Legg-Calv-Perthes Disease. 100 years of research. Nuno Craveiro Lopes M.D.

Orthopedic Department, Garcia de Orta Hospital Almada, Portugal

Legg-Calv-Perthes disease (LCPD), was described as a individual nosological entity for nearly 100 years ago, successively in North America by Arthur Legg (1), in France by Jacques Calv (2) and in Germany by Georg Perthes (3). Until that time, several other authors had described the disease as a form of benign infection (4), or joint tuberculosis (5) as a result of a "crushing" of the epiphysis due to its vulnerability (6), as secondary to a dystrophy or congenital dislocation of the hip (7) or as a kind of vascular necrosis by micro-embolisation of unknown cause (8). After the communications of Legg, Calv and Perthes, the disease have progressively loosed its aura of mystery, in particular with the anatomic work of Zemansky (9) and the radiographic study of Waldenstrom (10), that characterized it as an avascular necrosis and described his evolutive stages of condensation, fragmentation and reconstruction, although some authors continued to doubt on the autonomy of the described lesions (11). It is still accepted the finding that Phemister made in 1921 (12): the initial event that triggers LCPD is a necrosis by ischemic events, still not perfectly understood, reaching the proximal epiphyseal nucleus, the growth plate and the metaphyseal portion of the femoral head. In fact, this region of the osteo-articular structure presents during the growth period, particularly between 3 and 11 years of age, a very poor vascular supply at the expense of cervical arteries and veins with intraarticular trajectory and terminal type distribution (13). This would facilitate its collapse in case of intra-articular effusion, traumatic or inflammatory and vicious joint positions (14). It is thought however, that children affected by the disease, have a predisposition that facilitates this type of necrosis and that genetic or metabolic factors may be involved and predispose to the existence of a lower stature (15), delayed bone age (16, 17) and bilateral lesions (18, 19). Over the past few decades, research have been developed trying to highlight the existence of these factors in the genesis of the disease, including genetic (20, 21), haematological (22, 23, 24) and metabolic (25,26), without convincing results. On the other hand, several authors have documented the existence of histological signs of bone necrosis and repair, repeated over time (27, 28, 29, 30, 31, 32, 33, 34), which suggests the possibility of repeated ischemic events in the aetiology of DLCP, with abundant documentation pointing to the existence of mechanical factors that lead to a repeated interruption of the vascular supply, such as vicious prolonged lower limb positions and repeated intra-articular effusion (35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47). Thus, according to the current concepts (32), after an initial silent period where intermittent ischemic events were produced in a variable part of the femoral epiphysis, a decrease in mechanical resistance of the epiphyseal structure lead to a subchondral pathological fracture due to microtrauma and trauma of gait and load. It is from this pathological fracture which LCPD starts and the sequence

of stages that characterize the disease begins: Collapse with formation of a sequestrum (condensation), bone resorption of the sequestrum and its replacement by granulation tissue and fibro-cartilaginous matrix (fragmentation) and reossification of fibro-cartilaginous matrix (reconstruction). During the fragmentation stage, due to bone resorption and the proliferation of granulation tissue, a pronounced deformation can be produced with extrusion out of the acetabulum of the "softened" antero-lateral area of femoral head, which was identified radiologically by LloydRoberts and Catterall (49) as a "head at risk" sign. More recently importance as a factor of better prognosis was given to the maintenance of more than 50% of the lateral height of the femoral epiphysis, the so-called "lateral column" (50, 51). In addition to the "head at risk" signs, it is known that several other factors influence a poor prognosis, especially female sex, the older age at the beginning of the disease and the extent of the lesions (52). Since the beginning of the nineteen century, specific therapeutic measures have been recommended. Schwartz in 1914 (53), recommends casting. First Waldenstrom (54) and later Danforth (55), pointed the importance of unloading in decubitus to alleviate the consequences of the disease, especially when supplemented with traction and positioning in abduction (56). Latter, in an attempt to decrease the time in decubitus, which usually extended for more than 1 year, various authors suggested different types of walking callipers and braces (57, 58). In the recent decades, several evidence based comparative studies have shown that the treatment with those callipers and braces was not effective and it have been progressively abandoned in favour of surgical treatment (59). Other means of treatment have been tried with inconsistent results, including electro-magnetic waves (60), hyperbaric oxygenation (61), anticoagulants (62), diphosphonates (63) and botulinium toxin (64). The first attempts at surgical treatment begun around 1930, based on the idea that the drilling of the necrotic bone could stimulate the vascular ingrowth, leading to a faster rebuilding process. For this purpose, Bozsan (65) proposes drilling through the trochanter and Fergusson and Howorth (66) advocate the same method by direct approach of the anterior cervical region, describing a shorter course of the disease and better final results, particularly when the intervention was carried out early. Other authors advocate curettage and graft of the neck (67) or of the epiphysis (68) with some results described as promising. However, this type of interventions eventually were abandoned on the fifties, after the introduction of recentering surgical techniques by femoral varus osteotomy, advised by Soeur (69), Craig (70) and Axer (71), which although more aggressive, were more effective in the treatment of the disease. From 1970, the publication by various authors of large series of homogeneous treatments and the confrontation of long-term results, notably by Mose (72), Meyer (73), Lauritzen (74), Loyd-Roberts, Catterall and Salomon (49) and Salter (32), allowed the definition of the objectives and indications of surgical treatment, which included varus femoral osteotomy and pelvic inonimate osteotomies: to prevent the subluxation and preserve as possible the sphericity of femoral head in order to prevent secondary arthrosis; avoid leg length discrepancy and Trendelenburg and to allow a normal gait.

Recently, multicentre studies coordinated by Herring (75), confirmed by other authors (76), establish the groups of patients which have better results receiving surgical treatment by femoral or inonimate osteotomy: patients with 8 or more years of age with B or B/C lesions. Patients with less than 8 years would have good outcome with no treatment and group C with 8 or more years of age would have bad result with any type of treatment. Research of several authors showed that in these groups, the best results of surgical treatment with femoral varus osteotomy were obtained with an early intervention in the necrotic or beginning of fragmentation stages, with a final neck-diaphyseal angle no less than 110 degrees (77). The Group of older patients (8 or more years of age) that developed lesions of worse prognosis (Herring C, in particular with hinge hip) in which surgical treatment with femoral or pelvic osteotomy was done, had poor results. The surgical option on those cases was limited to late rescue techniques, including at the level of the pelvis the Shelf and Chiary osteotomies and at the femur, valgus osteotomy and cheilectomy. This has encouraged the search for new treatment methods for this group of patients with worst prognosis, based on the principle of arthrodiastasis with external fixators, technique that have shown encouraging results (78, 79, 80, 81, 82, 83, 84, 85, 86.87). Following the ideas of Hungerford (88) and Ficat (89) about the early treatment of idiopathic femoral head necrosis in adults and based on experimental research (90, 91, 92, 93), Craveiro Lopes (94) have rehabilitated the early neck-head drilling technique for the treatment of Perthes disease, with the intention of improving the conditions of arterial supply and venous drainage and promoting the process reabsoption of necrotic bone tissue by the cutting cones and speedup of the reconstruction of the epiphyseal femoral head. The Author noted that when used early in the stage of necrosis, it leaded to a rapid reabsoption of the necrotic zone in 2 to 3 months, with a earlier onset of the reconstruction stage, on average of 4 and a half months (3 to 10 months). The reconstruction stage did not appear to be influenced by the drilling procedure. The idea of prevention of Perthes disease came after a study (95) in which the authors detected the existence of a morphotype of LCPD which includes a delay of height and weight, delayed bone age and femoral anteversion, predominantly in a child between 4 and 12 years of age, which features repeated coxalgia, aspects also referred in part by other authors (96, 97, 98, 99, 100, 101, 102). Those children had a preferred sleeping position in ventral decubitus with forced medial rotation and extension of the lower limbs, position that increases joint pressure with collapse of the cervical retinacular arteries, a fact confirmed by other authors (103, 104). At the same time, numerous authors have confirmed the hypothesis of the existence of symptomatic transient ischemic episodes without evolution to Legg-Calv-Perthes disease, what the authors called "abortive form of Perthes disease" (99, 105, 106, 107, 108, 113, 109, 110, 111, 112, 114), suggesting the existence of a possible independent pathological entity, which in certain circumstances can evolve to Legg-CalvPerthes disease. From the point of view of early diagnosis, it was demonstrated the possibility of identifying through ultrasound study, the secondary synovitis to an ischemic episode of Legg-Calv-Perthes disease, based on the type of effusion/synovitis and articular cartilage thickness (42, 43, 115, 116).

By the other side, several authors have shown the specificity and sensitivity of the Tc 99m MDP bone scan in the early diagnosis of a ischemic event of the femoral head (27, 44, 109, 117, 118, 119, 120), and later, of the superiority of nuclear magnetic resonance as regards to specificity, precocity and ability to quantify this ischemic event compared with bone scan (121, 122, 123, 124, 125, 126, 127), allowing the confirmation of the initial epiphyseal ischemic episodes that characterize the initial stage of the disease. On the basis of this data, Craveiro Lopes (92, 129) identified a new clinical entity that develops in some susceptible children, characterized by successive ischemic events in the proximal femoral epiphysis, which he called "Ischemic Disease of the Growing Hip" (IDGH), that under certain circumstances, can progress to Legg-Calv-Perthes disease. In this context, a child with IDGH, at risk of developing Legg-Calv-Perthes disease or with the disease in its early stage, particularly if its age is more than 6 years, where the prognosis of the disease is worse, Craveiro Lopes advocates the use of a Trans Neck-Head Drilling procedure (TNHD)(93, 129), in order to increase the blood supply and venous drainage of the upper femoral epiphysis, thus avoiding the repetition of ischemic episodes and preventing or aborting the appearance of Legg-Calv-Perthes disease.

CONCLUSION Presently, there are scientific indications that Legg-Calv-Perthes disease is multifactorial and caused by a combination of congenital and environmental factors. Probably the pathologic situation we know as LCPD have several aetiologies that originates a common evolution and similar manifestations. The final deformation of the femoral head is the most important prognostic factor in the long run. The worst his deformity, the greater the risk of developing osteoarthritis in the adulthood. The treatment of LCPD went through several stages. In the 1950 and 1960, the children were admitted to hospitals and placed at rest in bed for months or years, as was the case with osteoarticular tuberculosis. Between 1970 and 1980, several orthosis and braces were used, trying to restrict load on the affected limb and to prevent the collapse and deformation of the femoral head. After evidence that the results were not as expected, from 1990 surgical treatment based on osteotomies became very popular. Recent prospective studies have shown that this type of surgery is beneficial in some patients, but not in others. Evidence-based studies showed that in the group of patients with less than 6 years old and in the one with more than 8 with pronounced femoral head deformation, the surgery did not bring added value; in the first group the results are good and on the second bad with or without surgical treatment by osteotomy. By the other side, in the last decade it has become obvious that the osteotomy surgery has better result in the initial stages of the disease without deformity, situation where the use of the prognostic value of Herring classification can not be used. The controversy continues regarding the choice of the best treatment for the older group of patients. Arthrodiastasis seems to be a promising way to deal with this group of patients with worse prognosis, where the osteotomy surgery is not effective.

In the last years, it has been recognized that results of treatment may be improved with drugs. It is necessary to invest in research to better understand the biological factors involved in the aetiology and progression of the disease and develop biologically active treatments that could improve the reconstruction of a spherical femoral head and shorten the course of the disease. Finally there is evidence that the subchondral fracture that initiates the symptomatic stage of the disease, occurs in a femoral head weakened by successive multi-factorial ischemic events. The understanding of this initial stage of the disease is crucial to highlight the factors and direct the efforts to fight the disease in its prevention.

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