The pathophysiological consequence of bone ischemia is avascular necrosis (osteonecrosis) or bone infarction. Interruption of the blood supply to the bone can result from acute thrombosis, trauma, an underlying vascular disease, or a predisposing osseous disorder. A process that leads to elevation of the intramedullary pressure (e.g., pyogenic infection) can impede perfusion to the point that ischemic necrosis occurs. In addition to infection, conditions that are commonly associated with ischemic bone disease in children include sickle cell disease, steroid therapy, trauma, hemophilia, irradiation, collagen vascular disease, Gaucher disease, and Cushing syndrome. Various sites in the pediatric skeleton can also be involved with idiopathic ischemic necrosis; the most common of these is the hip, that is, Legg-Calvé-Perthes disease. Ischemia in the developing epiphysis of a child can result in growth disturbance due to chondrocyte injury or death in the germinal zone of the primary physis and in the physis of the secondary ossification center. The term ischemic necrosis generally refers to involvement of an epiphysis or subarticular area, whereas bone infarct indicates the consequence of ischemia in the metaphysis or diaphysis.

The pathophysiological consequences of bone infarction tend to follow a similar sequence, irrespective of the cause of ischemia and the site of skeletal involvement. The ischemic insult leads to death of the cellular components of the bone. There is subsequent revascularization, reossification, and concomitant resorption of dead bone. The radiographic appearance of infarcted bone is indistinguishable from that of viable bone. Potential findings in this acute phase include local soft tissue swelling or osteoporosis adjacent to the necrotic bone due to disuse or hyperemia. Skeletal scintigraphy and MR allow accurate diagnosis of bone ischemia in the early, radiographically occult, phase.

Beginning several days to several weeks after the ischemic event, radiographs often show increased radiodensity in the involved portion of bone. Several mechanisms apparently contribute to this finding. As described above, there may be apparent increase in density due to regional demineralization of adjacent structures. True increased radiodensity of the ischemic bone occurs during revascularization, as new bone is laid down on residual ischemic trabeculae. Eventual resorption of the nonviable bone may result in a return to normal radiodensity. Increased density of ischemic bone can also be caused by collapse and compression of necrotic trabeculae. Focal areas of diminished radiodensity often occur in response to bone ischemia, usually due to revascularization and resorption of necrotic bone. Radiolucent areas may also occur due to fibrosis or extension of cartilage into the bone.

The earliest MR findings of bone ischemia are increased diffusion in the involved marrow and lack of normal contrast enhancement. There is often local soft tissue edema. Within a few days, marrow edema causes diminished signal on T1-weighted images and slightly elevated signal intensity on fat-suppressed T2-weighted images. The lack of contrast enhancement persists until revascularization. In the subacute to late stages, MR shows reactive changes at the margin of the bone infarct, sometimes appearing as a “double line” on fat-suppressed T2-weighted images: a high signal intensity line (hypervascular granulation) at the margin of the lesion and a parallel low signal intensity rim (reactive sclerosis). An additional early MR finding of osteonecrosis of the femoral head consists of linear subchondral bands in the epiphysis that have low signal intensity on T1-weighted images and high signal intensity on short tau inversion recovery (STIR) images. The width of these bands varies between patients. This MR finding may precede the onset of symptoms. In a minority of patients, symptoms never develop and the MR appearance normalizes.^1,2

Ischemic bone does not accumulate radiopharmaceutical on either blood pool or delayed bone scintigraphy images. Therefore, scintigraphy has a relatively specific appearance if performed early in the process. Subsequent revascularization and reactive bone formation adjacent to the ischemic focus lead to increased uptake, which is nonspecific.

Legg-Calvé-Perthes disease is an idiopathic ischemic disease of the pediatric hip. This is also termed idiopathic avascular necrosis of the hip, and is often referred to by the abbreviated term Perthes disease. The typical age range at presentation is 4 to 8 years; onset prior to 2 years or after 12 years of age is rare. Legg-Calvé-Perthes disease is more common in boys; the male-to-female ratio in patients with unilateral involvement is approximately 3:1, whereas males are affected 7 times more frequently than females when there is bilateral disease. This disorder is rare among children of African heritage. Ethnic groups with relatively high rates of occurrence include central Europeans and Japanese. There is only a very weak familial predisposition. Retardation of skeletal maturation is a consistent finding in children with Legg-Calvé-Perthes disease; the bone age frequently lags the chronological age by at least 2 standard deviations.^3,4

Bilateral involvement occurs in approximately 10% of children with Legg-Calvé-Perthes disease. Simultaneous onset of disease in the hips is uncommon with this idiopathic form of osteonecrosis. Therefore, findings of concurrent bilateral ischemic necrosis of the femoral heads suggest the presence of a specific underlying disorder, such as hypothyroidism, hemoglobinopathy, Gaucher disease, or steroid-induced osteonecrosis. Multiple epiphyseal dysplasia is also associated with radiographic findings that are similar to those of bilateral Perthes disease, but are unrelated to ischemia.

The major clinical manifestations of Legg-Calvé-Perthes disease consist of limp, pain, and limitation of motion of the affected hip. Occasionally, the pain is referred to the thigh or the medial aspect of the knee. The pain usually fluctuates, and is often more pronounced when arising in the morning and may be exacerbated by exercise. Likewise, the severity of limping tends to vary during the day. The clinical manifestations may wax and wane; many children have a history of relatively mild symptoms for days or weeks before seeking medical attention.

The fundamental pathophysiologic abnormality of Legg-Calvé-Perthes disease is osteonecrosis of the proximal femoral epiphyseal ossification center. The major blood supply to this structure is via the superior and inferior retinacular arteries. These are branches of the medial circumflex femoral artery; the lateral circumflex femoral artery supplies the greater trochanter, the anterior aspect of the femoral neck, and a small portion of the anterior aspect of the uppermost femoral epiphysis. The circumflex femoral arteries are in subperiosteal locations along the femoral neck. By the age of 8 years, these vessels become incorporated into the femoral neck. Between the ages of 4 and 7 years, there is a transitional stage of arterial development in this region, and blood supply to the femoral head is vulnerable to minor or repeated insults.

By definition, the ischemic insult to the femoral head in children with Legg-Calvé-Perthes disease is of an undetermined cause. The entire femoral epiphysis is involved. Enchondral ossification of the preossified epiphyseal cartilage temporarily ceases because of the ischemic insult; the articular cartilage, however, continues to mature, as it is nourished by synovial fluid. Growth and ossification of the bony epiphysis cease. The articular cartilage continues to proliferate, leading to cartilaginous thickening. This cartilaginous thickening is most pronounced along the medial and lateral aspects of the femoral head. This thickened articular cartilage is susceptible to small foci of necrosis in the deep layers.

In response to the ischemic insult, there is invasion of the femoral capital epiphysis by vascular granulation tissue, which replaces the epiphyseal marrow. This revascularization initiates at the periphery of the epiphysis and progressively extends centrally. Therefore, resumption of enchondral ossification initially occurs at the periphery. The healing process includes the simultaneous resorption of avascular bone and the production of new immature bone. The deposition of new bone on remaining ischemic bone trabeculae leads to an overall increase in bone mass. Both the ischemic and initial revascularization stages of Perthes disease are usually asymptomatic.

In the revascularization stage, the subchondral portion of the capital femoral epiphysis is susceptible to injury. A pathological fracture in this area causes pain, which defines the clinical onset of true Legg-Calvé-Perthes disease. The fracture typically occurs anteriorly, where the femoral head experiences the greatest degree of stress. A history of trauma or unusual physical activity is usually lacking. Structural failure of the weakened bone can also lead to collapse, with compression of trabeculae.

The clinical course of Legg-Calvé-Perthes disease varies between patients. Rarely, there is spontaneous revascularization without femoral head fracture or collapse. Other patients develop some degree of sclerosis and fragmentation, but eventually heal with no or minimal sequelae. Potential long-term changes in the hip due to Perthes disease include shortening and widening of the femoral neck, coxa plana, coxa magna, and degenerative joint disease. Leg length discrepancy is a fairly common long-term complication of Perthes disease. Most patients experience 3 phases of the disease, each lasting approximately 1.5 years: a destructive phase, a relatively stable midphase, and a healing phase.⁵

The radiographic features of Legg-Calvé-Perthes disease vary somewhat between patients. During the early, usually asymptomatic, phase of femoral head ischemia, the radiodensity and morphology of the femoral head are normal. Mild lateral displacement of the femoral head is an early manifestation of Legg-Calvé-Perthes disease that occurs in about three-quarters of patients. Potential causes of this finding include synovial thickening, joint effusion, and articular cartilage thickening. Occasionally, there is visible soft tissue prominence along the lateral margin of the hip joint due to an effusion.

A linear subchondral fracture heralds the onset of true Legg-Calvé-Perthes disease. The fracture is best visualized on a frog-leg lateral or true lateral view. The fracture usually begins at the anterior margin of the epiphysis and courses posteriorly in the subchondral zone. Some degree of flattening of the epiphysis commonly occurs in the region of the fracture. The fracture may be linear or curvilinear (Figure 61-1). The subchondral fracture is usually a transient finding, and is most often visible relatively early during the clinical course. In some children, there is no radiographically visible subchondral fracture at any time during the course of the disorder.

Generalized increase in radiodensity of the proximal epiphyseal ossification center is present in most patients with Legg-Calvé-Perthes disease. This finding often coexists with or follows the appearance of a subchondral fracture. Generalized increased density of the epiphysis is due to the deposition of new bone as well as compression of existing trabeculae. Localized sclerosis within the dome of the epiphysis is due to crushing of ischemic trabeculae. In about half of children with Perthes disease, the ossified portion of the femoral head is smaller than that of the normal, contralateral hip (Figure 61-2).

Focal radiolucencies in the metaphysis are common in patients with Perthes disease, often occurring relatively late in the process. These are usually termed metaphyseal cysts. These metaphyseal radiolucencies predominantly represent uncalcified cartilage that is derived from the adjacent growth plate. Necrosis and fibrosis can also lead to radiolucencies. The growth plate is usually widened and irregular (Figure 61-3). The femoral neck is widened and foreshortened in the later stages of the disorder. There may be premature closure of the growth plate during the healing phase. With time, collapse and remodeling of the femoral head often lead to extrusion beyond the acetabular margin and eventual development of coxa magna of variable severity (Figure 61-4).

Skeletal scintigraphy is highly sensitive for the early diagnosis of Legg-Calvé-Perthes disease. Pinhole images should be obtained for optimal depiction of femoral head anatomy. Scintigraphy may show complete femoral head ischemia despite entirely normal radiographs. As described above, however, most patients with symptomatic Perthes disease have progressed to the point that radiographic manifestations are present.

Because perfusion of bone is required for delivery of radiopharmaceutical, bone scintigraphy becomes abnormal immediately after the ischemic event. True Perthes disease requires the subsequent occurrence of degeneration and healing that are components of this disease. There are unusual instances, however, of idiopathic femoral head ischemia that reverses without progression. Reversible ischemia of the femoral head can also occur in association with transient synovitis, trauma, and septic arthritis. The secondary forms of femoral head ischemia are usually related to vascular tamponade by a joint fluid accumulation; therefore, blood pool images show a photon-deficient appearance of the hip and delayed images demonstrate diminished activity in the femoral head and adjacent growth plate. With early Legg-Calvé-Perthes disease, there is absent uptake in the femoral head on both blood pool and delayed images, but preservation of growth plate activity, as this structure is not ischemic (Figure 61-5). Normal bone scintigraphy in a patient with radiographic findings that are suggestive of Perthes disease raises the question of multiple epiphyseal dysplasia.⁶

The usual scintigraphic manifestation of the early phase of femoral head revascularization in patients with Legg-Calvé-Perthes disease is the presence of a band of activity in the lateral aspect of the epiphysis; this is termed the lateral column sign. This pattern of revascularization indicates a favorable prognosis for the long-term outcome. Revascularization also leads to increased activity in the physis and the adjacent portion of the metaphysis. These early manifestations of revascularization are usually scintigraphically visible within 4 months of the vascular insult. Over the subsequent several months, scintigraphy shows gradual return of activity on delayed images throughout the remainder of the epiphysis.^7,8

MR, as with scintigraphy, shows findings of femoral head ischemia early in the course of the process, prior to the onset of radiographic abnormalities. The MR features of otherwise uncomplicated femoral head ischemia consist of diminished signal intensity on T1-weighted images, increased signal on diffusion-weighted images, normal or increased signal intensity on T2-weighted images, and lack of normal marrow contrast enhancement. A small joint effusion is sometimes present. The subchondral fracture of true Perthes disease results in the crescent sign on MR (Figure 61-6). Synovial hypertrophy is common. Potential findings with later-stage disease include fragmentation and flattening (along the superior surface) of the epiphysis, as well as deformities of the femoral neck. Acetabular cartilage hypertrophy of the femoral head is well demonstrated with MR; acetabular cartilage hypertrophy may also occur. MR is an excellent noninvasive technique for demonstration of the adequacy of femoral head coverage by the cartilaginous extension of the acetabulum.^9–13

Conventional arthrography, CT arthrography, and MR arthrography are sometimes useful for evaluating patients with mid- or late-stage Perthes disease. Accurate depiction of femoral head extrusion beyond the acetabulum carries important prognostic and therapeutic implications. In the early stages of Perthes disease, arthrography shows mild flattening of the articular cartilage adjacent to the subchondral fracture. In the intermediate stages, the cartilaginous outline of the femoral head usually assumes an oval flattened shape. The surface of the articular cartilage remains smooth despite underlying fragmentation of the ossification center.¹⁴

Osteochondrosis refers to a focal painful osseous lesion that has radiographic findings of sclerosis and collapse. The pathophysiology may involve mechanical compression injury and/or avascular necrosis. Some forms of traction apophysitis, such as Sever disease and Osgood-Schlatter disease, may represent osteochondroses. Osteochondritis dissecans also likely represents a form of osteochondrosis (see Chapter 65). The most common locations of osteochondrosis in children include the tarsal navicular bone, the metatarsal heads, the capitellum of the humerus, and the thoracic vertebral end plates (Scheuermann disease).

In the foot, osteochondrosis of the navicular bone is termed Köhler disease. This most often is diagnosed in male children between 2 and 7 years of age. Patients may report localized pain and mild soft tissue swelling. Radiographs show the navicular bone to be narrow and sclerotic (Figure 61-7). An asymptomatic developmental variation of the navicular bone (Karp dysplasia) has a similar appearance, with delayed ossification, slow growth, flattening, and irregular sclerosis. Differentiation of this benign lesion from true osteochondrosis is by a lack of symptoms in the former, as well as a lack of progressive destruction on serial radiographs. The navicular bone in the patient with osteochondrosis is photopenic on skeletal scintigraphy during the ischemic phase. MR shows the small and hypointense ossification center to be surrounded by prominent cartilage (Figure 61-8). Lack of marrow contrast enhancement confirms ischemia during the acute phase.

Osteochondrosis of the second metatarsal head is termed Freiberg infarction or Freiberg disease. This predominantly occurs in adolescents, and is more common in girls than in boys. Similar lesions can occur in other metatarsals, particularly the third. Concomitant stress fractures are sometimes present in other bones of the foot, reinforcing the concept that repetitive stress (e.g., high heeled shoes) is involved in the pathophysiology. The pathological findings include collapse of the subchondral bone, osteonecrosis, and cartilaginous fissures.