Practice Essentials
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 pain, loss of joint function and long-term joint damage. AVN is also known as osteonecrosis, aseptic necrosis, and ischemic bone necrosis. [1]
AVN usually involves the epiphysis (end part of a long bone), such as the femoral and humeral heads and the femoral condyles, but small bones can also be affected. In clinical practice, AVN is most commonly encountered in the hip. [1, 2] Most available data regarding the natural history, pathology, pathogenesis, and treatment of AVN pertains to femoral head necrosis.
AVN is associated with numerous conditions. Patients taking corticosteroids and organ transplant recipients are particularly at risk of developing AVN. [3, 4] AVN of the jaw has been described in patients taking bisphosphonates and, more recently, denosumab. [5, 6, 7, 8, 9] For full discussion of this entity, see Bisphosphonate-Related Osteonecrosis of the Jaw.
For diagnosis, plain radiography is the most appropriate initial imaging study, although findings are unremarkable in the early stages of AVN. MRI is the most sensitive and specific imaging modality. See Workup.
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.
Conservative measures for early AVN include limited weight bearing with crutches, and pain medications. Other measures that have been studied in early AVN include the following:
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Alendronate
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Iloprost
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Statins
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Extracorporeal shockwave therapy
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Hyperbaric oxygen therapy
Advanced AVN requires surgical treatment, with a variety of procedures being used. See Treatment.
For patient education information, see Avascular Necrosis (Aseptic Necrosis or Osteonecrosis).
Pathophysiology
Although the pathophysiology of AVN is not fully understood, the final common pathway is interruption of blood flow to the bone. AVN often affects bones with a single terminal blood supply, such as the femoral head, carpals, talus, and humerus. The earliest pathologic characteristics of osteonecrosis are necrosis of hematopoietic cells and adipocytes followed by interstitial marrow edema. [8]
Osteocyte necrosis occurs after approximately 3 hours of anoxia, but histologic signs of osteocyte death do not appear until approximately 24 to 72 hours after oxygen deprivation. [8] 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 of AVN is likely multifactorial.
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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. [10] Lipid-level–lowering drugs in animals reverse this process. Corticosteroid administration was associated with fat emboli in the femoral heads of rabbits. [11]
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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, other disorders (eg, infection, malignancy), or pregnancy.
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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.
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Primary cell death: Osteocyte death without other features of AVN has been seen in kidney transplant recipients, as well as in patients receiving steroids and those who consume significant amounts of alcohol.
Etiology
AVN may be primary or idiopathic. [12] For AVN that is secondary or associated with an underlying condition or exposure, the following factors have been identified:
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Systemic corticosteroid use or Cushing disease - The use of high-dose corticosteroids carries a reported 3-20% incidence of AVN. [3]
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Alcohol abuse
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Systemic lupus erythematosus (with or without antiphospholipid syndrome), as well as other connective-tissue diseases
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Hemoglobinopathies or hemophilic disorders (eg, sickle cell disease, hemophilia A or B)
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Osteoporosis medications (ie, bisphosphonates, denosumab)
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Hyperlipidemia
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Bone disorders (slipped capital femoral epiphysis, congenital dysplasia of the hip, Legg-Calve-Perthes disease)
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Kidney transplantation (overweight/obesity and higher cumulative corticosteroid doses are risk factors in this population [17] )
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Radiation therapy
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Gaucher disease
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Malignancy (marrow infiltration, malignant fibrous histiocytoma)
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Caisson disease (uncommon diving-related decompression illness)
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Pregnancy
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Psoriasis [19]
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Inflammatory bowel disease [20]
Epidemiology
Frequency
United States
The frequency of AVN depends on the site involved. The most common site is the hip; other locations include the carpals, talus, femur, metatarsal, mandible, and humerus. In the United States, approximately 15,000 new cases of AVN are reported each year. AVN accounts for more than 10% of total hip replacement surgeries performed in the United States. Osteonecrosis of the jaw associated with bisphosphonate has also been well studied and reported. [5, 7, 21] Most patients with osteonecrosis of the jaw also had an ongoing malignancy and/or had undergone a recent dental procedure. [21, 22, 23]
International
In most countries, the incidence and prevalence of AVN are not well reported. 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. [24]
Race-, sex-, and age-related demographics
AVN has no racial predilection except for cases associated with sickle cell disease and hemoglobin S and SC disease, which predominantly occur in people of African and Mediterranean descent.
With the exception of AVN associated with systemic lupus erythematosus, AVN is more common in men, with an overall male-to-female ratio of 8:1.
AVN is a disease of middle age that most often occurs during the fourth or fifth decade of life and is bilateral in more than half of cases.
Prognosis
The prognosis of AVN depends on the disease stage at the time of diagnosis and the presence of any underlying conditions. More than 50% of patients with AVN require surgical treatment within 3 years of diagnosis. Approximately half of patients with subchondral collapse of the femoral head develop AVN in the contralateral hip. [25]
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.
Poor prognostic factors include the following:
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Age older than 50 years
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Advanced disease (stage 3 or worse) at the time of diagnosis
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Necrosis of more than one third of the weight-bearing area of the femoral head on MRI
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Lateral involvement of femoral head (compared with medial lesions)
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Non-modifiable risk factors such as cumulative dose of corticosteroids (corticosteroid-induced AVN)
Data on mortality rates associated with AVN are not available. Most data involve AVN of the hip. Mortality rates are 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 or total hip replacement during their lifetime.
In a study that included 1706 patients who underwent total hip replacement for AVN of the femoral head, Lovecchio et al concluded that AVN is an independent risk factor for transfusion up to 72 hours postoperatively and for readmission up to 30 days postoperatively. Bleeding requiring transfusion was the most common medical complication, occurring in 19.6% of patients with AVN compared with 13.9% of those without AVN (P< 0.001). [26]
Patient Education
Patients should discuss with their primary provider if they are at risk for AVN. Patients should be advised to report joint symptoms as soon as possible to facilitate early diagnosis and treatment.
If possible, at risk patients or those with radiographic findings of AVN should be evaluated by a specialist (preferably rheumatologist or orthopedic surgeon).
For patient education information, see Avascular Necrosis (Aseptic Necrosis or Osteonecrosis).
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Avascular necrosis in the femoral head resulting from corticosteroid therapy.
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Avascular necrosis of the shoulder showing subchondral radiolucent lines (crescent sign).
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Avascular necrosis of both femoral heads. This T1-weighted image shows decreased signal intensity in both femoral heads.
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MRI of the distal femur and proximal tibia. This T2-weighted image shows increased signal intensity in the marrow.
Tables
Stage |
Clinical and Laboratory Findings |
Stage 0 |
Patient is asymptomatic. Radiography findings are normal. Histology findings demonstrate osteonecrosis. |
Stage I |
Patient may or may not be symptomatic. Radiography and CT scan findings are unremarkable. AVN is considered likely based on MRI and bone scan results (may be subclassified by extent of involvement [see below]). Histology findings are abnormal. |
Stage II |
Patient is symptomatic. Plain radiography findings are abnormal and include osteopenia, osteosclerosis, or cysts. Subchondral radiolucency is absent. MRI findings are diagnostic. |
Stage III |
Patient is symptomatic. Radiographic findings include subchondral lucency (crescent sign) and subchondral collapse. Shape of the femoral head is generally preserved on radiographs and CT scans. Subclassification depends on the extent of crescent, as follows:
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Stage IV |
Flattening or collapse of femoral head is present. Joint space may be irregular. CT scanning is more sensitive than radiography. Subclassification depends on the extent of collapsed surface, as follows:
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Stage V |
Radiography findings include narrowing of the joint space, osteoarthritis with sclerosis of acetabulum, and marginal osteophytes. |
Stage VI |
Findings include extensive destruction of the femoral head and joint. |
