THE NATURAL HISTORY OF THE DISEASE
Legg-Calve-Perthes disease (LCPD) develops after interruption of the blood supply to the capital femoral epiphysis; as a consequence, part or all of the epiphysis undergoes avascular necrosis.1,2
The precise cause of LCPD still eludes us, but it is clear that a vascular insult is the final precipitating episode that leads to the disease.3–6 Studies on necropsy specimens suggest that ≥2 infarcts precede the clinical onset of LCPD.5,6 The blood supply to the capital femoral epiphysis during a period in childhood is solely from the lateral epiphyseal vessels and LCPD seems to develop at this time. Atsumi et al4 confirmed by super selective angiography that the lateral epiphyseal vessels are interrupted close to their origins in children with LCPD.
Isotope and magnetic resonance imaging scans confirm clearly that the disease is characterized by avascularity of the femoral epiphysis and they can define the extent of the epiphysis that is devoid of blood supply much before the changes of avascularity are evident on plain radiographs.7–10
The disease per se is a self-limiting disorder; the blood supply to the femoral epiphysis gets restored spontaneously. Revascularization of bone can occur by 1 of 2 mechanisms; the first is by rapid recanalization of existing vessels, which occurs within weeks, whereas the second is by formation of new vessels or neovascularization over a period of months to years.11 The pattern of revascularization by recanalization observed on an isotope scan is the appearance of a “lateral column” signifying a good prognosis, whereas neovascularization is characterized by scintigraphic appearances referred to as “base filling” and “mushrooming”, which signify a poor prognosis.11
While the vascular repair process is occurring, characteristic changes take place in the femoral epiphysis and metaphysis, the acetabulum, and the femoro-acetabular relationship as the disease evolves.
Over a period of 2 to 4 years, necrotic avascular bone of the epiphysis gets resorbed and replaced completely by new bone.2 The repair process partly entails resorption of the necrotic bone by osteoclasts and new bone deposition by the osteoblasts by a process of creeping substitution. In some areas, however, new bone does not replace the resorbed bone, but instead the granulation tissue fills regions of resorbed bone and in due course the granulation tissue is replaced by cartilage and later by bone.2,12,13
The repair process follows a sequence that can be divided into 4 stages on the basis of the appearance of the femoral head on plain radiographs: avascular necrosis, fragmentation, regeneration, and healed stages.14 The first 3 stages can be further divided into early and late parts of the respective stage (Fig. 1).15
In the stage of avascular necrosis, the epiphysis appears dense and sclerotic. A subchondral fracture that may be identified in approximately a third of children signals the extent of the underlying epiphysis that is avascular; a fracture line that extends to less than half the width of the epiphysis implies that less than half the epiphysis is infarcted.16,17 The epiphysis then loses some height and this marks the progression to the latter part of the stage of avascular necrosis.
The dense epiphysis begins to fragment and this stage is heralded by the appearance of 1 or 2 fissures in the epiphysis that run perpendicular to the surface of the epiphysis. In due course, the epiphysis appears to have broken into several pieces. During this stage, several adverse events that are associated with deformation of the femoral head may occur. The most important of these is “extrusion” of the femoral head; the anterolateral part of the avascular epiphysis comes to lie outside the acetabular margin. Extrusion commences early in the course of the disease due to hypertrophy of the articular cartilage of both the femur and the acetabulum most markedly on the medial aspect of the joint.18 Swelling and hypertrophy of the ligamentum teres may also contribute to femoral head extrusion.19 If untreated, extrusion tends to increase gradually as the disease progresses till the early part of the stage of fragmentation; shortly thereafter, there is an abrupt increase in the degree of extrusion (Table 1). Extrusion predisposes to femoral head deformation; when >20% of the width of the femoral epiphysis is extruded, there is a very high likelihood of permanent deformation of the femoral head.15,20 The propensity for deformation of the extruded femoral head has been explained on the basis of biomechanical studies.21–23
In the early stage of revascularization, new bone forms on the periphery of the necrotic epiphysis; this new woven bone is susceptible to deformation. If the lateral part of the epiphysis remains extruded at this stage, forces transmitted across the rim of the acetabulum can deform the healing epiphysis. If treatment directed at correction of femoral head extrusion is delayed, irreversible deformation of the femoral head occurs.
Gradually, mature lamellar bone replaces the dead bone and once this process is complete the disease is considered to have healed.
The duration of each of these stages of evolution of the disease varies a great deal with the duration of the earlier stages being significantly lesser than the later stages (Table 2).
During the course of the disease, osteoporosis of the metaphysis may develop and in some children a cyst may be seen in the metaphysis, abutting against the growth plate. There is no consensus on the exact nature of the underlying pathology of these metaphyseal cysts. In a magnetic resonance imaging study, 2 types of “cysts” were identified: true cysts containing water-rich fibrotic tissue and false cysts filled with granulation tissue.24 The true cysts are located in the metaphysis without any epiphyseal connection, whereas false cysts have an epiphyseal extension. Metaphyseal cysts and osteoporosis are most frequently seen during the stage of fragmentation and they resolve completely by the time the disease heals.15,24
Widening of the metaphysis is another phenomenon noted in several children; it occurs as a consequence of splaying out of the growth plate as the epiphysis flattens. Metaphyseal widening increases as the disease progresses and the timing and the rate of progression are very similar to the increase in epiphyseal extrusion (Table 3).15 The extent of metaphyseal widening correlates quite closely with the extent to which the femoral head enlarges, and greater the degree of metaphyseal widening the poorer the final outcome.15
Histologic, ultrastructural, and histochemical changes have been demonstrated in the physeal cartilage in LCPD, including a reduction in collagen and proteoglycan granules and the presence of numerous large lipid inclusions.25 In a proportion of children, premature fusion of the capital femoral growth plate occurs as a consequence of these physeal abnormalities; this results in diminished linear growth of the femoral neck. The greater trochanter continues to grow and by skeletal maturity the trochanter may outgrow the femoral neck. The foreshortened femoral neck and overriding trochanter results in altered mechanics of the hip and a Trendelenburg gait.26
Changes in the acetabulum are also seen in children with LCPD; they include articular cartilage thickening, alterations in the shape and dimensions of the acetabulum, and premature closure of the triradiate cartilage.18,27–29 Although some of these changes noted in the acetabulum are secondary to alterations in the shape and size of the femoral head, some changes are noted very early in the course of the disease and they seem to have a bearing on the outcome.
THE EFFECT OF THE AGE AT ONSET ON THE NATURAL HISTORY
The propensity for femoral head extrusion is greater in children in whom more of the epiphysis is avascular15 and it follows that the prognosis is poor in these children. Epiphyseal extrusion also tends to occur more frequently in the older child; the mean epiphyseal extrusion noted in children who were under 7 years of age at the onset of Perthes disease was 19%, whereas it was 25.6% in children >7 years.15 Extrusion almost invariably occurs at some point in the disease in children over the age of 7 years at the onset of the disease.15 In these older children, extrusion often exceeds the critical 20% by the time the disease progresses to the end of the stage of fragmentation.
In a group of older children (mean age at onset: 9 y for boys and 8.4 y for girls) who had no treatment, it was noted that only 24% had spherical femoral heads when the disease healed.15 Abnormal values of femoral head size, acetabular radius, and the articulo-trochanteric distance were noted in >90% of these children.
In the older child, if the femoral head is deformed by the time the disease heals, very little remodeling does occur between healing and skeletal maturity.30
In a small proportion of children, the disease onset is in adolescence. The disease in adolescents does not follow the pattern of evolution described earlier and often revascularization is incomplete; consequently, the outcome is uniformly poor.31–34
THE END RESULT OF UNTREATED LCPD
If LCPD is not treated, a proportion of affected hips will heal without any deformation of the femoral head; these hips function well through adult life. However, in some children, the femoral head may be enlarged (coxa magna), ovoid, or frankly deformed (coxa irregularis). The femoral neck may be short (coxa brevis) and this is associated with greater trochanteric overgrowth. The acetabulum remodels to the shape of the femoral head in the younger child so that the femoral and acetabular articular surfaces are congruent, whereas in the older child the acetabulum fails to remodel.35,36
Stulberg et al35 classified hips with the sequelae of LCPD into 5 categories on the basis of the shape and size of the femoral head and the congruence of the articular surfaces. They noted that Class I and II hips with spherical femoral heads and congruent articular surfaces had very little tendency for secondary degenerative arthritis. Class III and IV hips with ovoid or flattened femoral heads and congruent articular surfaces had a greater likelihood of developing degenerative arthritis. Class V hips, which had frankly deformed femoral heads and incongruous articular surfaces, were very likely to become arthritic prematurely.35
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