AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

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INTRODUCTION

Section 2 of 11  

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Background

Avascular necrosis (AVN) is defined as cellular death of bone components due to interruption of the blood supply; the bone structures then collapse, resulting in bone destruction, pain, and loss of joint function. AVN is associated with numerous conditions and usually involves the epiphysis of long bones, such as the femoral and humeral heads and the femoral condyles, but small bones can also be affected. AVN of the jaw associated with bisphosphonate use was recently described. In clinical practice, AVN is most commonly encountered in the hip.

Early diagnosis and appropriate intervention can delay the need for joint replacement. However, most patients present late in the disease course. Without treatment, the process is almost always progressive, leading to joint destruction within 5 years. Patients taking corticosteroids and organ transplant recipients are particularly at risk of developing AVN. Most available data regarding the natural history, pathology, pathogenesis, and treatment of AVN pertains to femoral head necrosis.

Pathophysiology

Although the pathophysiology of AVN is not fully understood, the final common pathway is the interruption of blood flow to the bone. AVN affects bones with a single terminal blood supply such as the femoral head, carpals, talus, and humerus. These bones have limited collateral circulation. Interruption of the vascular supply and resultant necrosis of marrow, medullary bone, and cortex are theorized to be caused by the mechanisms listed below. However, individual patients usually have more than one risk factor; this indicates that the pathogenesis is likely multifactorial.

• Vascular occlusion: This is characterized by the interruption of the extraosseous blood supply via factors such as direct trauma (eg, fracture, dislocation), nontraumatic stress, and stress fracture.
• Altered lipid metabolism: Animal studies have led to the hypothesis that increased levels of serum lipids leads to lipid deposition in the femoral head, causing femoral hypertension and ischemia. Lipid-level–lowering drugs in animals reverse this process. Corticosteroids administration was associated with fat emboli in the femoral heads of rabbits.
• Intravascular coagulation: Disorders of the coagulation system have been implicated in the pathogenesis of AVN. Typically, it is a secondary event triggered by a familial thrombophilia, hypercholesterolemia, allograft organ rejection, or other disorders such as infection, malignancy, or pregnancy.
• Healing process: Necrotic bone triggers a process of repair that includes osteoclasts, osteoblasts, histiocytes, and vascular elements. Osteoblasts build new bone on top of the dead bone, leading to a thick scar that prevents revascularization of the necrotic bone with resultant abnormal joint remodeling and joint dysfunction.
• Primary cell death: Osteocyte death without other features of AVN has been seen in renal transplant patients, as well as in patients receiving steroids and those who consume significant amounts of alcohol.
• Mechanical stress: Animal studies have shown an association between increased weight bearing and an increased incidence of AVN of the femoral head.

Frequency

United States

Frequency depends on the site involved. The most common site is the hip; other locations include the carpals, talus, femur, metatarsal, mandible, and humerus. The rate of AVN of the hip is 2-4.5 cases per patient-year. In the United States, approximately 15,000 new cases are reported each year. AVN accounts for more than 10% of total hip replacement surgeries performed in the United States. Most recently, 380 cases of osteonecrosis of the jaw associated with bisphosphonate use have been reported. Most patients with osteonecrosis of the jaw also had an ongoing malignancy and/or had undergone a recent dental procedure.

International

In most countries, incidence and prevalence are unknown. A Japanese survey estimated that 2500-3300 cases of AVN of the hip occur each year; of these, 34.7% were due to corticosteroid use, 21.8% to alcohol abuse, and 37.1% to idiopathic mechanisms. A study from France reported AVN in 4.3% of allogenic bone marrow transplant recipients.

Mortality/Morbidity

Data on associated mortality rates are not available. Most data involve AVN of the hip. Mortality rates are very low and vary based on the operative procedure used to treat AVN.

Morbidity rates are high and depend on the underlying cause. Morbidity rates associated with AVN of the hip are high; the prevalence of long-term disability is significant. Despite advances in orthopedic procedures, most patients with advanced AVN require more than one hemiarthroplasty of total hip replacement during their lifetime.

Race

No racial predilection exists except for AVN associated with sickle cell disease and hemoglobin S and SC disease, which predominantly occur in people of African and Mediterranean descent.

Sex

With the exception of AVN associated with systemic lupus erythematosus, AVN is more common in men, with the overall male-to-female ratio of 8:1.

Age

AVN is a disease of middle age that most often occurs during the fourth or fifth decade of life and is bilateral in 55% of cases.

CLINICAL

Section 3 of 11  

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• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

• Avascular necrosis (AVN) may be asymptomatic and is occasionally discovered following radiography. Symptoms depend on the affected joint. Medullary infarcts are usually silent, and infarcts of the small bones of the hands and feet are often symptomatic.
• Pain in the affected joint is typically the presenting symptom, regardless of the location. Patients with AVN of the femoral head often report groin pain that is exacerbated by weight bearing. The pain may initially be mild but progressively worsens over time and with use. Eventually, the pain is present at rest and may be present at night.
• Large infarcts, such as those due to Gaucher disease and hemoglobinopathies, are associated with very severe pain.

Physical

• Initially, the physical examination findings may be unrevealing. Abnormal physical findings depend on the location and severity of disease. With progression of AVN of the hip, joint function deteriorates and the patient may walk with a limp. AVN of smaller, non–weight-bearing joints typically do not demonstrate significant disability.
• The patient may have tenderness around the affected bone.
• Both active and passive joint movements may be restricted and painful.
• A neurological deficit may be present if a nerve is affected (compressed) because of necrosis and compression deformity of affected bones.
• Advanced disease can cause joint deformity and muscle wasting.

Causes

• AVN reportedly occurs in several clinical conditions. The following etiological factors have been identified:
• • Primary or idiopathic
  • Secondary or associated with an underlying condition
  • • Trauma
    • Systemic corticosteroid use or Cushing disease
    • Alcohol abuse
    • Systemic lupus erythematosus (with or without antiphospholipid syndrome), as well as other connective tissues diseases
    • Hematologic (sickle cell disease, hemoglobinopathies)
    • Metabolic (hyperlipidemia, gout, renal failure)
    • Orthopedic disorders (slipped capital femoral epiphysis, congenital dysplasia of the hip, Legg-Calve-Perthes disease)
    • Infection (osteomyelitis, HIV)
    • Renal transplantation
    • Radiation therapy
    • Pancreatitis (uncommon)
    • Gaucher disease
    • Malignancy (marrow infiltration, malignant fibrous histiocytoma)
    • Caisson disease
    • Pregnancy

DIFFERENTIALS

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Other Problems to be Considered

Compression fracture due to osteoporosis
Inflammatory synovitis
Regional complex pain syndrome
Labral tears
Osteomyelitis
Neoplastic bone conditions

WORKUP

Section 5 of 11  

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Lab Studies

• No laboratory test findings specifically suggest or confirm the presence of avascular necrosis (AVN).

Imaging Studies

• Radiography
• • Plain radiographic findings are unremarkable in early stages of the disease. In mild-to-moderate disease, radiographs demonstrate sclerosis and changes in bone density. In advanced disease, bone deformities, such as flattening, subchondral radiolucent lines (crescent sign), and collapse of the femoral head, are evident.
• MRI
• • MRI is the most sensitive study and is the imaging procedure of choice, with an overall sensitivity of more than 90%. The specificity of MRI is also very high. The use of gadolinium is particularly useful in early detection.
  • MRI findings include decreased signal intensity in the subchondral region on both T1- and T2-weighted images, suggesting edema (water signal) in early disease. This relatively nonspecific finding is often localized in the medial aspect of femoral head. This abnormality is observed in 96% of cases.
  • The next stage is characterized by a reparative process (reactive zone) and shows low signal intensity on T1-weighted scans and high signal intensity on T2-weighted scans. This finding is diagnostic for AVN.
  • Advanced AVN is characterized by deformity of the articular surface and by calcification, which are easily detected by radiography and CT scan.
• Radionuclide bone scan
• • In early AVN, osteoblastic activity and blood flow are increased; thus, the sensitivity of radionuclide bone scan is better than that of plain films at this stage
  • The central area of decreased uptake is surrounded by an area of increased uptake. This phenomenon is known as the doughnut sign and indicates the reactive zone surrounding the necrotic area.
  • Limitations of bone scan include the following:
  • • In early AVN, bone scan is less sensitive than MRI.
    • Findings are nonspecific.
    • Results are difficult to interpret if disease is bilateral. In unilateral disease, the healthy side can be used for comparison.
• CT scan
• • CT scan shows sclerosis in the central part of femoral head as an asterisk sign.
  • Changes in the anterior part of the femoral head are easily observed.
  • CT scan is a good modality to assess the extent of the disease and calcification, but it is not as sensitive as MRI.

Procedures

• Bone biopsy can help establish diagnosis but is not routinely performed because of the availability of sensitive noninvasive tests such as MRI.

Histologic Findings

Histology is the criterion standard for diagnosis, although it is usually unnecessary. The histologic specimen is usually obtained during surgery, although it is occasionally obtained from diagnostic bone biopsy. Histologic changes are observed in both cortical bone and bone marrow.

Necrosis of cortical bone is followed by a regenerative process in surrounding tissues. Increased osteoclastic activity occurs to remove necrotic bone and increased osteoblastic activity as a reparative process.

Bone marrow lesions are usually large. Edema, hemorrhage, fibrilloreticulosis, and hypocellularity are present. Adipocytes in marrow are replaced by eosinophilic debris.

Staging

Several different staging systems have been developed and continue to be used. Ficat initially developed an AVN staging system based on radiologic findings. This staging system was revised after the widespread use of MRI in the workup of AVN. The staging system presented in the below table is based on the consensus of the Subcommittee of Nomenclature of the International Association on Bone Circulation and Bone Necrosis (ARCO: Association of Research Circulation Osseous). The most important consideration is the collapse of the femoral head cortex. Repair and complete recovery may be possible prior to collapse. Afterward, the collapse is irreversible.

Staging of Avascular Necrosis

TREATMENT

Section 6 of 11  

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Medical Care

• Medical management primarily depends on the location and severity of disease, as well as the patient's age and general health. Treatment outcomes correlate directly with the stage of the disease. No medical treatment has proven effective in preventing or arresting the disease process. In all patients, establish a firm diagnosis and exclude other conditions such as infections (osteomyelitis) and tumors. Commonly used medical measures include the following:
• • Conservative measures include limited weight bearing with crutches and pain medication. This may be beneficial and is a reasonable initial course of action if the involved segment is smaller than 15% and far from the weight-bearing region.
  • Immobilization may be helpful in some cases (eg, avascular necrosis [AVN] of the distal femur or tibia).
  • Two uncontrolled studies have shown that bisphosphonates are helpful in delaying collapse of the femoral head and thus delaying the need for surgical intervention. Longer-term data are required before this process can be completely understood and an unqualified recommendation can be made.
  • Statin therapy to prevent corticosteroid-induced AVN may be helpful. Pritchett reported a 1% incidence of AVN in 284 patients who were on statin therapy during the entire period of corticosteroid treatment (average, 7.5 y). The use of high-dose corticosteroids carries a reported 3-20% incidence of AVN.
  • In advanced disease, the disease course is unaffected by activity and will eventually require surgery.

Surgical Care

• Several surgical procedures have been tried, with variable success. No surgical procedure is the consensual best among surgeons in the treatment of AVN. In early stages of disease (precollapse), core decompression with or without bone graft is typically considered the most appropriate treatment. In late stages, characterized by collapse, femoral head deformity, and secondary osteoarthritis, total hip arthroplasty is the most appropriate treatment.
• Core decompression
• • Researchers postulate that core decompression improves circulation by decreasing intramedullary pressure and preventing further ischemia and progressive joint destruction.
  • The best results vary from 34-95%, which is significantly better than results of conservative treatment. The best results are obtained when treating patients with early disease (precollapse)
  • Core decompression is also effective for pain control.
• Bone graft
• • Bone graft options include structural cortical or medullary bone graft and vascularized bone graft with either a muscle-pedicle bone graft or free vascularized fibular graft.
  • Bone grafting is combined with the following:
  • • Core decompression, which may interrupt the cycle of ischemia
    • Excision of sequestrum, which may inhibit revascularization of the femoral head
    • Period of limited weight bearing
  • The best results have been reported with free vascularized bone grafts. Success rates of 70% and 91% have been reported in 2 small series.
  • Advantages of free vascularized grafts compared to total hip arthroplasty include the following:
  • • Healed femoral head may allow more activity.
    • No foreign body–associated complications occur.
    • If performed during early disease, lifelong survival of the femoral head is possible.
    • The patient has the option of total hip arthroplasty in the future.
  • Disadvantages of free vascularized grafts include the following:
  • • Longer period of recovery
    • Less complete pain relief
    • Variable success rate
    • Lack of effectiveness in advanced disease
• Osteotomy
• • Several osteotomy procedures have been tried with variable success.
  • Intertrochanteric osteotomies have been performed in patients with posttraumatic AVN.
  • Transtrochanteric rotational osteotomy involves rotation of the femoral head and neck on the longitudinal axis. The necrotic anterosuperior part of the femoral head becomes posterior, and the weight-bearing force is transmitted to what was previously the posterior articular surface, which is not involved in the ischemic process. In 1992, Sugano and colleagues reported excellent results in 56% of patients who underwent this procedure. Transtrochanteric rotational osteotomy is technically demanding.
• Total hip arthroplasty
• • Most patients with advanced disease (stage III and above) require total hip arthroplasty.
  • Total hip arthroplasty provides excellent pain relief for many years, although most young patients require repeat surgery.
  • With high failure rates (10-50% after 5 y), patients with AVN will probably need a second total hip arthroplasty during their lifetime.
• Other
• • AVN of the femoral condyles (knees) may respond to more conservative intervention such as arthroscopic lavage and debridement.
  • AVN of the femoral condyles has a better prognosis than hip AVN, although osteoarthritis eventually develops.

Consultations

Obtain an orthopedic consultation. Early intervention can save affected joints and obviate the need for joint replacement.

Activity

In early disease, patients should use crutches or other supports to avoid weight bearing. In advanced disease, the disease course is unaffected by activity; surgery is the only option.

MEDICATION

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No pharmaceutical treatment prevents progression of avascular necrosis [AVN]. Analgesics are needed for pain relief.

FOLLOW-UP

Section 8 of 11  

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Deterrence/Prevention

• Several precautions can be taken to minimize the risk of developing avascular necrosis [AVN] and to improve outcomes in patients with AVN.
• Use the minimum effective dose of systemic corticosteroids; when possible, use steroid-sparing agents. Statins may reduce the incidence of AVN with prolonged corticosteroid use.
• Early diagnosis and treatment are important. The earlier AVN is detected, the more treatment (and less invasive) options available to the patient.
• Provide patient education for high-risk patients, including those receiving high-dose steroids; those with Gaucher disease, those with hemoglobinopathies, and those who have undergone renal transplant.

Complications

• The natural history of AVN involves subchondral necrosis, subchondral fracture and collapse of bone, deformity of the articular surface, and osteoarthritis.
• In later stages, sclerosis and total destruction of the joint may occur.
• Nonunion of fracture and secondary muscle wasting are potential complications.

Prognosis

• Prognosis depends on the disease stage at the time of diagnosis and on any underlying conditions.
• More than 50% of patients require surgical treatment within 3 years of diagnosis.
• Half of patients with subchondral collapse of the femoral head develop AVN in the contralateral hip.
• Poor prognostic factors include the following:
• • Age older than 50 years
  • Advanced disease (stage 3 or worse) at the time of diagnosis
  • Necrosis of more than one third of the weight-bearing area of the femoral head on MRI
  • Lateral involvement of femoral head (compared to medial lesions)
  • Nonmodifiable risk factors such as cumulative dose of corticosteroids (corticosteroid-induced AVN)

Patient Education

• Patients who are at high risk should be informed about the possibility of AVN. They should be advised to report symptoms as soon as possible to facilitate early diagnosis and treatment.

MISCELLANEOUS

Section 9 of 11  

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• Miscellaneous
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Medical/Legal Pitfalls

• Patients requiring immunosuppressive therapy should take the minimum effective dose of corticosteroids for the shortest period of time possible. Alternative immunosuppressive agents should be considered. Consider the diagnosis in patients with recent onset of hip (groin) pain and normal radiography findings.
• Patients with conditions that predispose them to avascular necrosis (AVN), such as sickle cell disease or Gaucher disease, should have their treatments optimized to reduce the risk of this disorder.

MULTIMEDIA

Section 10 of 11  

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• Miscellaneous
• Multimedia
• References

Media file 1:  Avascular necrosis in the femoral head resulting from corticosteroid therapy.
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Media type:  X-RAY

Media file 2:  Avascular necrosis of the shoulder showing subchondral radiolucent lines (crescent sign).
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Media type:  X-RAY

Media file 3:  Avascular necrosis of both femoral heads. This T1-weighted image shows decreased signal intensity in both femoral heads.
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Media type:  MRI

Media file 4:  MRI of the distal femur and proximal tibia. This T2-weighted image shows increased signal intensity in the marrow.
	View Full Size Image
Media type:  MRI

REFERENCES

Section 11 of 11

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• Introduction
• Clinical
• Differentials
• Workup
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• Medication
• Follow-up
• Miscellaneous
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• References

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Article Last Updated: Oct 18, 2006