Pathogenic Gene Variants Identified in Patients Presenting With Perthes or Perthes-like Hip Disorder.

AIMS: Legg-Calve-Perthes disease (LCPD) is a diagnosis of exclusion. Various conditions, such as skeletal dysplasias, can closely mimic LCPD and these must be ruled out to provide appropriate treatment, prognosis, and counseling. Traditionally, genetic testing has not been readily available in pediatric orthopaedic practice. Furthermore, the clinical value of genetic testing patients with LCPD is unclear. With the advance of next-generation sequencing (NGS) technology, genetic testing has become clinically available as a lab test. The purposes of this study were to assess the clinical utility of genetic testing in select patients with LCPD and to determine the patient characteristics of those who tested positive for skeletal dysplasia. METHODS: This is an IRB-approved, retrospective study of 63 consecutive patients who presented with Perthes-like symptoms and/or x-ray findings and who had genetic testing. The reason(s) for genetic testing included bilateral hip disease, family history of LCPD, short stature, suspected skeletal dysplasia, atypical radiographic findings, and/or combinations of these reasons. RESULTS: Of the 63 patients, 19 patients (30%) were found to have a pathogenic gene variant. In 8 of the 19, a variety of skeletal dysplasia was diagnosed. The remaining 11 patients were found to be carriers of autosomal recessive disorders. All 19 patients were referred for genetic counseling. Of the 8 patients found to have skeletal dysplasia, 3 had bilateral disease, 3 were <10 percentile in height, 1 had a family history of "LCPD," and 3 had atypical x-ray findings. In addition to the pathogenic variants, numerous genetic variants of unknown significance were found with 2 gene variants showing exactly the same variant found in 2 unrelated patients. CONCLUSIONS: With 30% of the patients showing pathogenic results, genetic testing of select patients with Perthes-like disease is valuable in detecting an underlying genetic disorder or a carrier status of a genetic disorder.

Surgeon Recommendations for Physical Activity in Patients With Pediatric Hip Conditions.

BACKGROUND: While physical activity (PA) is important during youth, it is unclear if children and adolescents with developmental dysplasia of the hip (DDH), Legg-Calvé-Perthes disease (LCPD), or slipped capital femoral epiphysis (SCFE) are expected or encouraged to return to PA once they have healed. This study examines the orthopaedic surgeons' role in advising pediatric hip patients on the PA they should engage in, assessing their practice, opinions, and consensus when making recommendations. METHODS: Orthopaedic surgeons were invited from member lists of 4 hip study groups. The survey included demographics, opinions regarding PA, and 10 case scenarios that queried respondents on the duration and intensity of PA as well as the restrictions on activity type that they would recommend for DDH, LCPD, or SCFE patients. Consensus was evaluated on a scale ranging from 0 to 1, with a value of 0 indicating no agreement among respondents and a value of 1 indicating complete agreement. RESULTS: A total of 51 orthopaedic surgeons responded. While 94% agreed that it is important for school-aged hip patients to return to PA after they have healed, 53% believed that PA may compromise the hip and contribute to the development of osteoarthritis. Average standardized consensus was 0.92 for suggesting the patient engage in some amount of PA, 0.44 for suggesting the recommended daily minimum of 60 minutes of moderate-to-vigorous physical activity (MVPA), and 0.33 for suggesting restrictions on activity type. The most frequently selected restrictions included avoiding impact activities (93%, 235/254) and contact activities (58%, 147/254), followed by weight-bearing activities (24%, 62/254). Respondents were not aware of existing PA guidelines, although 57% expressed interest in following guidelines and 39% were uncertain. CONCLUSIONS: While there is consensus among orthopaedic surgeons that children with chronic hip conditions should engage in PA, there is considerable variation when recommending the recommended daily MVPA minimum and placing restrictions on activity type. This study suggests interest among orthopaedic surgeons in developing PA guidelines that optimize outcomes for pediatric hip patients. LEVEL OF EVIDENCE: Level II-Survey study.

Does Screening Ultrasound Timing in Developmental Dysplasia of the Hip Need to be Adjusted for Moderate Preterm and Near-term Infants: A Prospective Study.

INTRODUCTION: An initial screening ultrasound is essential for patients at higher risk of developmental dysplasia of the hip (DDH) due to breech presentation or a family history of DDH. The American Academy of Pediatrics recommends screening ultrasounds to be performed after 6 weeks of age to reduce the rate of false positives. However, there is limited evidence regarding whether these screening ultrasounds need to be adjusted for gestational age in prematurity. The purpose of this study was to evaluate the influence of moderate preterm and near-term births on screening hip ultrasounds for high-risk DDH populations. METHODS: We identified all prospectively enrolled patients in a single-center database referred for screening hip ultrasound for DDH. We included those hips referred for risk factors of DDH, including breech presentation, family history of DDH, or hip click, and excluded those with known dysplasia or referral for hip instability. Each ultrasound was measured by a pediatric radiologist to determine the alpha angle and femoral head coverage. Patients were classified as "premature" if born at <37 weeks gestation or "full term" if born at ≥37 weeks gestation. All patients underwent screening hip ultrasound between 5 and 8 weeks of age. Sonographic markers of dysplasia and the incidences of abnormal ultrasound and Pavlik harness treatment were compared between cohorts. Significance was set at P <0.05. RESULTS: A total of 244 hips in 122 patients were included, 58 hips in the premature cohort and 186 hips in the full-term cohort. The premature cohort had a significantly decreased gestational age compared with the full-term cohort (35.4 ± 1.1 vs 38.5 ± 1.1 wk, respectively, P < 0.001). However, there was no difference between premature and full-term cohorts in sex distribution (69% vs 75%, females, P = 0.39), unadjusted age at the time of ultrasound (6.6 ± 0.7 vs 6.8±0.7 wk, respectively, P = 0.07), or referral reason ( P = 0.14). On hip ultrasound, there was no difference between premature and full-term cohorts with respect to alpha angle (62.6 ± 3.3 vs 62.2 ± 5.3 degrees, P = 0.41), femoral head coverage (54.9 ± 6.3 vs 55.1 ± 10.6, P = 0.19), rate of abnormal ultrasound (18.3% vs 20.7%, respectively, P = 0.68), or the rate of Pavlik harness treatment (0% vs 5.3%, respectively, P = 0.12). DISCUSSION: There was no significant difference in alpha angle or femoral head coverage between premature and full-term patients at 5 to 8 weeks of unadjusted age. This preliminary data suggests that screening ultrasounds can be performed without adjusting for prematurity. LEVEL OF EVIDENCE: Level II, prognostic study.

Patient Adherence to Wide Abduction Brace Treatment for Legg-Calvé-Perthes Disease.

BACKGROUND: A wide abduction brace called the A-frame brace is used to contain the deformed femoral head and improve femoral head remodeling in patients with Legg-Calvé-Perthes disease (LCPD). While there is some data showing the efficacy of brace treatment, little is known about patient adherence. The purpose of this study was to measure A-frame brace adherence using temperature sensors and to identify factors that influence adherence. METHODS: This is an IRB-approved retrospective study of 61 patients with LCPD treated with an A-frame brace between ages 5 and 11. Brace wear was measured using built-in temperature sensors. Pearson correlation coefficient and multiple regression were used to determine relationships between patient characteristics and brace adherence. RESULTS: Of 61 patients, 80% were male. Mean age at LCPD onset was 5.9±1.8 years and the mean age at initiation of brace treatment was 7.1±1.5 years. Fifty-eight patients (95%) were in the fragmentation or reossification stage at the start of bracing, with 23 patients (38%) having lateral pillar B, 7 (11%) lateral pillar B/C, and 31 (51%) lateral pillar C. Forty-two (69%) patients were treated with a Petrie cast for 6 weeks before the A-frame brace. Mean adherence, defined as the ratio of measured over prescribed brace wear, was 0.69±0.32. Mean adherence improved with age ( P <0.05), increasing from 0.57 in patients less than 6 to 0.84 in patients aged 8 to 11. Patients first treated with a Petrie cast had significantly better adherence than those without (0.77 vs. 0.50; P <0.005). Adherence was negatively associated with the amount of prescribed brace wear per day ( P <0.005). Adherence did not change significantly between the start and end of treatment and was not significantly associated with sex or attention deficit hyperactivity disorder. CONCLUSIONS: A-frame brace adherence was significantly associated with age at treatment, prior Petrie casting, and the amount of daily prescribed brace wear. These findings provide new insight into A-frame brace treatment, which will lead to better patient selection and counseling to optimize adherence. LEVEL OF EVIDENCE: III Therapeutic Study.

Abduction Bracing Following Anterior Open Reduction for Developmental Dysplasia of the Hip Does Not Improve Residual Dysplasia or Reduce Secondary Surgery.

BACKGROUND: Abduction bracing is commonly used following open reduction and spica casting of developmental dysplasia of the hip. However, there is little evidence to support or refute this practice that carries associated cost and burden for families. The purpose of this study was to determine the efficacy of abduction bracing after open reduction in improving the acetabular dysplasia and reducing the rate of secondary surgery for residual dysplasia. METHODS: This is a retrospective study of patients treated with open reduction at a single tertiary referral center. Demographic data, severity of dislocation [International Hip Dysplasia Institute (IHDI) class], age at reduction, and casting duration were obtained. Patients were prescribed no bracing, part-time (≤18 h/d), or full-time (≥20 h/d) brace wear based on surgeon preference. Acetabular index (AI) measurements were obtained at cast removal and at 2- and 4-year follow-up. RESULTS: A total of 146 hips underwent open reduction with 61% (89/146) of hips treated with abduction bracing. There was no difference between braced and nonbraced cohorts with regards to sex, age at time of reduction, dislocation severity, cast duration, immediate postcasting AI, or incidence of medial open reduction. There was no difference in hips treated with or without brace following open reduction with regards to AI at 2 years postreduction (31.8±6.7 vs. 30.4±6.1 degrees, P =0.27) or at 4 years postreduction (24.9±6.5 vs. 24.7±6.5 degrees, P =0.97). However, further analysis showed lower mean AI at 2-year follow-up for braced versus nonbraced patients following medial open reduction (30.0±5.7 vs. 34.5±7.0 degrees, P =0.02). This difference was no longer present at 4-year follow-up (26.6±6.8 vs. 24.2±6.6 degrees, P =0.44). However, 4/19 (21%) nonbraced hips underwent secondary surgery for residual dysplasia and were consequently excluded from the AI measurement at 4 years postreduction (compared with 4/39 [10%] braced hips within the same time period). There was no difference in the rate of secondary surgery between braced and nonbraced hips (30% vs. 33%, respectively, P =0.70). Multivariate analysis demonstrated that neither IHDI classification, bracing, nor age at reduction predicted residual dysplasia. CONCLUSIONS: Abduction bracing following anterior open reduction for developmental dysplasia of the hip is not associated with decreased residual dysplasia at 2/4 years postreduction or with decreased secondary surgery. These results suggest that abduction bracing following anterior open reduction may not provide clinical benefit. However, abduction bracing may be beneficial following medial open reduction. A prospective study is necessary to provide more definitive recommendations. LEVEL OF EVIDENCE: Level III-therapeutic study.

Do Weightbearing Restrictions Cause Excess Weight Gain in Children With LEGG-Calvé-Perthes Disease?

BACKGROUND: Restricted weight bearing is commonly prescribed in Legg-Calvé-Perthes Disease (LCPD), raising concerns of causing overweight or obesity. This study utilizes prospectively collected data to address the following questions: (1) does body mass index (BMI) Z-score increase over the course of LCPD follow-up; (2) is having a BMI category of normal, overweight, or obese at baseline associated with BMI Z-score changes over the course of follow-up; and (3) is the duration of weight bearing restrictions (no restrictions, <3, 3 to <6, 6 to 9, or >9 mo) associated with BMI Z-score changes. METHODS: Data of 130 children aged 5 to 12 years with unilateral early-stage LCPD were extracted from an international database. Nation-specific BMI Z-scores and percentile-based weight categories were determined, and the duration of follow-up and weight bearing restrictions were calculated. Longitudinal changes in BMI Z-scores were evaluated for the 3 study questions using mixed effects linear regression models with surgery as a covariate. Sensitivity analyses were used to determine the influence of socio-cultural background (USA vs. India) for each study question. RESULTS: During the 35.5±15.9 months of follow-up, no statistically significant increase in BMI Z-scores was observed across the entire cohort, or following stratification by baseline weight categories or the duration of the weight bearing restriction. Sensitivity analyses indicated that patients in the USA had no change in their BMI Z-score. When stratified by weight categories, the normal weight of US children had a small increase in their BMI Z-score (0.005 per mo, 95% confidence interval: 0.0002, 0.009), but this was not seen in other BMI categories. The cohort of Indian children had a small but significant decrease in their BMI Z-score (-0.005/mo, 95% CI: -0.009, -0.0002). After stratification by weight categories, a small decrease of the BMI Z-score was observed only in the Indian overweight children (-0.016 per mo, 95% CI: -0.027, -0.005) and no other BMI category. CONCLUSIONS: Weightbearing restrictions over the course of follow-up for our cohort of children with early-stage LCPD were not associated with clinically meaningful increases of BMI Z-scores. Weight gain is multi-factorial and probably not caused by weight bearing restrictions alone. LEVEL OF EVIDENCE: III Diagnostic Study.

The Significance of Isolated Hip Click as a Sign of DDH: Implications on Referral Guidelines.

BACKGROUND: The clinical significance of an isolated hip click remains unclear. The rates of developmental dysplasia of the hip (DDH) in those referred for hip click vary from 0% to 28%. The purpose of this study was to evaluate the rate of DDH in patients prospectively referred for isolated hip click. METHODS: We prospectively enrolled patients referred to a single pediatric orthopaedic center with concern for DDH secondary to isolated hip click felt by the pediatrician on examination. Patients with known sonographic abnormalities or risk factors for DDH (breech presentation or positive family history) were excluded. Ultrasounds were obtained upon initial presentation and defined as abnormal if alpha angle <60 degrees and/or femoral head coverage (FHC) <50%. Mild dysplasia, analogous to Graf IIa physiological immaturity, was defined as alpha angle 50<α<60 and/or <50% FHC in a patient <3 months age. Severe dysplasia was defined as ≤33% FHC, which has been proposed to be sonographically consistent with a hip dislocation. RESULTS: Two hundred fifty-five children were referred for isolated hip click. One hundred eighty-nine patients (74%) had normal ultrasound whereas 66 patients (26%) had sonographic abnormalities (mean age 6.5±6.2 wk at initial ultrasound). Fifty patients (19.6%) demonstrated physiological immaturity, 3 patients (1.2%) demonstrated moderate sonographic dysplasia, and 13 patients (5.1%) had sonographic findings consistent with severe dysplasia or dislocated hip. Hips with severe dysplasia were younger than the remaining population (2.8±2.4 wk vs. 6.6±6.2 wk, P <0.001) with no difference in sex distribution ( P =0.07) or first-born birth order ( P =0.36). For those with sonographic abnormality, 18 (27%) patients were treated with Pavlik harness, 1 (2%) was treated with abduction orthosis, and the remainder (71%) were observed for resolution of physiological immaturity. CONCLUSIONS: Infants with isolated hip click identified by their pediatrician may have higher rates of dysplasia than previously reported. We recommend screening ultrasound and/or orthopaedic referral for all infants with isolated hip click. LEVEL OF EVIDENCE: Level II-prospective prognostic study.

Moderate Weightbearing Restrictions Are Associated with Worse Depressive Symptoms and Anxiety in Children Aged 5 to 7 Years with Perthes Disease.

BACKGROUND: Perthes disease most commonly affects children 5 to 7 years old, and nonoperative management, such as weightbearing and activity restrictions, is generally recommended. In earlier research in children aged 8 to 14 years who had Perthes disease, we found that the restrictions were associated with worse mobility, but mental health or social health measures were not linked. However, Perthes disease most commonly affects children 5 to 7 years old who are more emotionally and cognitively immature. Children in this age group are beginning school and organized sports experiences while developing meaningful social relationships for the first time. Because of such different life experiences, it is important to understand the psychosocial consequences of weightbearing and activity restrictions on this specific age group, as they may help guide choices about weightbearing restrictions and mental health support. QUESTIONS/PURPOSES: In patients aged 5 to 7 years with Perthes disease, we asked: (1) Are weightbearing and activity restrictions associated with worse mental health, evaluated with the Patient-reported Outcome Measurement Information System (PROMIS) depressive symptoms, anxiety, and anger questionnaires? (2) Are weightbearing and activity restrictions associated with worse social health (PROMIS peer relationships measure)? (3) Are weightbearing and activity restrictions associated with worse physical health measures (PROMIS mobility, pain interference, and fatigue measures)? (4) What other factors are associated with mental, social, and physical health measures in these patients? METHODS: Data were collected from 97 patients with a diagnosis of Perthes disease. Inclusion criteria were age 5 to 7 years at the time the PROMIS was completed, English-speaking patients and parents, in the active stage of Perthes disease (Waldenstrom Stages I, II, or III) who were recommended weightbearing and activity restrictions because of worsening hip pain, poor hip ROM, femoral head deformity, as a postoperative regimen, or if there was substantial femoral head involvement on MRI [23]. Based on their weightbearing and activity restriction regimen, patients were categorized into one of four activity restriction groups (no, mild, moderate, and severe restriction). The following pediatric parent-proxy PROMIS measures were obtained: depressive symptoms, anxiety, anger, peer relationships, mobility, pain interference, and fatigue. We excluded five patients who did not meet the inclusion criteria. Of the remaining 92 patients, 21 were in the no restriction group, 21 were in the mild restriction group, 28 were in the moderate restriction group, and 22 were in the severe restriction group at the time of PROMIS administration. ANOVA was used to compare differences between the mean PROMIS T-scores of these four groups. T-scores are computed from PROMIS survey responses, and a T-score of 50 represents the age-appropriate mean of the US population with an SD of 10. A higher T-score means more of that measure is being experienced and a lower score means less of that measure is being experienced. To address the possibility of confounding variables such as Waldenstrom stage, gender, age at diagnosis, and history of major surgery, we performed a multivariable analysis to compare the association of different weightbearing regimens and the seven PROMIS measures. This allowed us to answer the question of whether weightbearing and activity restrictions are associated with worse physical, mental, and social health measures in Perthes patients aged 5 to 7 years, while minimizing the possible confounding of the variables listed above. RESULTS: After controlling for confounding variables such as Waldenstrom stage, gender, age at diagnosis, and history of major surgery, we found that moderate activity restriction was associated with worse depressive symptoms (ß regression coefficient = 6 [95% CI 0.3 to 12]; p = 0.04) and anxiety (ß = 8 [95% CI 1 to 15]; p = 0.02) T-scores than no restrictions. The mild (ß = -7 [95% CI -12 to -1]; p = 0.02), moderate (ß = -15 [95% CI -20 to -10]; p < 0.001), and severe (ß = -23 [95% CI -28 to -18]; p < 0.001), restriction groups had worse mobility T-scores than the no restriction group. Weightbearing and activity restrictions were not associated with anger, peer relationships, pain interference, and fatigue measures. Waldenstrom Stage II disease was associated with worse pain interference than Waldenstrom Stage III (ß = 7 [95% CI 0.4 to 13]; p = 0.04). A history of major surgery was associated with worse anger scores (ß = 18 [95% CI 3 to 33]; p = 0.02). The child's gender and age at diagnosis had no association with any of the seven PROMIS measures. CONCLUSION: Moderate weightbearing and activity restrictions are associated with worse depressive symptoms and anxiety in patients with Perthes disease aged 5 to 7 years, after controlling for Waldenstrom stage, gender, age at the time of diagnosis, and history of surgery. Considering the discoveries in this study and in our previous study, for patients 5 to 7 years old, we recommend that providers discuss the potential for mental health changes with moderate weightbearing restrictions with patients and their families. Furthermore, providers should monitor for worsening mental health symptoms at each follow-up visit and refer patients to a clinical child psychologist for support when appropriate. Future studies are needed to assess the effects of these restrictions on mental health over time and after patients are allowed to return to normal activities. LEVEL OF EVIDENCE: Level III, therapeutic study.

The Role of the Artery of Ligamentum Teres in Revascularization in Legg-Calve-Perthes Disease.

INTRODUCTION: A recent cadaveric study supported that most immature hips are supplied by the artery of ligamentum teres and suggested this medial vascular source may influence the pattern of revascularization in Legg-Calve-Perthes disease (LCPD). The purposes of this study were to characterize the perfusion pattern of the capital femoral epiphysis and determine the role of the artery of ligamentum teres in early revascularization of LCPD. METHODS: Retrospective review of perfusion magnetic resonance imaging (pMRI) from 64 hips in early stage LCPD (Waldenström stage I to IIa) was performed. Two independent graders categorized perfusion pattern based on the presence of perfusion medially (from artery of ligamentum teres) and/or laterally (from the medial femoral circumflex artery) on coronal and sagittal MRI series: type 1-lateral perfusion only, type 2-separate medial and lateral perfusion, or type 3-coalescent medial and lateral perfusion. Lateral pillar classification was obtained for hips that reached mid-fragmentation. RESULTS: We identified 64 patients (75% male) with mean age at diagnosis of 8.5±2.1 years. 36% (23/64) hips underwent pMRI during stage I and 64% (41/64) during stage IIa. pMRI revealed separate and distinct medial and lateral sources of perfusion (type 2) in 50% (32/64) hips. In stage I, the distribution of type 1/2/3 hips was found to be 26%/52%/22%. However, in stage IIa there was a nonsignificant trend toward greater coalescence of the medial and lateral perfusion with a distribution of type 1/2/3 of 7%/49%/44% (P=0.07). There was a nonsignificant trend toward weak negative linear correlation between lower initial perfusion grade and worsened lateral pillar classification at mid-fragmentation (r=-0.25, P=0.05). CONCLUSION: The presence of separate and distinct areas of perfusion of medial and lateral capital femoral epiphysis provides further evidence of the role of the ligamentum teres vessels in revascularization during the early stages of LCPD. The changes in perfusion pattern with disease progression likely reflect that medial femoral circumflex artery and ligamentum teres vessel revascularization occur separately, but ultimately coalesce posteriorly over time. LEVEL OF EVIDENCE: Level II-prognostic study.

The Clinical Significance of Infolded Limbus on Postreduction Arthrogram in Developmental Dysplasia of the Hip.

BACKGROUND: The purpose of this study was to investigate whether presence of an infolded limbus on hip arthrogram at index closed reduction was associated with increased residual dysplasia or secondary surgery. METHODS: We retrospectively reviewed all patients who underwent closed reduction for dysplasia of the hip with a minimum 2-year follow-up between 1980 and 2016. Demographic data was obtained including the age at reduction and severity of dislocation based on the International Hip Dysplasia Institute (IHDI) classification. Arthrograms performed at time of closed reduction were separately reviewed by 3 fellowship-trained pediatric orthopaedic surgeons to evaluate for an infolded limbus. The primary radiographic outcome was acetabular indices at 2 and 4 years postreduction. We also assessed the presence of avascular necrosis and rate of secondary reconstructive surgery for residual dysplasia. RESULTS: A total of 182 hips in 165 patients underwent closed reduction at a mean age of 9.8±4.5 mo and were followed a mean of 9.0±4.9 y. An infolded limbus was identified in 20.3% (37/182) hips with substantial agreement among the 3 graders (Fleiss κ=0.75). The frequency of labral infolding increased with the severity of dislocation (8.8%% of IHDI II, 26.7% IHDI III, and 25.0% of IHDI IV hips; P=0.03). Hips with infolded limbus were older at reduction (12.4±5.3 vs. 9.2±5.8 mo, P=0.001). The mean acetabular index was higher in hips with infolded limbus than hips without at 2 years postreduction (34.8±4.8 vs. 32.6±5.8 degrees, respectively; P=0.04). However, multivariate analysis revealed that only the severity of dislocation predicted dysplasia at 2 years postreduction. No significant difference in acetabular index was seen at 4 years postreduction (27.2±7.4 vs. 25.4±6.5 degrees, P=0.24). There was no difference in avascular necrosis between groups (P=0.74). There was no difference in rate of secondary surgery between hips with labral infolding and those without (35% vs. 30%, respectively; P=0.52). CONCLUSIONS: An infolded limbus was more common in older patients with more severe dislocations. However, it is not associated with increased residual dysplasia or secondary surgery and may have limited utility in decision-making during closed reduction. LEVEL OF EVIDENCE: Level II-prognostic study.

Does the Deformity Index Reliably Predict the Shape of the Femoral Head at Healing of Legg-Calvé-Perthes Disease?

BACKGROUND: Treatment of Legg-Calvé-Perthes disease (LCPD) aims to preserve the spherical shape of the femoral head. The deformity index (DI) <0.3, measured 2 years from disease onset, is a surrogate measure that predicts that the femoral head will be Stulberg class I or II at skeletal maturity. There is no study that compares the predictive value of DI against a quantitative measure of the shape of the femoral head when the disease heals. We undertook this study to assess the reproducibility of a new method of measurement of DI and see if DI could predict the shape of the femoral head when the disease healed. METHODS: DI was measured 2 years after disease onset and the Sphericity Deviation Score (SDS) was measured at healing of LCPD on radiographs of 43 children. Reproducibility of measurement was tested. Each healed femoral head was classified as spherical or aspherical based on subjective visual assessment. The DI values were compared with SDS values. RESULTS: The reproducibility of measurement of SDS was excellent and superior to that of DI. The mean duration of disease was 3.97±0.96 years. Only 17 of 32 hips with DI values <0.3 at 2 years had spherical femoral heads at healing (SDS <10). Three hips with SDS values <10 had DI values >0.3. The positive and negative predictive values of a DI <0.3 in predicting if the femoral head will be spherical (SDS <10) when the disease healed were 53% and 73%, respectively. CONCLUSION: Though DI can be reproducibly measured the predictive value of a DI <0.3, to accurately identify hips that are likely to heal with spherical femoral heads, is not sufficiently high to justify its use as an outcome measure.

Interobserver and Intraobserver Reliability in the Salter Classification of Avascular Necrosis of the Femoral Head in Developmental Dysplasia of the Hip.

BACKGROUND: Avascular necrosis (AVN) of the femoral head is a concerning complication that can result from treatments for developmental dysplasia of the hip (DDH). AVN can lead to degenerative osteoarthritis, persistent acetabular dysplasia, reduced function, and continuing hip pain. The incidence of AVN reported in the DDH literature is widely varied (0% to 73%). This variability may arise from lack of consensus on what constitutes true AVN in this patient population, and lack of clear criteria provided in studies reporting incidence rates. METHODS: A multicentre, prospective database of infants diagnosed with DDH between 2010 and 2014 from 0 to 18 months of age was analyzed for patients treated by closed reduction (CR). Twelve pediatric orthopaedic surgeons completed 2 rounds of AVN assessments. Deidentified anteroposterior radiographs at most recent follow-up were provided to surgeons along with patient age at radiographic assessment, length of follow-up, ands affected hip. Ten of 12 surgeons completed a third round of assessments where they were provided with 1 to 2 additional radiographs within the follow-up period. Radiographic criteria for total AVN described by Salter and colleagues were used. Surgeons rated the presence of AVN as "yes" or "no" and kappa values were calculated within and between rounds. RESULTS: A total of 69 hips in 60 patients were assessed for AVN a median of 22 months (range: 12 to 36) post-CR. Interobserver kappa values for rounds 1, 2, and 3 were 0.52 (range: 0.11 to 0.90), 0.61 (range: 0.21 to 0.90), and 0.53 (range: 0.10 to 0.79), respectively. Intraobserver agreement for AVN diagnosis was an average of 0.72 (range: 0.31 to 0.96). CONCLUSIONS: Despite using the most commonly referenced diagnostic criteria, radiographic diagnosis of AVN following CR in DDH patients demonstrated only moderate agreement across surgeons. The addition of sequential radiographs did not improve cross-observer reliability, and while substantial agreement was seen within observers, the range of intraobserver kappa values was large. LEVEL OF EVIDENCE: Level I-diagnostic study.

Expanding the phenotypic spectrum of RPL13-related skeletal dysplasia.

RPL13-related disorder is a newly described skeletal dysplasia characterized as a form of spondyloepimetaphyseal dysplasia with normal birth length, early postnatal growth deficiency, severe short stature, and genu varum. We present a 9-year-old male with a history of lower leg pain and concern for an unspecified form of multiple epiphyseal dysplasia (MED). Exome sequencing revealed a de novo heterozygous RPL13 c.477+1G>A (IVS4+1G>A) pathogenic variant. This is the first identified case of an individual with an RPL13-related skeletal dysplasia, normal height, and radiographs consistent with a form of MED and Legg-Calve-Perthes-like disease. This case expands the phenotype of RPL13-related disorders.

Weightbearing and Activity Restriction Treatments and Quality of Life in Patients with Perthes Disease.

BACKGROUND: Weightbearing and activity restrictions are commonly prescribed during the active stages of Perthes disease. These restrictions, ranging from cast or brace treatment with nonweightbearing to full weightbearing with activity restrictions, may have a substantial influence on the physical, mental, and social health of a child. However, their impact on the patient's quality of life is not well-described. QUESTIONS/PURPOSES: After controlling for confounding variables, we asked (1) are restrictions on weightbearing and activity associated with physical health measures (as expressed by the Patient-Reported Outcome Measurement Information System [PROMIS] mobility, PROMIS pain interference, and PROMIS fatigue) of children in the active stages of Perthes disease? (2) Are these restrictions associated with poorer scores for mental health measures (PROMIS depressive symptoms and PROMIS anxiety)? (3) Are these restrictions associated with poorer scores for social health measures (PROMIS peer relationships)? METHODS: Between 2013 and 2020, 211 patients with Perthes disease at a single institution were assigned six PROMIS measures to assess physical, mental, and social health. Patients who met the following eligibility criteria were analyzed: age 8 to 14 years old, completion of six PROMIS measures, English-speaking, and active stage of Perthes disease (Waldenstrom Stage I, II, or III). Weightbearing and activity restrictions were clinically recommended to patients in the initial through early reossification stages of Perthes disease when patients had increasing pain, loss of hip motion, loss of hip containment, progression of femoral head deformity, increased hip synovitis, and femoral head involvement on MRI or as a postoperative regimen. Patients were categorized into four intervention groups based on weightbearing and activity regimen. We excluded 111 patients who did not meet the inclusion criteria. The following six pediatric self-report PROMIS measures were assessed: mobility, pain interference, fatigue, depressive symptoms, anxiety, and peer relationships. Of the 100 patients, 36 were categorized into the no-restriction regimen, 27 into the mild-restriction regimen, 25 into the moderate-restriction regimen, and 12 into the severe-restriction regimen at the time of PROMIS administration. The median (range) age at diagnosis was 8 years old (range 2 to 13 years). There were 85 boys and 15 girls. Eleven patients had hips in Waldenstrom Stage I, 10 were in Stage II, and 79 were in Stage III. Forty-four patients had hips classified as lateral pillar B and 47 patients as lateral pillar C. Nine patients had not reached the mid-fragmentation stage for appropriate lateral pillar classification by the time they took the PROMIS survey. ANOVA was used to compare differences between the mean PROMIS T-scores of these weightbearing/activity regimens. Results were assessed with a significance of p < 0.05 and adjusted for Waldenstrom stage, gender, age at diagnosis, and history of major surgery using multivariate regression analysis. RESULTS: After controlling for confounding variables, the mild- (ß regression coefficient -15 [95% CI -19 to -10]; p < 0.001), moderate- (ß -19 [95% CI -24 to -14]; p < 0.001), and severe- (ß -25 [95% CI -30 to -19]; p < 0.001) restriction groups were associated with worse mobility T-scores compared with the no-restriction group, but no association was detected for the pain interference or fatigue measures. Weightbearing and activity restrictions were not associated with mental health measures (depressive symptoms and anxiety). Weightbearing and activity restrictions were not associated with social health measures (peer relationships). Earlier Waldenstrom stage was associated with worse pain interference (ß 10 [95% CI 2 to 17]; p = 0.01) and peer relationships scores (ß -8 [95% CI -15 to -1]; p = 0.03); female gender was linked with worse depressive symptoms (ß 7 [95% CI 2 to 12]; p = 0.005) and peer relationships scores (ß -6 [95% CI -12 to 0]; p = 0.04); and earlier age at diagnosis was associated with worse peer relationships scores (ß 1 [95% CI 0 to 2]; p = 0.03). History of major surgery had no connection to any of the six PROMIS measures. CONCLUSION: We found that weightbearing and activity restriction treatments are associated with poorer patient-reported mobility in the active stages of Perthes disease after controlling for Waldenstrom stage, gender, age at diagnosis, and history of surgery. Weightbearing/activity restrictions, however, are not associated with pain interference, fatigue, depressive symptoms, anxiety, and peer relationships. Understanding how these treatments are associated with quality of life in patients with Perthes disease can aid in decision-making for providers, help set expectations for patients and their parents, and provide opportunities for better education and preparation. Because of the chronic nature of Perthes disease, future studies may focus on longitudinal trends in patient-reported outcomes to better understand the overall impact of this disease and its treatment. LEVEL OF EVIDENCE: Level III, therapeutic study.

Reproducibility of Radiographic Measurements Made in the Active Stages of Legg-Calvé-Perthes Disease: Evaluation of a Prognostic Indicator and an Interim Outcome Measure.

BACKGROUND: Deformity index (DI) and extrusion index (EI) are 2 radiographic methods currently used to quantify femoral head deformity in the active stages of Legg-Calvé-Perthes disease. This study aimed to quantify the interobserver reproducibility of the 2 methods using a large, international group of pediatric orthopaedic surgeons with diverse clinical experience. METHODS: Radiographs of patients (age 6 to 11 y at time of diagnosis) prospectively enrolled in an international multicenter-cohort study, were measured by members of our study group. For each radiograph, the raters independently assessed EI (n=33 cases) and DI (n=32 cases), along with the rater's subjective assessment of the extent of hip deformity (ie, none, mild, moderate, or severe). Reliability analysis was conducted using intraclass correlation coefficient (ICC) and κ techniques. RESULTS: The ICC for EI on the affected side was 0.68 (95% confidence interval: 0.57-0.79). The calculated DI ICC was 0.53 (95% confidence interval: 0.41-0.68). Subjectively, an average of 68±3.5% of surgeons agreed on the subjective description of each patient's femoral head deformity. CONCLUSIONS: EI is measured with a reasonably high rate of correlation among surgeons from disparate backgrounds. Agreement is lower among the same group of surgeons when the more complex DI is used. DI is most useful when utilized by a small number of experienced observers in a research setting, whereas EI may have better clinical applicability. LEVEL OF EVIDENCE: Level III-reliability study.

Reliability and Validity of Visual Estimation of Femoral Head Hypoperfusion on Perfusion MRI in Legg-Calve-Perthes Disease.

BACKGROUND: Assessing the severity of Legg-Calve-Perthes disease is important for treatment decision-making and determining prognosis. Perfusion magnetic resonance imaging (MRI) scans have improved our ability to assess femoral head hypoperfusion, and the use of an image analysis software called HipVasc (Scottish Rite for Children, Dallas TX) has allowed precise quantification for research purposes. In the clinical setting, using HipVasc software is not practical, and visual estimation is used to assess hypoperfusion. Currently, the reliability of visual estimation is unknown. The purpose of this study was to determine the reliability and validity of visual estimation of hypoperfusion on perfusion MRI and compare the results to measurements obtained with the HipVasc software. METHODS: Fourteen pediatric orthopaedic surgeons, divided into 4 groups, participated in this study. Each surgeon completed a 30-minute in-person training on HipVasc before proceeding. Stratified by category of severity, 122 MRIs were randomly assigned to 1 of the 4 groups so that each group member measured the same set of ∼30 MRIs. Each surgeon documented their visual estimation of hypoperfusion first, then used HipVasc to measure the hypoperfusion and recorded their results. Interobserver reliability was assessed at the group level by calculating the intraclass correlation coefficient. RESULTS: Good correlation and reliability was found between the visual estimate and HipVasc measurements with an overall mean intraclass correlation coefficient of 0.87 and mean Pearson coefficient of 0.90. The mean interobserver reliability of visual estimation was 0.84. Observers had a tendency to overestimate hypoperfusion with visual estimation. CONCLUSIONS: This study demonstrates the reliability and validity of visual estimation as a clinically applicable method for determining femoral head hypoperfusion. Our study is the first to measure the reliability of visual estimation and HipVasc with a large cohort of clinicians, specifically pediatric orthopaedic surgeons with varied experience in graphical software analysis. We recommend using visual estimation as a clinically applicable method to make treatment decisions, and its accuracy is comparable to HipVasc software analysis. LEVEL OF EVIDENCE: Level III-diagnostic.

Hip Morphology in Early-stage LCPD: Is There an Argument for Anatomic-specific Containment?

BACKGROUND: Early containment surgery has become increasingly popular in Legg-Calvé-Perthes Disease (LCPD), especially for older children. These procedures treat the proximal femur, the acetabulum, or both, and most surgeons endorse the same surgical option regardless of an individual patient's anatomy. This "one-surgery-fits-all" approach fails to consider potential variations in baseline anatomy that may make one option more sensible than another. We sought to describe hip morphology in a large series of children with newly diagnosed LCPD, hypothesizing that variation in anatomy may support the concept of anatomic-specific containment. METHODS: A retrospective review of a prospectively collected multicenter database was conducted for patients aged 6 to 11 at diagnosis. To assess anatomy before significant morphologic changes secondary to the disease itself, only patients in Waldenström stages IA/IB were included. Standard hip radiographic measurements including acetabular index, lateral center-edge angle, proximal femoral neck-shaft angle (NSA), articulotrochanteric quartiles, and extrusion index (EI) were made on printed anteroposterior pelvis radiographs. Age-specific percentiles were calculated for these measures using published norms. Significant outliers (≤10th/≥90th percentile) were reported where applicable. RESULTS: A total of 168 patients with mean age at diagnosis of 8.0±1.3 years met inclusion criteria (81.5% male). Mean acetabular index for the entire cohort was 16.8±4.1 degrees; 58 hips (34.5%) were significantly dysplastic compared with normative data. Mean lateral center-edge angle was 15.9±5.2 degrees at diagnosis; 110 (65.5%) were ≤10th percentile indicating dysplasia (by this metric). Mean NSA overall was 136.5±7.0 degrees. Fifty-one (30.4%) and 20 (11.9%) hips were significantly varus (≤10th percentile) or valgus (≥90th percentile), respectively. Thirty-five hips (20.8%) were the third articulo-trochanteric quartiles or higher suggesting a higher-riding trochanter at baseline. Mean EI was 15.5%±9.0%, while 63 patients (37.5%) had an EI ≥20%. CONCLUSIONS: The present study finds significant variation in baseline anatomy in children with early-stage LCPD, including a high prevalence of coexisting acetabular dysplasia as well as high/low NSAs. These variations suggest that the "one-surgery-fits-all" approach may lack specificity for a particular patient; a potentially wiser option may be an anatomic-specific containment operation (eg, acetabular-sided osteotomy for coexisting dysplasia, varus femoral osteotomy for valgus NSA). LEVEL OF EVIDENCE: Level IV.

Feasibility of Magnetic Resonance Angiography in Patients With Legg-Calvé-Perthes Disease.

BACKGROUND: The etiology of Legg-Calvé-Perthes disease (LCPD) remains unknown; however, interruption of medial circumflex femoral artery (MCFA) supply to the femoral head is the key pathogenic factor. The main purpose of this study is to determine the feasibility of using magnetic resonance angiography (MRA) to evaluate the course of the MCFA in the normal and affected hips of patients with unilateral LCPD. METHODS: We analyzed 24 patients with unilateral LCPD using a time-resolved imaging of contrast kinetics magnetic resonance angiography (TRICKS-MRA). The course of the MCFA was divided into 4 segments in the coronal plane and in 3 segments in the axial plane, based on its location with respect to the femoral neck. The visibility of each segment was studied in the normal and affected sides. The segments were defined as not visible when no contrast was seen within the vessel lumen or visible when the lumen was partially or completely visualized with contrast. The statistical analysis was done using the χ2 test. RESULTS: TRICKS-MRA provided well-defined images of the first 2 segments of the MCFA on both the normal and affected sides of patients with LCPD (P=1). In half of the patients, the third segment was also visible using TRICKS-MRA on both sides (P=1). The fourth segment of the MCFA, which was the ascending lateral epiphyseal segment, was not visible on either side (P=0.49). No significant difference was found between the normal and affected hips in terms of visibility of the 4 segments of the MCFA using TRICKS-MRA. Anastomosis of the MCFA with the inferior gluteal artery was found in 3 hips (2 hips with LCPD and 1 normal hip). CONCLUSIONS: TRICKS-MRA provides well-defined images of the arterial supply to the proximal femoral epiphysis in children with LCPD, presenting a noninvasive and radiation-free alternative to conventional angiography. However, the TRICKS-MRA method used did not allow visualization of the ascending lateral epiphyseal segment of MCFA in the affected and the contralateral normal side. We believe that further advancement of this noninvasive imaging technique may open new opportunities for research aimed at evaluating the vascular supply of the femoral head in children. LEVEL OF EVIDENCE: Level IV-case-control study.

Team approach: Management of osteonecrosis in children with acute lymphoblastic leukemia.

With current treatments for acute lymphoblastic leukemia (ALL), the overall prognosis for survival is favorable. Increasing emphasis is placed on recognizing and managing the long-term consequences of ALL and its treatment, particularly involving osteonecrosis. Early osteonecrosis diagnosis and management may improve outcomes and is best accomplished through coordinated teams that may include hematologic oncologists, radiologists, orthopedic surgeons, physical therapists, and the patient and their family. Magnetic resonance imaging is the "gold standard" for diagnosis of early-stage and/or multifocal osteonecrosis. Treatments for osteonecrosis in ALL patients are risk stratified and may include observation, corticosteroid or chemotherapy adjustment, and pharmaceutical or surgical approaches.

A Comparison of Transphyseal Neck-Head Tunneling and Multiple Epiphyseal Drilling on Femoral Head Healing Following Ischemic Osteonecrosis: An Experimental Investigation in Immature Pigs.

BACKGROUND: Two operative procedures are currently advocated to stimulate the necrotic femoral head healing in children with Legg-Calve-Perthes disease: transphyseal neck-head tunneling (TNHT) and multiple epiphyseal drilling (MED). The purpose of this study was to compare the bone healing and physeal function after treatment with TNHT or MED in a piglet model of ischemic osteonecrosis. METHODS: Eighteen piglets were induced with osteonecrosis by surgically placing a ligature tightly around the right femoral neck. One week later, the piglets were assigned to 1 of 3 treatment groups (n=6/group): (1) local nonweight bearing only (NWB), (2) TNHT plus NWB, or (3) MED plus NWB. The unoperated left femoral heads were used as normal controls. The animals were euthanized at 8 weeks after osteonecrosis induction. Histologic, histomorphometric, radiographic, microcomputed tomography (CT), and calcein-labeling assessments were performed. Statistical analysis included a 1-way ANOVA. RESULTS: Micro-CT analyses showed higher femoral head bone volume in the MED group compared with the TNHT and the NWB groups (P<0.01). The MED group had a higher mean trabecular number (P<0.001) and new bone formation (P=0.001) based on calcein-labeling parameters compared with the TNHT and the NWB groups. In addition, the osteoclast number per bone surface was lower in the MED group compared with the NWB group (P=0.001). Histologic and micro-CT assessments of the proximal femoral physis revealed a larger physeal disruption at the site of physeal drilling in the TNHT group compared with the MED group. However, no significant differences in physeal elongation (P=0.61) and femoral neck length (P=0.31) were observed between the treatment groups. CONCLUSIONS: MED produced a higher bone volume and stimulated greater bone formation than the TNHT or the NWB alone. Both procedures did not produce a significant physeal growth disturbance during the study period. CLINICAL RELEVANCE: This preclinical study provides evidence that MED produces more favorable bone healing than the TNHT in a large animal model of Legg-Calve-Perthes disease.