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Legg-Calvé-Perthes DiseasePart II: Prospective Multicenter Study of the Effect of Treatment on Outcome
John A. Herring, MD1; Hui Taek Kim, MD2; Richard Browne, PhD1
1 Texas Scottish Rite Hospital for Children, 2222 Welborn Street, Dallas, TX 75129. E-mail address for J.A. Herring: tony.herring@tsrh.org
2 Department of Orthopaedic Surgery, Pusan National University Hospital, 1Ga-10, Ami-Dong, Seo-Gu, Pusan 602-739, Korea
View Disclosures and Other Information
In support of their research or preparation of this manuscript, one or more of the authors received grants or outside funding from the Texas Scottish Rite Hospital Research Fund and the Pediatric Orthopaedic Society of North America Huene Award. None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.
Investigation performed at Texas Scottish Rite Hospital for Children, Dallas, Texas

The Journal of Bone and Joint Surgery, Incorporated
J Bone Joint Surg Am, 2004 Oct 01;86(10):2121-2134
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Abstract

Background: The treatment of Legg-Calvé-Perthes disease has been based on uncontrolled retrospective studies with relatively small numbers of patients. This large, controlled, prospective, multicenter study was designed to determine the effect of treatment and other risk factors on the outcome in patients with this disorder.

Methods: We enrolled 438 patients with 451 affected hips in a prospective multicenter study in which each investigator applied the same treatment method to each of his or her patients*. The five treatment groups consisted of no treatment, brace treatment, range-of-motion exercises, femoral osteotomy, and innominate osteotomy. All patients were between 6.0 and 12.0 years of age at the onset of the disease, and none had had prior treatment. Three hundred and forty-five hips in 337 patients were available for follow-up at skeletal maturity. All hips were classified with the modified lateral pillar classification and the system of Stulberg et al.

Results: There were no differences in outcome among the hips with no treatment, those treated with bracing, and those treated with range-of-motion therapy. There were also no differences between the hips treated with a femoral varus osteotomy and those treated with an innominate osteotomy. Treatment did not have a significant effect on children who had a chronologic age of 8.0 years or less or a skeletal age of 6.0 years or less at the onset of the disease. In the lateral pillar B group and B/C border group, the outcomes of surgical treatment were significantly better than those of nonoperative treatment in children over the age of 8.0 years at the onset of the disease (p = 0.05). Patients who were 8.0 years old or less at the onset of the disease in lateral pillar group B did equally well with nonoperative and operative treatment. Hips in lateral pillar group C had the least favorable outcomes, with no differences between the operative and nonoperative groups. The lateral pillar classification (p < 0.0001) and the age at the onset of the disease (p = 0.0001) were both strong prognostic factors. Female patients did significantly worse than male patients if they were over the age of 8.0 years at the onset of the disease (p = 0.004).

Conclusions: The lateral pillar classification and age at the time of onset of the disease strongly correlate with outcome in patients with Legg-Calvé-Perthes disease. Patients who are over the age of 8.0 years at the time of onset and have a hip in the lateral pillar B group or B/C border group have a better outcome with surgical treatment than they do with nonoperative treatment. Group-B hips in children who are less than 8.0 years of age at the time of onset have very favorable outcomes unrelated to treatment, whereas group-C hips in children of all ages frequently have poor outcomes, which also appear to be unrelated to treatment.

Level of Evidence: Therapeutic study, Level II-1 (prospective cohort study). See Instructions to Authors for a complete description of levels of evidence.

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    Accreditation Statement
    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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    John A. Herring, M.D.
    Posted on December 02, 2004
    Dr. Herring responds to Dr Charalambous
    Texas Scottish Rite Hospital for Children, Dallas, TX 75129

    To the Editor:

    Dr. Charalambous notes that a number of hips may have been treated surgically prior to classification, and this was the case. The investigators in the surgical groups usually performed their procedures in the earliest stage of disease, before classification was possible, with the hope that surgery would be helpful for all hips. Only after completion of the study did the efficacy of surgery in the different subgroups become evident.

    This then raises the question of the effect of surgery on the lateral pillar classification. Is it possible that surgical treatment might change the physiology which produces the radiographic signs we use for classification? While many hips were observed to develop more severe lateral pillar collapse after early surgical intervention, some surgical influence remains a possibility. One approach to the answer is to compare the distribution of lateral pillar groups among the various treatment groups. If surgery improves the classification, there should be fewer severe hips in those groups. We found similar distributions of pillar classifications between treatment groups with one exception--there were fewer lateral pillar C hips in the innominate osteotomy group. This neither proves nor refutes the question. We have long assumed that severity was intrinsic to an affected hip, and prognosis could be determined by radiographic studies. If severity is shown to be modified by treatment, we will have to find new ways to study the efficacy of treatment. If it were true that surgery moved some C hips into a B, or B/C border classification, we would have further support for the usefulness of the surgery. Further studies will be necessary to answer this question.

    John A. Herring
    Posted on December 01, 2004
    Dr. Herring responds to Dr. Little
    Texas Scottish Rite Hospital for Children

    To the Editor:

    Dr. Little's letter raises some interesting and necessary points. He has noted that when all hips are analyzed there is not a significant difference in outcome between hips treated surgically and those treated in a brace. As Dr. Little notes, we found the most powerful prognostic indicators to be lateral pillar classification and age at onset. With this in mind, in a non-random study, one cannot rely on overall comparisons of treatment groups without segregating for the classification and age factors. Our analysis of outcome between the surgical and braced hips showed the following:

    1. No difference in outcome in patients 8 years of age or less at onset.

    2. In lateral pillar B hips over age 8 years, the braced hips had 15 Stulberg I-II (45%),14 Stulberg III (42%) and 4 Stulberg IV (12%) results, compared to 24 Stulberg I-II (73%), 7 Stulberg III (21%) and 2 Stulberg IV (6%) results in the surgically treated group, p=.079.

    3. In the B/C border group over age 8 the results were for braced hips, 2 Stulberg I-II , 2 Stulberg III, and 4 Stulberg IV outcomes vs. 0 Stulberg I-II, 8 Stulberg III, and 3 Stulberg IV for the surgical group, p=0.067. These analyses do not quite reach significance at the p=0.05 level due to the small sample sizes, but the qualitative difference are notable. From this comparison we conclude that bracing is not as effective as surgical treatment in these two lateral pillar groups with older children. (There were no differences in outcome in lateral pillar C hips between braced and surgically treated hips.)

    4. Comparisons between brace treatment and the combined range of motion and no treatment groups for the over 8 year onset and lateral pillar B, B/C, and C categories showed no notable differences between the groups with p values of 0.84, 0.35, and 0.59 respectively. We conclude from this analysis that outcome in the brace treatment group is not significantly different from that in the combined range of motion treatment and no treatment groups in older children.

    Dr. Little's "number needed to treat" analysis compared outcome between bracing and surgery for all hips, and noted that one of six patients would be improved. It is my hope that this study will begin to alter this sort of global thinking about treatment for Legg Perthes patients. Our study clearly identifies groups of patients, based on age of onset and severity classification, who are destined for a good outcome without treatment. These patients should be analyzed separately from those who have a greater likelihood of a poor outcome. We show significant advantages for the surgically treated hips of older patients with lateral pillar B and B/C border severity, and no advantage for the lateral pillar C hips. The evidence we have presented does not support universal bracing as efficacious for Legg Perthes, nor does it support any specific treatment for 65% of the hips in this study. We present evidence which supports surgical treatment for a specific group of children.

    Dr. Little's final question regarding classification after treatment brings up a familiar dilemma. While the early surgical treatment was a planned part of the study, the finding of efficacy in specific groups was an outcome determined after completion of the study. Thus we recommended a waiting period before advising surgery which was not used in the study. This is fine, but what is the surgeon to do? Should one wait for classification or should the surgery be offered at presentation to any child who is over 8 years old at onset? Based on the distribution of cases in this study, if the surgeon operated on all children over age 8, 84% would benefit, and 16% would not. While it is possible that some of the efficacy of surgery may be lost by waiting six or more months to determine the classification, we have no specific evidence to that effect.With our current state of knowledge, this issue becomes the surgeon's and patient's choice.

    Charalambos P Charalambous
    Posted on November 22, 2004
    Can we conclude that the lateral pillar classification is related to outcome in Legg-Calve-Perthes ?
    Dept of Orthopaedics, Lancaster Royal Infirmary, F.204, 159 Hathersage Road, Manchester, M13 0HX, UK

    To the Editor:

    We are writing with regards the methodology reported in the recent study by Herring, et al.(1) In it, the authors recommend that the lateral pillar classification is based on radiographs in the early fragmentation stage of Legg-Calve-Perthes disease with classification prior to early fragmentation being unreliable. The authors conclude that the lateral pillar classification group is related to the outcome of operative treatment as compared to non- operative treatment, with groups B and B/C favoured by surgery, and group C doing poorly despite the mode of treatment. Nevertheless, in 93 of 120 hips treated operatively in this study, surgery was performed in the increased density stage prior to fragmentation.

    Was the lateral pillar classification in these hips determined in the fragmentation stage and thus post surgery? Isn’t it possible that surgery in the pre- fragmentation stage could have influenced the lateral pillar height during fragmentation and thus the observed relationship of the lateral pillar group to final outcome, in particular, the failure to show any benefit of surgery for group C hips?

    1. Herring JA, Kim HT, Browne R. Legg-Calve-Perthes Disease. Part I: Classification of radiographs with use of the modified Lateral pillar and Stulberg Classifications. JBJS (Am) 2004;86: 2103-2120.

    David G Little
    Posted on November 21, 2004
    Bracing vs. Surgery in Children with LCP Disease
    The Children's Hospital at Westmead, Sydney Australia

    To the Editor:

    The paper by Herring et al in the October Journal on Legg Calve Perthes (LCP) disease is a landmark in paediatric orthopaedics. Dr Herring and the LCP study group are to be congratulated on accumulating so much data in a prospective long-term study.

    The authors have performed an expansive analysis. Sample size constraints led the authors to combine groups and conclude that operative was better than non-operative. However, if we combine bracing and surgical (containment) versus ROM and no treatment (non-containment), this is highly significant by chi square (p <_0.01 in="in" favour="favour" of="of" containment.="containment." when="when" the="the" operative="operative" and="and" bracing="bracing" groups="groups" are="are" compared="compared" there="there" is="is" no="no" significant="significant" difference="difference" _="_" though="though" sample="sample" sizes="sizes" roughly="roughly" equivalent="equivalent" _129="_129" brace="brace" _119="_119" surgery.="surgery." authors="authors" appear="appear" to="to" have="have" been="been" selective="selective" their="their" comparisons.="comparisons." by="by" logistic="logistic" regression="regression" wald="wald" chi="chi" square="square" values="values" most="most" important="important" factors="factors" were="were" classification="classification" age="age" not="not" treatment.="treatment." p="p" /> Another way to look at the effect of surgery is to examine the number needed to treat (NNT) to move a patient from one Stulberg class to another. If we compare bracing and surgery in percentage terms and accept the "best case" that surgery was superior, 7% of patients were moved from IV-V to III, and 9% from III to I-II. Thus 16% of patients moved a Stulberg grade with surgery. This gives an NNT of 6.25 - we need to operate on >6 patients to move one patient one Stulberg grade. Using this data, families should be informed when consenting for surgery that there is a 1 in 6 chance the surgery will improve their prognosis over bracing.

    The one other problem in the methodology is that most of the surgical patients were operated on before classification. We are then told to use classification and age to determine need for surgery. Is this valid?

    This is a landmark study on LCP disease but the data and conclusions remain open to interpretation and debate.

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