1,25 dihydroxyvitamin D3. Such findings suggest a possible quantitative or qualitative deficiency in the bone architecture, which undoubtedly potentiates the altered pressure effects of deformation. In either event, increased intraosseous pressure tends to remain concentrated in this area because of the tightly structured architecture. This, coupled with a situation in which intraosseous pressure already is elevated, can transform an area of bone that is ischemic and marginally perfused into an area of functional anoxia with resulting infarction.

Capsular factors

Disease processes within the hip joint that produce effusions, such as trauma, infection, and arthritis, may affect the blood supply to the epiphysis adversely. The mechanism involves tamponade of the lateral epiphyseal vessels (LEVs; the primary blood supply to the epiphysis), which are located within the synovial membrane, through increased intracapsular pressure.

Pathophysiology

Summary of pathophysiologic factors

Although some authors feel that the cause of AVN most likely is related to thrombosis or embolization of smaller arteries of the femoral head by lipid droplets, abnormal red blood cells (as in SCD), or nitrogen bubbles from Caisson disease, others feel that vasculopathy with structural damage to the arterial or venous walls from vasculitis, radiation necrosis, or release of vasoactive substances (as in Gaucher disease) is the cause. Still others feel that increased intraosseous pressure from enlargement of intramedullary fat cells or osteocytes is a factor.

The consensus indicates that the cause is multifactorial and that it is better to deal with the disease as the end result of a number of different factors with the final common pathway resulting in bone death and collapse of the femoral head.

The final common pathway may represent intravascular coagulation with fibrin-platelet thrombosis beginning in the vulnerable subchondral microcirculation (capillary and sinusoidal beds) resulting in vasoconstriction and impaired fibrinolysis (reperfusion of necrotic vessels with intramedullary hemorrhages) and infarction.

Intravascular thrombosis occurs throughout the body on a smaller scale but lysis occurs through the fibrinolytic system. A thrombotic process of short duration can be lysed rapidly with preservation of the original thrombosed vessel. Conversely, a thrombotic process of prolonged duration or of a repeated nature may damage the vessel significantly, resulting in fibrosis and obliteration of the vessel lumen. In this situation, the vascular supply must be restored, either through the process of recanalization or through neovascularization. Recanalization can occur within minutes to days with little morbidity but can be halted by further thrombotic episodes or subsequent trauma. Neovascularization requires months to years to complete.

Sequelae of AVN

Minimal disease: If the vascular area is small and not adjacent to an articular surface, the patient may be asymptomatic and may heal spontaneously, and the disease may remain undetected or be discovered incidentally during workup for other conditions.

More severe disease: Once AVN develops, repair begins at the interface between viable and necrotic bone. Ineffective resorption of dead bone within the necrotic focus is the rule. Dead bone is reabsorbed only partially. Reactive and reparative bone is laid down on dead trabeculae resulting in a sclerotic margin of thickened trabeculae within an advancing front of hyperemia, inflammation, bone resorption, and fibrosis. The incomplete resorption of dead bone results in a mixed sclerotic and cystic appearance on radiographs. Necrosis and repair are ongoing in various stages of evolution within a single lesion.

Mechanical failure: Mechanical failure of trabecular bone at the interface between dead and viable bone may exacerbate AVN. In the subchondral region, such microfractures do not heal because they occur within an area of dead bone. Progression of the microfractures results in a diffuse subchondral fracture, seen radiographically as the crescent sign (see Image 9). Following subchondral fracture and progressive weightbearing, collapse of the articular cartilage occurs (see Image 8, Image 20, Images 25-26). Continued fracture, necrosis, and further weightbearing can progress to degenerative joint disease (DJD) and joint dissolution.

Conditions associated with AVN

Trauma

Trauma is the most common cause of AVN. AVN can occur within 8 hours after traumatic disruption of the blood supply. The superior retinacular vessels and the nutrient artery can be damaged as they enter the femur. The artery of the ligamentum teres (ALT) also may be damaged. Intracapsular hematoma increases intracapsular pressure, which can cause tamponade of the vessels within the joint capsule.

Intertrochanteric and extracapsular fractures of the femur rarely develop AVN. Following hip dislocation, circulation is interrupted because of tears of the ligamentum teres, tearing the ALT. Tearing of the joint capsule compromises the vessels within the capsular reflections. AVN following subcapital fractures of the femur can develop as late as 10 years after fracture.

Alcoholism

Alcohol may have a toxic effect on osteogenic cells. The direct toxic effect of alcohol results in fat deposition in the liver. Livers with fat deposits are a constant source of low-grade asymptomatic fat emboli. Intraosseous fat emboli become hydrolyzed to free fatty acids, which cause endothelial damage. Alcohol intake exceeding 40 mL per week increases the risk of AVN more than 11 times compared to the risk in nondrinkers. A clear dose-response relationship exists.

Steroid use

Six possible mechanisms may be present.

• Occlusion of small vessels occurs related to fat emboli from the liver.
• Increased intraosseous pressure results from a steroid-related increase in the size of the intramedullary fat cells without an equivalent compensatory loss of trabecular and cortical bone.
• Fat emboli become hydrolyzed to free fatty acids, which are toxic to vascular endothelium, causing intravascular coagulation.
• Angiogenesis is inhibited by a reduction of proteolytic activity by the synthesis of polyclonal antithyroid hormone receptor alpha-1 antibody (PA).
• A direct toxic effect occurs on osteogenic cells.
• Steroid use causes conversion of hematopoietic marrow to fatty marrow, a prerequisite for the development of AVN. The conversion may be related to steroid-induced reduced blood flow.

Steroid exposure threshold is approximately 2000 mg of prednisone administered continuously. However, AVN has been described following lower doses. The risk of AVN is greater risk in patients treated for a short duration (6 wk) with high doses (>20 mg). However, the risk of AVN in low-dose steroid therapy is controversial. Studies both link such therapy to the disease and refute the role of such treatment. High doses of steroids administered within a relatively short period are more of a causative factor than cumulative dose or duration of therapy.

AVN can occur up to 3 years following cessation of therapy. Steroid-induced AVN is more severe than AVN caused by other conditions because underlying demineralization and accelerated osteolysis place the weightbearing surface of the femoral head at increased risk of collapse.

Individuals with systemic lupus erythematosus (SLE) and renal allograft recipients treated with steroids have the highest incidence of AVN. In renal transplantation, a high association exists between AVN and prednisone doses greater than 100 mg/d within the first month following transplantation. AVN is uncommon in transplant recipients taking less than 100 mg/d. Risk is increased of underlying bone changes associated with chronic renal disease, such as hypophosphatemia. Reducing renal bone disease with better dialysis (increasing ionized calcium in the dialysate) and medical management significantly reduces the incidence of AVN. A delay in diagnosis may occur because of pain reduction provided by concurrent administration of steroids.

In systemic lupus erythematosus, AVN is the dominant orthopedic problem in patients with SLE. Patients with SLE with vasculitis and Raynaud syndrome are at higher risk for developing AVN. Patients usually are younger and have more active disease with multiple organ involvement.

Decompression sickness (Caisson disease)

Workers in underwater enclosures requiring compressed air to prevent water seepage are at risk. AVN occurs as a result of exposure to pressure greater than 17 lb per square inch. These infarcts tend to be large. Undersea divers are at risk. Key risk factors are the depth of the dive, the number of dives, uncontrolled decompression, and low oxygen concentrations. The presence of intravascular bubbles of nitrogen obstructs capillaries. Extravascular nitrogen within the fatty marrow, encased within the bone, compresses intramedullary vessels. Arteriolar spasm also may occur. Fat cells have a 5-fold ability to absorb dissolved nitrogen. Such absorption increases their volume within the nonexpandable confines of the bony trabeculae and cortex, increasing intraosseous marrow pressure and causing venous stasis.

Metastatic disease

Metastatic cells can pack the marrow, resulting in increased intramedullary pressure obstructing the intramedullary vessels. Patients are at higher risk if they are receiving steroid therapy and/or are undergoing local radiation therapy to the hip.

Pancreatic disease

The release of lipolytic enzymes into the bloodstream results in breakdown of the fat within the marrow cells into free fatty acids, which are toxic to endothelium, causing intravascular coagulation. Upon entering the portal venous radicals in patients with pancreatitis, pancreatic enzymes can cause release of intracellular fat from fat-laden hepatic cells.

Hemoglobinopathies (SCD, thalassemia, hemoglobin C disease, hemoglobin D disease, hemoglobin E disease)

Hemoglobinopathies are the principal cause of AVN in African countries such as the Democratic Republic of the Congo (formerly Zaire). Infarcts in hemoglobinopathies tend to be large. AVN only occurs when a sickle gene is present to cause the sickling phenomena. Sickling of abnormal red blood cells occurs in intramedullary capillaries and venules, causing hyperviscosity and vascular occlusion.

Bone marrow hyperplasia resulting from chronic anemia may pack the marrow, placing it at increased risk for developing AVN from elevated intramedullary pressure. Sites of AVN are susceptible to osteomyelitis caused by Salmonella infection. See US frequency. AVN may be more common in patients with the sickle trait and sickle-thalassemia than in patients who are homozygous for the sickle gene because the latter do not live long enough to demonstrate the changes.

Gaucher disease

Gaucher disease is a metabolic disorder consisting of a deficiency of the enzyme b-glucosidase, which normally catalyzes the removal of glucose from glucocerebroside. Glucocerebroside accumulates in the reticuloendothelial cells within the bone marrow, resulting in packing of marrow, compression of interosseous sinusoids, and elevation of interosseous pressure. Infarcts tend to be large.

Dialysis

Elevated levels of parathormone may cause increased subchondral bone turnover with replacement by disorganized bone matrix unable to support normal weightbearing, resulting in microfractures and increased intramedullary pressure.

Irradiation

Fibrosis and endothelial proliferation resulting from radiation-induced arteritis cause underlying vascular compromise. Patients with metastatic lymphoma or carcinoma to the femoral head who are treated with steroids and chemotherapy are at increased risk of developing AVN. AVN occurs with doses exceeding 30 Gy.

Hemophilia

Repeated microhemorrhages within the confines of the marrow result in increased intramedullary pressure. Capsular distension from hemorrhage may compress the retinacular vessels within the synovial capsule.

Hypercoagulable states - Inherited disorders

Deficiencies occur of specific protein inhibitors of the coagulation cascade (protein C, protein S, and structural abnormalities of factor V [resistance to activated protein C]). Protein S is a vitamin K-dependent antithrombin plasma protein that serves as a cofactor for another antithrombotic plasma protein, protein C. Once activated, protein C inhibits the coagulation cascade by enzymatic cleavage of the activated forms of clotting factors V and VII.

Disorders of the fibrinolytic system occur, ie, impaired release of tissue plasminogen activator activity and increased levels of lipoprotein A.

Hyperfibrinogenemia produces a hypercoagulable state and is associated with enhanced erythrocyte aggregation and hyperviscosity resulting in a reduction of blood flow and ischemia. Hyperfibrinogenemia is seen in patients with hyperlipoproteinemia (types II and IV), patients who smoke, have diabetes, and use oral contraceptives. Along with hereditary thrombophilia, hyperfibrinogenemia may decrease the threshold for developing AVN in alcoholism and steroid administration.

Hypercoagulable states - Acquired disorders

When superimposed on underlying hereditable disorders, acquired disorders increase the likelihood of vascular thrombosis synergistically.

• Legg-Calvé-Perthes (LCP) disease is the most common cause of AVN in children.
  
  
  • The time of onset ranges from age 3-10 years, with the highest incidence occurring from age 6-8 years. The greatest incidence is in Japanese, Mongolian, Eskimo, and Central European children, with a low incidence in blacks and American Indians.
  • The vascular anatomy of the proximal femur is in a transitional stage of development in children aged 4-7 years, making the blood supply to the femoral head especially vulnerable. The artery of the ligamentum teres does not penetrate the epiphysis of the femoral head until age 9 or 10 years. The epiphyseal growth plate prevents communication between the blood supply of the epiphysis and metaphysis, thus the femoral head is at increased risk for developing AVN, even from innocuous events such as minor trauma.
  • Venous tamponade also may contribute to developing AVN. Nonspecific synovitis may elevate intracapsular pressure sufficiently to obstruct venous outflow. In adults, epiphyseal venous drainage can go into the metaphysis and may protect the femoral head.
• Slipped capital femoral epiphysis
  
  
  • Epiphyseal dislocation results in superolateral displacement and external rotation of the femoral metaphysis, twisting and kinking the lateral epiphyseal vessels resulting in compromise to the blood flow to the epiphysis. Dislocation tends to occur late in the terminal stage of renal failure.
  • Epiphyseal dislocation can occur in hypothyroidism, obesity, growth hormone administration, and radiation therapy.
  • When related to HIV infection, multifactorial etiologies probably are involved. Hypertriglyceridemia, as seen in AIDS wasting, may be potentiated by steroid use, either chronically from megestrol therapy for wasting or transiently from burst-and-taper hydrocortisone therapy for Pneumocystis carinii infection.
  • Caloric deprivation, as seen in AIDS wasting, can cause irreversible deposition of acid mucopolysaccharides in the marrow space. This less vascular ground substance may predispose patients to ischemia in the interosseous space.
• Congenital dislocation of the hip: Strangulation of the afferent blood vessels occurs by forced abduction and internal rotation of the femur. The iliopsoas muscle compresses the medial circumflex vessels at the acetabular rim. Dislocation may result from abduction splinting of the hip. The incidence has been reduced by abandonment of forced reduction of the hip and the introduction of modern abduction devices. Dislocation occurs with every form of hip splintage.
• Fatty liver: Both clinical and experimental studies have shown that a fatty liver is capable of spontaneously releasing large numbers of embolic-sized fat globules into hepatic venous channels after rupture of fatty cysts into adjacent sinusoids and central veins. Hepatic perfusion in vitro studies indicate that the magnitude of fat embolism is related directly to the degree of intracellular fat present in hepatic cells at the beginning of the study.
• Femoral head fracture: The ligamentum teres usually is ruptured, disrupting a portion of the arterial supply to the femoral head. The superior retinacular vessels may be compromised (see Images 6-7).
• Femoral head dislocation: The subsynovial retinacular vessels, located along the femoral neck, may be disrupted or severely damaged. The only remaining blood supply to the femoral head may be the artery of the ligamentum teres, providing it was functional prior to the fracture.
• Sickle cell disease: Sickled erythrocytes sludge within the sinusoidal vascular bed, resulting in occlusion. Localized anoxia accentuates the sickling process, extending the area of involvement within the femoral head. AVN frequently is accompanied by osteomyelitis, especially resulting from infection by Salmonella organisms.
• Pregnancy: Impaired venous drainage by the gravid uterus places women in the third trimester of pregnancy at increased risk.

Diseases or conditions associated with or leading to AVN

• Trauma - Fracture of the femoral neck
  
  
  • Slipped capital femoral epiphysis
  • Proximal femoral epiphysiolysis
  • Dislocation of the femoral head
  • Epiphyseal compression
  • Vascular trauma
  • Burns
  • Radiation exposure
• Hemoglobinopathies
  
  
  • Sickle cell disease
  • Hemoglobin S or hemoglobin C hemoglobinopathy
  • Polycythemia
• Caisson disease - Dysbaric osteonecrosis
• Local infiltrative disease
  
  
  • Gaucher disease
  • Infection
  • Neoplasms
• Hypercortisolism
  
  
  • Corticosteroid medications
  • Cushing disease
• Alcohol consumption
• Pancreatitis
• Chronic renal failure
• Cigarette smoking
• Collagen vascular diseases
• Congenital and developmental
  
  
  • Congenital dislocation of the hip
  • Ehlers-Danlos syndrome
  • Heredity dysostosis
  • Legg-Calvé-Perthes disease
• Fabry disease
• Giant cell arteritis
• Gout and hyperuricemia
• Hemodialysis
• Hypercholesterolemia
• Hypercoagulable states
• Hyperlipidemia
• Hyperparathyroidism
• Intravascular coagulation
• Organ transplantation
• Pregnancy
• Systemic lupus erythematosus
• Thrombophlebitis
• Idiopathic

Pathology

Gross pathology

AVN of the femoral head almost always is covered by a surface of compact subchondral bone and articular cartilage. Articular cartilage derives its nourishment from synovial fluid. Only the cartilage below the tidemark may die.

Cancellous bone in the femoral head shows irregular areas of yellow necrosis extending up to several millimeters of articular cartilage. Individual trabeculae remain intact. With progression, a patchy zone of softening develops in the necrotic cancellous bone, adjacent to viable bone, representing resorption of the necrotic segment. With further weightbearing and bone resorption, structural support is lost in the subarticular region with resultant microfractures and subsequent creation of an articular sequestrum.

A line of trabecular fractures extends across the dead bone, which creates and separates an articular sequestrum. Following trabecular fracture, the load-bearing segment of the femoral head collapses. Breaks in the smooth contour of the femoral head become visible, most often at the superior margin of the fovea and beneath the acetabular lip. After collapse of the femoral head, progressive destruction of the articular cartilage and underlying bone occurs, loose bodies appear, and marginal osteophytes develop, heralding the development of DJD (see Image 8, Image 15).

Histopathology

AVN can be divided into a phase of cell necrosis followed by the repair of cancellous bone.

• Cell necrosis
  
  
  • Hematopoietic elements are the first to undergo death (within 6-12 h of the insult), followed by the death of bone cells, eg, osteocytes, osteoclasts, and osteoblasts (12-48 h) and, subsequently, by marrow fat cells (48 h to 5 d).
  • Bone infarcts can be divided into 4 zones, ie, a central zone of cell death surrounded by successive zones of ischemia, hyperemia, and normal tissue.
  • Once AVN develops, breakdown products of dead, dying, and damaged cells provide the initial inflammatory response, characterized by vasodilatation, transudation of fluid, fibrin precipitation, and local infiltration by inflammatory cells. This response forms the basis for development of the hyperemic zone and represents the initial step of repair, removal, and reconstruction of the infarcted area.
  • Complete absence of osteocytes within localized areas of trabecular bone is a reliable indicator of previous or existing AVN. This occurs approximately 2 weeks following AVN.
  • Death of marrow cells is reflected by loss of nuclei and disruption of clusters of fat cells (forming lipid cysts).
  • Mineralized bone matrix is not altered directly by AVN because death is a cellular phenomenon. The underlying supporting bony structure is unaltered initially.
• Repair
  
  
  • Bone resorption occurs first, followed by new bone formation.
  • Neither the infarcted zone nor the ischemic zone can support bone resorption or deposition. Repair begins along the outer perimeter at the junction between the dead area and the viable area containing an intact circulation (ie, hyperemic zone). This reparative response results in progressive development of a reactive margin, or interface, between the dead zone and adjacent viable tissues. Here, mesenchymal cells and capillaries proliferate and migrate along with macrophages and fibroblasts into the dead zone.
  • Resorption of dead bone and subsequent revascularization is indicated by osteoporosis.
  • Progressive loss of mechanical support due to resorption and disruption of cancellous bone within the reactive interface stimulates compensatory reinforcement of adjacent viable cancellous bone by osteoblastic activity and, less frequently, new trabeculae within the marrow space.
  • New bone formation fails to keep pace with bone resorption, resulting in significant loss of bone in the subchondral plate. Further weightbearing causes subchondral bone plate fracture and focal articular cartilage collapse (see Image 9, Image 14, Image 20, Images 25-26).
  • Fragmentation and compaction of subchondral bone debris leads to the development of a subchondral lucent area along the fracture line, which is the crescent sign seen on plain radiographs (see Image 9).
• Late complications
  
  
  • Continued weightbearing results in flattening of the articular cartilage. Capillary invasion results in articular cartilage resorption. Such a loss predisposes patients to ostearthritis (see Image 8, Image 15).
  • Extensive resorption and fibrous replacement within the reactive interface in the presence of continued weightbearing can cause fragmentation and separation of the osteonecrotic segment from the underlying viable area of the femoral head.

Frequency

United States

The incidence is approximately 15,000 cases per year. The incidence is increased because of a greater use of exogenous steroids, an increase in trauma, and alcohol abuse. Patients with diseases associated with AVN, especially patients with SLE and renal allograft transplantation recipients, are living longer and run a greater risk of developing AVN. AVN is bilateral in 30-70% of patients at the time of initial presentation. The stage of disease and time of onset is usually different in each hip. The relative frequencies of the most common causes of AVN are associated with alcoholism (20-40%) and steroid treatment (35-40%) and are idiopathic (20-40%).

• Frequency of AVN by associated conditions

• Trauma
  
  
  • Transcervical and subcapital fractures - 11-45%
  • Displaced femoral head fractures (27-30%) and undisplaced fractures (16%)
  • Reported following intramedullary nailing of a fracture of the femoral head in an adolescent
  • Up to one third of cases of AVN occurring in patients aged 4-10 years result from a fracture
  • Posterior femoral head dislocation - 10-26%
  • Anterior femoral head dislocation - Less frequent, 3-9%
  • Frequency of AVN in hips remaining dislocated longer than 12 hours that developed AVN - 52%; frequency of AVN in dislocated hips reduced within 12 hours - 22%
• Excessive alcohol intake - As many as 40% of all cases of AVN. Incidence of bilaterality as high as 73%
• Renal transplantation
  
  
  • As many as 40% of recipients develop AVN.
  • AVN is present within the first year in 40% of patients and in 85% by the second year.
  • The interval between time of transplantation and onset of symptoms is 1-126 months, with a mean of 9-19 months.
  • Within the first month following transplantation, a high association exists in patients taking prednisone doses greater than 100 mg/d.
  • In 54-80% of transplant recipients in whom AVN is detected with plain radiographs, the disease is bilateral.
• Steroid use
  
  
  • The risk is 5-25% in patients using high doses of steroids over a long term.
  • AVN is seen in 1-10% of patients treated with steroids for acute leukemia and lymphoma.
  • Of long-term survivors of bone marrow transplantation, AVN occurs in 10% of patients who received high doses of steroids for the prevention or treatment of graft-versus-host disease.
  • Of patients receiving steroid replacement therapy, 2% develop AVN.
• Systemic lupus erythematosus - 5-40%. As many as one third of patients are receiving high-dose steroids.
• Sickle cell disease - In SS disease, 4-12% and in SC disease, 20-68% (see Pathophysiology for explanation of SS vs SC disease)
• Hemophilia - Approximately 3%
• Rheumatoid arthritis - Approximately 12% (most cases associated with steroid treatment)
• Slipped capital femoral epiphysis - Approximately 15% and less than 7% in hips reduced within 24 hours and 17% after 24 hours
• Legg-Calvé-Perthes disease - Bilateral in 15-20%

International

SCD and the hemoglobinopathies are the major cause of AVN in African countries such as the Democratic Republic of the Congo (formerly Zaire). Thalassemia is prevalent in southern Mediterranean Europeans and people from Southeast Asia. LCP disease has a greater incidence in Japanese, Mongolian, and Central European children. The incidence is low in blacks and American Indians.

Mortality/Morbidity

Severe joint destruction resulting from deterioration and leading to a major surgical procedure occurs within 3 years following diagnosis in 50% of patients. Femoral head collapse usually occurs within 2 years after development of hip pain.

Race

Predisposing conditions, such as SCD, are concentrated in the African American population. Beta thalassemia is common in Southern Europeans and Southeast Asians.

Sex

LCP disease affects males 4 times more frequently than it affects females.

Age

AVN usually occurs in patients in the third-to-fifth decades unless predisposing conditions exist that place different age groups at risk, ie, LCP and slipped capital femoral epiphysis.

Anatomy

Gross anatomy

The hip is a ball-and-socket joint. The acetabulum, which provides bony coverage of 40% of the femoral head, has a horseshoe-shaped lunate surface. The femoral head is round and smooth in all imaging planes. The fovea capitis, a small depression on the medial femoral head, is the site of attachment of the ligamentum teres (see Image 3).

The principal sources of blood flow to the femoral head are the LEVs, branches of the posterior superior retinacular vessels (PSVs), which are branches of the medial femoral circumflex artery, a branch of the profunda femoris artery (see Images 6-7). The PSVs run along the posterior-superior aspect of the femoral neck under the synovial membrane. They are extraosseous in location and give rise to the LEV (see Images 6-7).

The LEV enters the femoral head within a 1-cm wide zone between the cartilage of the femoral head and the cortical bone of the femoral neck. They supply the lateral and central thirds of the femoral head (see Images 6-7). When patent, the ALT supplies the medial third of the femoral head.

Branches of the LEVs and ALT anastomose in the junction of the central and medial third of the femoral head. The thickest part of the articular cartilage of the femoral head is located along the posterior-superior aspect and measures 3 mm in diameter. It thins to 0.5 mm along the peripheral and inferior margins.

Blood supply in children

Vascular anatomy of the proximal femur is in a transitional stage of development in children aged 4-7 years. The ALT does not penetrate the epiphysis of the femoral head until age 9 or 10 years. The medial circumflex artery, a branch of the profunda femoris artery, penetrates into the femoral proximal metaphysis but is prevented from passing into the femoral epiphysis by the growth plate. Thus, the blood supply to the femoral head is especially vulnerable during this time.

CT anatomy

Physiologic thickening of bone trabeculae in the center of the femoral head is present and appears similar to a star, which is termed the asterisk sign. The configuration is related to the stress of weightbearing (see Image 1).

Sclerotic raylike branches of the star usually extend to the upper surface of the femoral head (see Image 1). A dense line, extending from the lateral to the medial portion of the mid femoral head, represents the fused epiphysis.

MRI anatomy

Fatty marrow is present in the femoral capital epiphysis and the greater trochanter of all individuals older than 2 years. Fatty marrow has high signal on T1-weighted images (T1WIs) and T2-weighted images (T2WIs; see Images 3-5). Hematopoietic marrow, when present, is found in the femoral neck, intertrochanteric region, and acetabulum. It has low signal on T1WIs and high signal on T2WIs (see Images 4-5).

The medullary cavity contains prominent vertically orientated linear striations of low signal on all imaging sequences extending from the inferolateral aspect to the superomedial aspect of the femoral head. These represent the weightbearing trabeculae and are analogous to the asterisk sign seen on CT scans (see Images 3-5). The medullary cavity is surrounded by a sharply marginated low-intensity line representing the cortex of the bone. Cortex and trabeculae have weak MRI signals because of a low concentration and decreased mobility of hydrogen ions (see Images 3-5).

A thin high-signal line, representing the articular cartilage, surrounds the outer margin of the femoral head. A curvilinear low-signal line, representing the physis, crosses the marrow of the femoral neck laterally to medially (see Images 3-5). The medullary cavity of the iliac bone, adjacent to the acetabulum, contains signal that is slightly lower and less homogeneous in signal than that of the femoral head (see Images 4-5).

Clinical Details

AVN demonstrates no distinguishing clinical features. Patients do not experience pain during the ischemic episode. Occult AVN can be present for more than 5 years before the onset of symptoms. Patients may be asymptomatic or may develop pain gradually and insidiously, experience a decreased range of motion (ROM), and walk with a limp. Pain can be excruciating and of sudden onset, with the patient able to note the exact time and date it began.

Radiographic findings may appear after a delay of several months to years following the onset of symptoms.

Pain

• Pain can be focal, over the groin or hip, or it can radiate to the buttocks, anteromedial thigh, or knee.

• Pain can be induced mechanically by standing and walking and can be eased by rest.

• Pain can be very intense, especially in the large infarcts often seen in Gaucher disease, dysbarism, and hemoglobinopathies.

• Pain has been described as throbbing, deep and, often, intermittent.

• Pain can be worsened by coughing and may worsen at night.

• When the disease is chronic, pain can be vague.

• In AVN, 40% of patients have night pain that may be associated with morning stiffness.

• Patients with pain of several months duration may notice a sudden increase in pain.

• Following treatment of a traumatic hip fracture, AVN may manifest as worsening pain.

• In elderly patients, pain may be of sudden onset with no history of trauma.

• Early in the course of the disease, there is frequently a clear dissociation of pain, which can be considerable, and limitation of movement, which can be minimal.

Click

• A click may be heard when the patient rises from a sitting position.

• A click may be elicited by external rotation of an abducted hip.

Range of motion

• ROM may be diminished, especially after collapse of the femoral head.

• ROM may be limited, especially in flexion, abduction, and internal rotation.

• Gait: Patients may walk with a limp. The Trendelenburg sign may be positive.

Clinical summary

For AVN to be diagnosed at an early stage, the physician must have a high index of suspicion, especially regarding patients who have any of the risk factors and negative radiograph findings. This is especially true with unilateral involvement because of the high risk of developing AVN in the contralateral hip. These patients should be evaluated aggressively.

Preferred Examination

MRI

MRI is the most sensitive means of diagnosing AVN. MRI provides the criterion standard of noninvasive diagnostic evaluation. It is more sensitive than CT scanning or planar scintigraphy, and is much more sensitive than plain film radiography for detecting AVN.

Low-field magnets (0.1 T) are not as sensitive for diagnosing AVN. Similar sensitivity and specificity were found between low-field MRI and planar radionuclide bone scanning. At high magnetic field strength, MRI has a higher sensitivity than radionuclide scanning. Using a 1.5-T magnet, Beltran et al found 88% sensitivity, 100% specificity, and 94% accuracy for MRI and 78% sensitivity, 75% specificity, and 76% accuracy for bone scintigraphy. The high sensitivity of MRI has been confirmed by others.

MRI performed at 0.6 T and single-photon emission computed tomography (SPECT) bone imaging using technetium Tc 99m methylene diphosphonate were similarly effective in diagnosing AVN. MRI had a sensitivity of 87% and a specificity of 83%. SPECT had a sensitivity of 91% and a specificity of 78%. Both were more effective than planar bone scintigraphy, which had a sensitivity of 83% and a specificity of 83%.

In nonpainful hips, MRI was more effective than SPECT for diagnosing AVN. MRI detected AVN in 10 of 15 patients, but SPECT detected AVN in only 5 of 15 patients SPECT.

Using receiver operating characteristic (ROC) curves, MRI was better than CT by more than 2 standard errors and better than radionuclide scanning by more that 3 standard errors in helping diagnose early AVN. MRI has a high sensitivity for diagnosis of bone marrow abnormalities. The sensitivity of MRI in diagnosis of AVN is 85-100%. MRI has 97% sensitivity in helping differentiate AVN from the normal hip.

In differentiating AVN from non-AVN disease of the femoral head, MRI demonstrates a sensitivity of 98% and a specificity of 85%. Before femoral head collapse, specificity is 75-100%. After femoral head collapse, sensitivity is 100%.

MRI is indispensable for the accurate staging of AVN because images clearly depict the size of the lesion, and gross estimates of the stage of disease can be made. MRI allows sequential evaluation of asymptomatic lesions that are undetectable on plain radiographs. MRI facilitates better response to treatment since AVN is diagnosed at an earlier stage and therapeutic measures are more successful the earlier the stage of initiation.

MRI lacks ionizing radiation, which is especially important in the growing skeleton. It is accepted widely and is easy to perform. MRI is capable of imaging in multiple planes (ie, axial, sagittal, coronal, or any variation thereof). MRI demonstrates superior soft tissue resolution and has high spatial and contrast resolution, allowing evaluation of morphologic features.

MRI can help guide interventional procedures such as core decompression. It can demonstrate response of the femoral head to treatment. MRI images can detect the joint effusions and bone edema that often accompany the disease. MRI is a noninvasive means for evaluating articular cartilage congruity and allows sequential evaluation of asymptomatic lesions undetectable on plain radiographs.

Single-photon emission computed tomography

Initially, SPECT images reflect vascular integrity. Early in the disease, scans may demonstrate an avascular focus in the presence of normal MRI findings unless MRI contrast is used. Collier found a sensitivity of 85% for SPECT. With triple-head high-resolution SPECT, Lee et al found sensitivity to be 97%.

SPECT provides images of the radioactivity within the target organ in 3 dimensions. It can separate overlying and underlying radioactivity into sequential tomographic planes, increasing image contrast and improving lesion detection and localization compared to planar scintigraphy. SPECT eliminates radioactivity resulting from hyperemia about the hip joint and from the underlying acetabulum and adjacent bladder. SPECT is used as an alternative when MRI cannot be performed or when MRI results are indeterminate.

Planar radionuclide imaging

Collier found sensitivity of 55% with planar radionuclide imaging. Bone scintigraphy equipped with a pinhole collimator has a greater sensitivity for diagnosing AVN than bone scintigraphy using a high-resolution parallel-hole collimator.

Bone scintigraphy using pinhole collimation

The pinhole collimator is a conical collimator with a small circular aperture (3-5 mm) that produces an inverted image of the object in a manner analogous to photographic cameras. The image obtained is magnified, allowing better visualization of small structures and improving detection of scintigraphic abnormalities. The pinhole collimator optimizes resolution in evaluating circumscribed areas. Acquisition time is only 15 minutes compared to up to 45 minutes for SPECT. The technique provides an alternative when MRI cannot be performed or when MRI results are not clearcut.

Planar scintigraphic imaging using quantitative bone scan

This technique provides physiologic data not obtained with other modalities, including MRI, such as quantification of uptake in the perfusion and static phases. It requires correct computer programming only.

CT

The high spatial and contrast resolution of CT allows analysis of morphologic features (see Images 1-2, Images 13-15). Sensitivity in detecting early AVN is 55%, which is similar to planar nuclear medicine imaging. CT is more appropriate in evaluating the extent of involvement, such as subchondral lucencies and sclerosis present in the reparative stage before the onset of femoral head collapse and superimposed degenerative disease.

CT is better able to help define the extent of disease at stages II and higher than MRI and plain film. CT enables detection of subchondral or cancellous fractures and collapse, especially when using multiplanar reconstruction. This information is essential for planning treatment (see Images 13-14).

Plain film radiography

Although unable to indicate stage 0 and 1 disease, plain film can help assess flattening of the femoral head and associated degenerative disease (see Images 8-9, Images 20-21, Images 25-26).

Limitations of Techniques

MRI

Rarely, bone biopsy analysis was reported to be positive when MRI findings were normal. MRI cannot be performed in patients with cardiac pacemakers, intracranial clips, or claustrophobia. Problems related to malpositioning can lead to misrepresentation. In children, slight pelvic obliquity may cause the normal dark-appearing growth plate to appear in the same axial cut as the contralateral bright-appearing epiphysis and may be interpreted as abnormal.

Children may require sedation due to long imaging times. Detection after surgery to repair a hip fracture may be difficult because of the presence of orthopedic hardware, which creates significant image distortion. Marrow cells are more resistant to ischemia than hematopoietic cells or osteocytes. Since MRI images reflect changes within marrow fat signal intensity, MRI findings of AVN may not be seen for up to 5 days after the ischemic event, until the marrow fat cells have died. In this situation, contrast-enhanced MRI is needed.

Single-photon emission computed tomography

SPECT demonstrates poor spatial resolution. Artifacts from the bladder frequently are encountered, which may obscure the photon-deficient region of the femoral head. A number of techniques, such as the use of multihead cameras with shorter acquisition times that improve resolution and increase sensitivity, have been advocated, but none has gained universal acceptance.

SPECT imaging requires a cooperative patient who must remain immobile for up to 45 minutes of acquisition time. Diagnosing LCP in small children may be difficult because of the small size of the femoral epiphysis and associated bladder artifacts. SPECT is difficult to use in children because of the necessity to remain motionless for long periods of time. Children may require sedation.

Planar scintigraphy

This technique demonstrates poor spatial resolution (see Image 16, Image 24). The ring of increased activity reflecting hyperemia in the early stages and bone healing later obscures the photon-deficient necrotic center within the femoral head, which is indicative of AVN. The site may show a uniform high level of activity making it impossible to distinguish AVN from other causes of increased activity, such as osteoarthritis, fracture, and inflammatory arthritis. A cold spot in the femoral head is highly specific but not sensitive for diagnosing AVN.

Artifacts from radioactivity in the bladder frequently are encountered, obscuring the photon-deficient region. Entities causing increased uptake about the hip joint, such as arthritis and inflammatory disease, may obscure the photopenic necrotic focus within the femoral head. Results can be judged only by comparison with the other hip and may be of little use in the presence of bilateral involvement.

Planar scintigraphy using quantitative bone scan

This technique is experimental and is not used widely in the clinical setting.

CT

Although CT may delineate subtle alterations of bone density when plain radiograph findings are normal, MRI and SPECT scintigraphy are much more sensitive for evaluating early manifestations of the disease, ie, bone marrow edema. CT scans are insensitive for detecting stage 0 and 1 AVN but are excellent for detecting femoral head collapse, early DJD, and the presence of loose bodies.

CT may improve the accuracy of radiographic staging using thin-slice thicknesses of 1 mm or less and by incorporating multiplanar reconstruction. In one study, 30% of hips with stage 2 (precollapse) AVN, evaluated with plain film radiography, had stage 3 disease when evaluated using CT scans.

Plain film radiography

Using plain film, the sensitivity for detecting early stages of the disease is as low as 41%. Plain film does not detect stage 0 and 1 AVN. A delay of 1-5 years can occur between the onset of symptoms and the appearance of radiographic abnormalities. Normal radiographic findings do not necessarily indicate a normal hip.

Demineralization of the femur may be detected and the disease suggested only after bone resorption has occurred. If early diagnosis is needed for the prompt initiation of therapy, more sensitive imaging methods (ie, MRI) must be used, especially in populations at increased risk for developing AVN.

DIFFERENTIALS

Section 3 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Intervention
• Multimedia
• References

Other Problems to be Considered

Clinical

Transient osteoporosis

Plain film radiography

Malignancy
Osteomyelitis
Transient osteoporosis of the hip
Bone sarcoma
Advanced DJD (see Image 9)
Insufficiency fractures
Epiphyseal dysplasia
Bone metastases

Bone scintigraphy

Infection
Plasma cell myeloma
Skeletal metastasis
Hemangioma
Radiation therapy
Arthritis
Sympathetic dystrophy
Bone marrow edema syndrome
Bone metastases

CT

Degenerative disease
Insufficiency fracture
Malignancy
Infection
Plasma cell myeloma
Bone metastases

MRI

Transient osteoporosis of the hip
Transient bone marrow syndrome
Bone bruise
Epiphyseal stress fracture
Infection
Infiltrative neoplasm
Insufficiency fracture
Bone metastases

RADIOGRAPH

Section 4 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

A staging system using radiographic findings has been developed by Ficat and Arlet and has been used widely for treating AVN. This has been supplanted by the classification system of Steinberg et al (see below), which incorporates MRI and scintigraphic findings.

Stage 0 (preclinical and preradiologic)

AVN can be suggested only if it has already been diagnosed in the contralateral hip.

Stage 1 (preradiologic)

Since the advent of MRI, stage 1 is defined by normal findings on radiographs and positive findings on MRI or bone scintigraphy. Stage 1 represents the early resorptive stage. Late in this stage, plain radiographs may show minimal osteoporosis and/or blurring and poor definition of the bony trabeculae. Osteoporosis appears when one third of the mineral content of bone has been lost.

Stage 2 (reparative)

Stage 2 represents the reparative stage before flattening of the femoral head occurs. Stage 2 can extend for several months or longer. Demineralization now is evident. It may be generalized or patchy or appear in the form of small cysts within the femoral head. Demineralization is the first manifestation of the reparative stage and it represents resorption of dead bone.

Patchy sclerosis appears after demineralization develops, usually in the superolateral aspect of the femoral head (see Image 17, Image 21). Patchy sclerosis appears as increased density on radiographs and may be diffuse, focal, or in a linear arc, which is concave superiorly. It represents apposition of new bone on dead trabeculae. The pattern demonstrates alternating areas of lucency and sclerosis. Patchy sclerosis usually coexists with demineralization, appearing as alternating regions of increased density and increased lucency.

Stage 3 (early collapse of the femoral head)

A linear subcortical lucency, representing a fracture line, is present immediately beneath the articular cortex. It may extend into the articular cartilage at the superolateral aspect of the femoral head. This is termed the crescent sign and is best demonstrated on a frogleg view (see Image 9 and Image 32). The subarticular cortex may remain attached to the cartilage and is separated from the underlying femur by soft tissue, termed the eggshell sign. The femoral head initially preserves its round appearance, but later, it demonstrates collapse. This may be indicated by joint-space widening.

Stage 4 (progressive degenerative disease)

Further flattening of the femoral head occurs with loss of its smooth convex contour (see Image 26). Ultimately, the superior femoral fragment, representing the articular surface and the immediate subchondral bone, may become separated from the underling femoral head or depressed and compacted into the femoral head. Fragments of bone and cartilage may separate from the underlying femur, roam freely within the hip joint, and become loose bodies.

Severe collapse and destruction of the femoral head leads to progressive DJD with joint space narrowing, marginal osteophyte formation, and subchondral cyst formation. Subchondral cysts usually can be differentiated from the alternating sclerosis and the lucency of the reparative stage of AVN.

Atypical radiographic findings

• Atypical findings consist of early joint space narrowing, often before the appearance of the crescent sign. Unless the physician holds a high index of suspicion, an incorrect diagnosis of ostearthritis will be made.
• Atypical findings are seen in 18% of patients.
• Atypical findings are seen in patients on steroid therapy.
• Signs of bone repair (sclerosis) may be absent. Here, the first radiologic manifestations may be the subchondral lucency representing fracture of the dead bone.
• Atypical findings occur because bone formation is decreased in the presence of normal bone resorption. In this situation, increased density within the femoral heads usually is a result of flattening from fracture and compression of the femoral head.

Steinberg et al proposed a 6-stage classification system based on that of Ficat and Arlet (see below for radiographic findings).

• Stage 0 is both preclinical and preradiologic. Most patients with stage 0 disease are identified when imaging is performed to evaluate AVN in the contralateral hip or to exclude other diseases.
• Stage 1 demonstrates normal radiograph findings or shows minimal demineralization or blurred trabeculae. Pain in the anterior groin or thigh is common. Limited ROM in the hip may be present.
• Stage 2 shows diffuse or localized areas of sclerosis, lucencies, or both within the femoral head. Clinical signs persist or worsen.
• Stage 3 is characterized by the crescent sign (subchondral fracture).
• Stage 4 demonstrates marked collapse and fracture involving the articular surface. Segmental flattening of the femoral head demonstrates an out-of-round appearance.
• Stage 5 is characterized by the development of DJD.

Steinberg radiologic clinical classification findings for the staging of AVN of the femoral head

• Stage 0 - Abnormal MRI findings, normal radiograph findings, and normal bone scan findings
• Stage 1 - Abnormal bone scan findings, mild groin pain, and normal radiographs findings
• Stage 2 - Osteoporosis, groin pain, and mottled sclerotic and/or cystic areas
• Stage 3 - Crescent line, pain with subchondral fracture activity, and no femoral head flattening
• Stage 4 - Segmental flattening, pain with femoral head activity, no acetabular involvement, and normal joint space
• Stage 5 - Joint space narrowing, resting pain, and acetabular degeneration (DJD)

Advanced staging of AVN using plain radiography

• The Osseous Circulation Research Association of the Toulouse, France-based Association Internationale de Recherche sur la Circulation Osseuse has proposed a further classification of the various stages of AVN, which incorporates the percentage (area) of involvement of the femoral head and the location of the lesion.
• The extent of the AVN lesion is an important determinant of both clinical and radiologic outcomes.
• Three types of involvement have been identified.
  
  
  • Mild: Less than 15% of femoral head involvement is noted, which is less likely to demonstrate radiographic progression or require hip prosthesis.
  • Moderate: Involvement is from 15-30%.
  • Severe: Involvement is greater than 30%.

Moderate and severe involvement are more likely to progress radiographically to degenerative disease and to require hip prosthesis placement.

Degree of Confidence

Demineralization: A nonspecific finding seen in a large number of different diseases. Such a finding needs further evaluation using MRI to evaluate for AVN.

Alternating areas of lucency and sclerosis: This is characteristic for stage 2 disease. Rarely, this finding is confused with entities such as chondroblastoma. This radiolucent cartilaginous tumor contains calcium and is located in the epiphyseal region. If questions are present concerning the presence of the disease, MRI is recommended. If not, treatment can be initiated.

Degenerative joint disease: DJD with degenerative spurring and joint space narrowing with subchondral cyst formation may mimic AVN. Subchondral cysts usually are immediately adjacent to areas of joint space narrowing and osteophyte formation. MRI is usually diagnostic in problematic cases. Rarely, biopsy may be needed for differentiation.

False Positives/Negatives

False-positive findings

Poorly defined radiolucent lesions may simulate the bone destruction seen in malignancy, osteomyelitis, and transient osteoporosis of the hip (TOP). For malignancy and osteomyelitis, the history may be helpful.

Demineralization can be seen in a number of different diseases including TOP. TOP is self-limiting and resolves within 4-10 months. Radiologic resolution lags behind clinical improvement by 4-8 weeks, at which time, radiograph findings revert to normal. The healing and reparative phase may mimic bone sarcoma.

The later stages of AVN, which are characterized by joint space narrowing, articular cartilage destruction, and alternating areas of lucency and sclerosis within the femoral head, may mimic DJD with subchondral cyst formation (see Images 8-9, Image 28).

Sclerosis adjacent to an insufficiency fracture is an important differential, especially in patients who are osteopenic and are taking steroids.

CT SCAN

Section 5 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

CT scans do not demonstrate the early vascular and marrow abnormalities that result in osteonecrosis.

Early CT signs of AVN

• Osteoporosis is the first sign visible.
• Later, the central bony asterisk is distorted, appearing as clumping and fusion of the peripheral asterisk rays. Clumping appears as spots or as hyperdense "roads" of various width (see Image 13). This represents changes in the sclerotic interface between necrotic and viable bone and is analogous to the line of low signal surrounding the necrotic bone seen on MRI images.
• Early signs are caused by microfractures resulting from reduced mechanical load of dead bone trabeculae, altering the shape of the asterisk.
• Signs also are related to new bone formation on the dead trabeculae.
• The lucent cystic region, representing the reparative zone, may be appreciated (see Image 13).

Degree of Confidence

Osteoporosis, whether diagnosed using plain film radiography or CT, must be evaluated further because it is present in a great number of diseases. MRI findings usually are diagnostic.

False Positives/Negatives

Unless the asterisk sign is appreciated, articular surface abnormalities may be interpreted as DJD. The lucency within the reparative zone may be confused with malignancy, infection, insufficiency fracture, or plasma cell myeloma.

MRI

Section 6 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

Technical considerations

• The coronal plane is the most important imaging plane for evaluating AVN.
• Sagittal images may help eliminate partial-volume averaging, which is especially present on axial images.
• Off-coronal images, angled toward the axial plane, may demonstrate AVN better when the lesion is located anterosuperiorly.
• Since both hips often are involved and AVN is silent early in the course of the disease, use of a body coil and a large field of view (30-40 cm) is necessary to image both hips simultaneously.
• Surface coils, including shoulder coils, flexible coils, and phased-array coils, may provide additional resolution for individual hip joints in selected patients.
• T1WIs and T2WIs are obtained in the coronal plane, 4-mm thick, with a 1-mm gap.
• Fast spin-echo (FSE) images with fat saturation also may be obtained.
• Short tau inversion recovery (STIR) images provide excellent fat suppression and demonstrate areas of bone marrow edema (see Images 10-11). STIR images may be obtained using FSE techniques with an echo train length of 8-16. This helps reduce lengthy imaging times associated with STIR imaging.
• A frequency selective pulse may be added to suppress the fat signal. When applied, the inner bright line on T2WIs is visualized, but the dark outer peripheral band is not seen. Nevertheless, FSE T2WIs with fat suppression are useful in demonstrating the extent of marrow edema associated with AVN.
• Rapidly acquired MRI sequences can reveal the presence of AVN reliably. These rapid screening sequences reduce or eliminate artifacts caused by patient motion. Coronal 2-dimensional fast low-angle shot (2D FLASH) T1WIs are performed using repetition time (TR) 174.9, echo time (TE) 4.1, flip angle 70°, 4-mm slice thickness with 20% interslice gap, matrix 172 x 256, number of signal acquisitions 1, and imaging time 39 seconds. Axial fat-suppressed FSE T2WIs are performed using TR 3500, TE 138, echo train length 29, 6-mm slice thickness with 25% interslice gap, matrix 116 x 256, number of signal acquisitions 1, and imaging time 16 seconds.
• Chemical shift imaging may be used to detect premature fatty marrow conversion associated with AVN. Fatty and hematopoietic marrow and the distribution of water within the ischemic focus can be differentiated on fat-selective and water-selective images.
• Gradient-echo images are not as sensitive for fluid within reparative tissue but they can demonstrate joint effusions, subchondral fluid, and changes in the contour of the articular cartilage.

Screening for AVN using T1WI only

• Reduces specificity
• May fail to identify a transchondral fracture
• May not help diagnose other diseases in which clinical presentation may mimic AVN, including transient osteoporosis

Khanna, et al described a limited magnetic resonance examination using coronal T1-weighted images. Only one case of AVN was missed in 29 patients. The time required for the exam was 10 minutes as opposed to 30 minutes, required for the full exam. Relative costs of the screening and full exams, without calculating the professional component were $104 and $312 respectively. Other diseases, causing hip pain, such as myositis, greater trochanteric bursitis, labral cysts and fractures, located distant from the femoral heads were missed when T2 weighted images were not obtained. Perhaps there may a role for the limited exam in following up bone marrow edema in asymptomatic patients.

MRI findings

• T1-weighted images: A peripheral band of low signal is present in the superior portion of the femoral head outlining a central area of bone marrow. This is considered to represent the reactive interface between the necrotic and reparative zones and extends to the subchondral bone plate (see Image 18, Image 22, and Image 30).
• T2-weighted images: The inner border of the peripheral band demonstrates high signal. This may represent chemical shift artifact because the position of the signal changes when the phase and frequency directions are changed. This is termed the double-line sign and is pathognomonic for AVN (see Image 27). It is present in 80% of cases. This is not demonstrated well on FSE T2WIs because of the increased signal intensity of fat, present on this sequence, which obscures the bright inner line (see Image 31). To compensate, a frequency selective pulse is added to suppress the signal from fat. If fat suppression is used, the dark outer peripheral band of AVN is not demonstrated well, in contrast to the inner high-signal band visualized on this sequence.
• The outer low-signal ring represents the interface of repair tissue with the necrotic zone.

Classification of the AVN lesion into 4 types according to alterations in central avascular segment signal

• Class A: Central osteonecrotic focus signal analogous to that of fat. Increased signal is demonstrated on T1WIs, and intermediate-to-high signal is demonstrated on T2WIs (see Image 19).
• Class B: Central osteonecrotic focus signal analogous to that of blood. Increased signal is demonstrated on both T1WIs and T2WIs (see Images 22-23).
• Class C: Central osteonecrotic focus signal analogous to that of fluid. Decreased signal is demonstrated on T1WIs and increased signal is demonstrated on T2WIs (see Images 10-12, Images 18-19, and Images 22-23).
• Class D: Central osteonecrotic focus signal analogous to that of fibrous tissue. Decreased signal is demonstrated on both T1WIs and T2WIs.

Use of contrast enhancement

If intravenous contrast is used to supplement the MRI examination, areas of decreased enhancement indicate early AVN despite normal findings on pre-enhancement images. Contrast enhancement is useful for distinguishing viable from nonviable trabeculae and marrow. Nonviable tissue does not enhance after contrast administration. Enhancement of the low-signal band on T1WIs corresponds to the reparative zone.

Atypical MRI findings

AVN occasionally appears as an area of abnormal signal involving the femoral head, neck, and intertrochanteric region. It is characterized by decreased signal on T1WIs and increased signal on T2WIs without the focal lesions that are pathognomonic for AVN. This is termed the bone marrow edema pattern, since the signal characteristics are consistent with increased free water or edema within the normal fatty marrow of the proximal femur. This may reflect early edema before the onset of focal abnormalities and may indicate the period of time between cell death and development of a significantly large reactive interface, which is recognizable as AVN on MRI scans.

Differentiation of transient from irreversible AVN lesions using subchondral marrow changes on T2WIs or contrast-enhanced T1WIs

Absence of low-signal subchondral lesions and subchondral deformities in the presence of the bone marrow edema pattern represents transient osteoporosis. Areas of low signal intensity in the subchondral region and contour deformities of the femoral head are typical of AVN.

Associated findings

Fatty conversion of marrow is a prerequisite for developing AVN of the femoral head. This finding may help identify populations at increased risk for developing AVN. Subchondral fractures may appear as a low signal intensity gap on T1WIs. They can appear as regions of high signal intensity, representing fluid within the fracture line, on T2WIs. Joint effusions are present in 50% of patients (see Images 10-11).

Correlation of MRI staging with radiographic staging

• Classes A and D showed the best correlation with radiographic staging.
• Approximately 50% of radiographic stage 1 and 83% of radiographic stage 2 lesions demonstrated MRI class A signal pattern.
• In those femoral heads complicated by fracture (radiographic stages 3 and 4), only 14% were class A and 43% were class B.
• Class B and C MRI lesions correlate poorly with radiographic staging.

Correlation of clinical symptoms with MRI class

• Of patients with MRI class A lesions, 54% were asymptomatic.
• Of patients with MRI classes B and C lesions, 11% were asymptomatic.
• Of patients with MRI class D lesions, 67% were asymptomatic.

Correlation of MRI findings to prognosis

MRI classes, unlike radiographic stages, have little predictive value regarding prognosis for femoral head collapse. Entirely circumscribed AVN that did not extend to the subchondral margin had a good outcome, independent of the overall size of the lesion. The percentage of the weightbearing surface occupied by the lesion was the most reliable factor in predicting outcome.

Basing outcome on overall extent of involvement of the femoral head is controversial. Lafforgue et al evaluated three different means of determining femoral head involvement and found that the percentage of weight-bearing femoral cortex involved with AVN was the most reliable parameter in determining outcomes. Beltran et al found that femoral head collapse occurs in most patients with a large area of AVN before the appearance of a subchondral fracture, even if core decompression is performed. Using MR imaging they determined femoral head collapse did not occur when less than 25% of the weight-bearing surface was involved.

Tendency toward femoral head collapse in relation to lesion size as demonstrated on MRI

Tendency as determined using MRI findings is in agreement with the quantitative radiographic staging of Steinberg et al. Small lesions confined to the medial anterosuperior portion of the femoral head tended not to collapse over a 28-month follow-up period. More extensive lesions collapsed, with a 50% collapse rate within 12 months. Shimizu et al found a 74% rate of femoral head collapse by 32 months if the region of AVN involved more than two-thirds of the weight bearing surface area.

Degree of Confidence

Bone marrow edema: This is a nonspecific finding seen in this and other conditions. It may progress to frank AVN (see Images 29-31).

TOP: This is a self-limiting condition characterized by osteoporosis of the femoral head and, occasionally, the femoral neck. TOP resolves over a 4- to 10-month period, and it does not progress to AVN. TOP often can appear on both sides of the hip joint, differentiating it from AVN. Similar findings can develop in the contralateral hip or other joints, in which case, it is termed regional migratory osteoporosis. TOP occurs in patients without the risk factors for AVN.

Transient bone marrow syndrome: This is similar to TOP, but osteoporosis is never present radiographically. Symptoms are self-limiting and it occurs in patients who have no risk factors for AVN.

Bone bruise: This condition usually is self-limiting and resolves over time. If bone marrow edema is present on MRI, plain radiographs are obtained. If plain film findings are normal, radiographs should be repeated within 4-6 weeks. If osteoporosis is detected, it is believed to represent TOP. If osteoporosis is absent, patients may be placed into groups with and without high risk factors for developing AVN. Patients with factors indicating a low index of suspicion can be treated conservatively but plain radiograph and MRI follow-up imaging should be performed. High-risk patients should be considered candidates for surgical intervention.

Subchondral fracture: An area of increased signal on T2WIs in the subchondral zone may represent fracture or edema. To accurately stage the disease, CT scans are helpful in differentiating the two conditions.

False Positives/Negatives

False-negative MRI diagnosis may be related to the use of T1WIs only. These images are less sensitive to detecting the bone marrow edema pattern of early AVN. This is detected better using T2WIs or STIR images.

NUCLEAR MEDICINE

Section 7 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

Single-photon emission computed tomography

A cold spot (photon-deficient region) within the femoral head is highly specific for AVN and is the earliest scintigraphic evidence of AVN. This usually is seen 7-10 days after the ischemic event.

Over a period of weeks to months, increased uptake representing revascularization and repair surrounds and eventually replaces the region of photopenia. The central region of photopenia with surrounding zone of increased uptake is termed the doughnut sign.

Perfusion and static planar radionuclide imaging

Initially, uptake is decreased in the perfusion and static phases, which represents the early ischemic event. Later, uptake is decreased within the femoral head in the perfusion phase and increased around the cold region in the static phase. The latter represents the reactive zone around the infarcted segment. The increased uptake from the reparative zone eventually replaces the photopenic region.

Degree of Confidence

A cold spot can be seen in other conditions, such as infection, metastasis, joint effusion, and plasma cell myeloma. Spencer et al reported that not all adults take up radiopharmaceutical in the femoral head. As a result, MRI is needed for confirmation.

False Positives/Negatives

False-negative findings in planar scintigraphy

Hungerford reported false-negative bone scans in the hips of 14 of 27 patients, 13 of whom had bilateral disease. In patients with bilateral involvement, the uptake, although symmetric, really is increased bilaterally. If the uptake is asymmetric, the side affected more severely makes the less-involved side appear falsely normal.

Later in the course of the disease, between the time of infarct and revascularization, the scan appears falsely normal in 6-10% of patients or it demonstrates a pattern of uptake that cannot be differentiated from DJD.

False-positive findings in planar scintigraphy

Decreased uptake, indicative of early AVN, also can be seen in infection, plasma cell myeloma, skeletal metastasis, hemangioma, and radiation therapy.

Increased uptake alone can be seen in arthritis, sympathetic dystrophy, malignancy, infection, TOP, hemangioma, and insufficiency fractures. TOP can cause increased uptake on both sides of the hip joint.

INTERVENTION

Section 8 of 10  

• Authors and Editors
• Introduction
• Differentials