Secondary Logo

Journal Logo

Natural History of Early Onset and Late-Onset Legg-Calve-Perthes Disease

Joseph, Benjamin MD, MS Orth, MCh Orth

Journal of Pediatric Orthopaedics: September 2011 - Volume 31 - Issue - p S152–S155
doi: 10.1097/BPO.0b013e318223b423
Introduction
Free

Legg-Calve-Perthes disease develops after interruption of the blood supply to the capital femoral epiphysis. This results in various changes in the femoral epiphysis and metaphysis, the capital femoral epiphysis, growth plate, and the acetabulum. The necrotic bone of the epiphysis is gradually replaced by new bone, and over 2 to 4 years complete healing of the epiphysis occurs. The evolution of this process can be clearly seen on radiographs and the disease can be divided into distinct stages. In the early stages of the disease, the epiphysis may extrude outside the confines of the acetabulum and this predisposes to femoral head deformation.

The propensity for femoral head extrusion is greater in the older child, and consequently the likelihood of femoral deformation is higher in children who are older.

Kasturba Medical College, Manipal, Karnataka State, India

The author did not receive any financial support for this study.

The author declares no conflict of interest.

Reprints: Benjamin Joseph, MD, MS Orth, MCh Orth, Kasturba Medical College, Manipal, Karnataka State, India. e-mail: bjosephortho@yahoo.co.in.

Back to Top | Article Outline

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.

Back to Top | Article Outline

Epiphyseal Changes

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

FIGURE 1

FIGURE 1

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

TABLE 1

TABLE 1

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).

TABLE 2

TABLE 2

Back to Top | Article Outline

Metaphyseal Changes

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

TABLE 3

TABLE 3

Back to Top | Article Outline

Physeal Changes

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

Back to Top | Article Outline

Acetabular Changes

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.

Back to Top | Article Outline

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

Back to Top | Article Outline

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

Back to Top | Article Outline

REFERENCES

1. Catterall A. The natural history of Perthes' disease J Bone Joint Surg Br.. 1971;53:37–53
2. Jensen OM, Lauritzen J. Legg-Calve-Perthes' disease: morphological studies in two cases examined at necropsy J Bone Joint Surg Br.. 1976;58:332–338
3. Iwasaki K. The role of blood vessels within the ligamentum teres in Perthes' disease Clin Orthop Relat Res.. 1981;159:248–256
4. Atsumi T, Yamano K, Muraki M, et al. The blood supply of the lateral epiphyseal arteries in Perthes' disease J Bone Joint Surg Br.. 2000;82:392–398
5. Inoue A, Freeman MA, Vernon-Roberts B, et al. The pathogenesis of Perthes' disease J Bone Joint Surg Br.. 1976;58:453–461
6. Inoue A, Ono K, Takaoka K, et al. A comparative study of histology in Perthes' disease and idiopathic avascular necrosis of the femoral head in adults (IANF) Int Orthop.. 1980;4:39–46
7. Egund N, Wingstrand H. Legg-Calve-Perthes disease: imaging with MR Radiology.. 1991;179:89–991
8. de Sanctis N, Rega AN, Rondinella F. Prognostic evaluation of Legg-Calve-Perthes disease by MRI. Part I: the role of physeal involvement J Pediatr Orthop.. 2000;20:455–462
9. de Sanctis N, Rondinella F. Prognostic evaluation of Legg-Calve-Perthes disease by MRI. Part II: pathomorphogenesis and new classification J Pediatr Orthop.. 2000;20:463–470
10. Eckerwall G, Hochbergs P, Wingstrand H, et al. Magnetic resonance imaging and early remodeling of the femoral head after femoral varus osteotomy in Legg-Calve-Perthes disease J Pediatr Orthop B.. 1997;6:239–244
11. Conway JJ. A scintigraphic classification of Legg-Calve-Perthes disease Semin Nucl Med.. 1993;23:274–295
12. Catterall A, Pringle J, Byers PD, et al. A review of the morphology of Perthes' disease J Bone Joint Surg Br.. 1982;64:269–275
13. Catterall A, Pringle J, Byers PD, et al. Perthes' disease: is the epiphysial infarction complete? J Bone Joint Surg Br.. 1982;64:276–281
14. Waldenstrom H. On coxa plana. Osteochondritis deformans coxae juvenilis. Leggs disease, maladie de Calvé, Perthes krankheit Acta Chir Scand.. 1923;55:577–590
15. Joseph B, Varghese G, Mulpuri K, et al. Natural evolution of Perthes disease: a study of 610 children under 12 years of age at disease onset J Pediatr Orthop.. 2003;23:590–600
16. Salter RB, Thompson GH. Legg-Calve-Perthes disease: the prognostic significance of the subchondral fracture and a two-group classification of the femoral head involvement J Bone Joint Surg Am.. 1984;66:479–489
17. Song HR, Lee SH, Na JB, et al. Comparison of MRI with subchondral fracture in the evaluation of extent of epiphyseal necrosis in the early stage of Legg-Calve-Perthes disease J Pediatr Orthop.. 1999;19:70–75
18. Joseph B. Morphological changes in the acetabulum in Perthes' disease J Bone Joint Surg Br.. 1989;71:756–763
19. Kamegaya M, Moriya H, Tsuchiya K, et al. Arthrography of early Perthes' disease: swelling of the ligamentum teres as a cause of subluxation J Bone Joint Surg Br.. 1989;71:413–417
20. Green NE, Beauchamp RD, Griffin PP. Epiphyseal extrusion as a prognostic index in Legg-Calve-Perthes disease J Bone Joint Surg Am.. 1981;63:900–905
21. Ueo T, Tsutsumi S, Yamamuro T, et al. Biomechanical analysis of Perthes' disease using the finite element method: the role of swelling of articular cartilage Arch Orthop Trauma Surg.. 1987;106:202–208
22. Rab GT, DeNatale JS, Herrmann LR. Three-dimensional finite element analysis of Legg-Calve-Perthes disease J Pediatr Orthop.. 1982;2:39–44.
23. Rab GT. Theoretical study of subluxation in early Legg-Calve-Perthes disease J Pediatr Orthop.. 2005;25:728–733
24. Song HR, Dhar S, Na JB, et al. Classification of metaphyseal change with magnetic resonance imaging in Legg-Calve-Perthes disease J Pediatr Orthop.. 2000;20:557–561
25. Ponseti IV, Maynard JA, Weinstein SL, et al. Legg-Calve-Perthes disease: histochemical and ultrastructural observations of the epiphyseal cartilage and physis J Bone Joint Surg Am.. 1983;65:797–807
26. Shah H, Siddesh ND, Joseph B, et al. Effect of prophylactic trochanteric epiphyseodesis in older children with Perthes' disease J Pediatr Orthop.. 2009;29:889–895
27. Yngve DA, Roberts JM. Acetabular hypertrophy in Legg-Calve-Perthes disease J Pediatr Orthop.. 1985;5:416–421
28. Cho TJ, Choi IH, Chung CY, et al. The bicompartmental acetabulum in Perthes' disease: 3D-CT and MRI study J Bone Joint Surg Br.. 2005;87:1127–1133
29. Kamegaya M, Shinada Y, Moriya H, et al. Acetabular remodelling in Perthes' disease after primary healing J Pediatr Orthop.. 1992;12:308–314
30. Shah H, Siddesh ND, Joseph B. To what extent does remodeling of the proximal femur and the acetabulum occur between disease healing and skeletal maturity in Perthes disease? A radiological study J Pediatr Orthop.. 2008;28:711–716
31. Joseph B, Mulpuri K, Varghese G. Perthes' disease in the adolescent J Bone Joint Surg Br.. 2001;83:715–720
32. Specchiulli F, Cofano RE. Long-term follow-up of Perthes' disease in adolescence Chir Organi Mov.. 2001;86:7–13
33. Ippolito E, Tudisco C, Farsetti P. Long-term prognosis of Legg-Calve-Perthes disease developing during adolescence J Pediatr Orthop.. 1985;5:652–656
34. Mazda K, Pennecot GF, Zeller R, et al. Perthes' disease after the age of twelve years: role of the remaining growth J Bone Joint Surg Br.. 1999;81:696–698
35. Stulberg SD, Cooperman DR, Wallensten R. The natural history of Legg-Calve-Perthes disease J Bone Joint Surg Am.. 1981;63:1095–1108
36. Saito S, Takaoka K, Ono K, et al. Residual deformities related to arthrotic change after Perthes' disease: a long-term follow-up of fifty-one cases Arch Orthop Trauma Surg.. 1985;104:7–14
Keywords:

Perthes disease; natural history; natural evolution; disease progression

© 2011 Lippincott Williams & Wilkins, Inc.