A retrospective study describing the acetabular consequences of Legg- Calve-Perthes disease.

PURPOSE: Legg Calve Perthes disease (LCPD) is a paediatric hip disorder caused by ischemia of the femoral epiphysis, causing femoral head deformity when untreated. This study aims to determine if previously validated pelvic obliquity radiographic parameters, used for assessing acetabular retroversion in developmental dysplasia of the hip, are applicable to patients with LCPD and its prognostic value. METHOD: A retrospective study of patients with Legg Calve Perthes disease was carried out, analysing 4 pelvic parameters: Ilioischial Angle, Obturator Index, Sharp's Angle and Acetabular Depth-Width Ratio (ADR). The differences between healthy and affected hips were studied, and subsequently, it was assessed whether these parameters have prognostic value in the disease outcome. RESULTS: Statistically significant differences have been obtained in the ilioischial angle, obturator index and ADR, between the affected and healthy hip. However, only the Acetabular Depth-Width Ratio showed predictive value for the disease outcome. CONCLUSION: Although this study revealed differences in pelvic parameters between healthy and diseased hips, with only the ADR showing statistical significance in the disease's evolution and prognosis, further studies with larger sample sizes are necessary.

Effects of acute femoral head ischemia on the growth plate and metaphysis in a piglet model of Legg-Calvé-Perthes disease.

OBJECTIVE: To determine the effects of acute (≤7 days) femoral head ischemia on the proximal femoral growth plate and metaphysis in a piglet model of Legg-Calvé-Perthes disease (LCPD). We hypothesized that qualitative and quantitative histological assessment would identify effects of ischemia on endochondral ossification. DESIGN: Unilateral femoral head ischemia was surgically induced in piglets, and femurs were collected for histological assessment at 2 (n = 7) or 7 (n = 5) days post-ischemia. Samples were assessed qualitatively, and histomorphometry of the growth plate zones and primary spongiosa was performed. In a subset of samples at 7 days, hypertrophic chondrocytes were quantitatively assessed and immunohistochemistry for TGFß1 and Indian hedgehog was performed. RESULTS: By 2 days post-ischemia, there was significant thinning of the proliferative and hypertrophic zones, by 63 µm (95% CI -103, -22) and -19 µm (95% CI -33, -5), respectively. This thinning persisted at 7 days post-ischemia. Likewise, at 7 days post-ischemia, the primary spongiosa was thinned to absent by an average of 311 µm (95% CI -542, -82) in all ischemic samples. TGFß1 expression was increased in the hypertrophic zone at 7 days post-ischemia. CONCLUSIONS: Alterations to the growth plate zones and metaphysis occurred by 2 days post-ischemia and persisted at 7 days post-ischemia. Our findings suggest that endochondral ossification may be disrupted at an earlier time point than previously reported and that growth disruption may occur in the piglet model as occurs in some children with LCPD.

Avascular necrosis of the femoral head in a cynomolgus macaque (Macaca fascicularis).

A cynomolgus macaque presented with right hindlimb lameness as well as crepitus and decreased passive range of motion of the right coxal joint. Radiography and histopathology were consistent with avascular necrosis of the femoral head. This case is the first published report of this condition in a cynomolgus macaque.

Incidence of total hip arthroplasty in patients with Legg-Calve-Perthes disease after conservative or surgical treatment: a meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to determine the incidence of total hip arthroplasty (THA) in patients with Legg-Calve-Perthes disease (LCPD) treated conservatively or surgically and factors influencing the incidence of THA. METHODS: Long-term follow-up studies on the conservative or surgical treatments of LCPD from 1950 to 2021 were conducted using six public databases. Articles were screened by two investigators (PRISMA guidelines), and the quality of the included publications (n = 27) was assessed (MINORS criteria). R version 4.2.1 was used for statistical analysis. RESULTS: The overall incidences of THA were 6.8% and 5.14% in patients who were treated conservatively and surgically, respectively. At disease onset, the incidences of THA were 6.79% and 6.17% after conservative treatment and surgery in patients aged < seven years, respectively, and 16.97% and 3.61% in patients aged > seven years, respectively. The incidences of THA were 4.91%, 5.19%, and 23.18% in patients who were treated conservatively with ≤ 30, 30-40, and > 40 years of follow-up, respectively, and 3.68%, 3.11%, 9.66%, and 17.92% in patients who were treated surgically with ≤ ten, ten to 20, 20-40, and > 40 years of follow-up, respectively. In patients who received conservative treatment, the incidences of THA were 5.79% and 5.29% in patients with Stulberg I-II and III-V, respectively. In surgically treated patients, the incidence of THA was 0% in Stulberg I-II and 8% in Stulberg III-V. CONCLUSION: Patients with LCPD had relatively low incidences of THA. The greater the age at disease onset and longer the follow-up, the higher the incidence of THA; however, the Stulberg classification was not directly associated with the incidence of THA.

Development of acetabular retroversion in LCPD hips-an observational radiographic study from early stage to healing.

BACKGROUND: Acetabular retroversion is observed frequently in healed Legg-Calvé-Perthes disease (LCPD). Currently, it is unknown at which stage and with what prevalence retroversion occurs because in non-ossified hips, retroversion cannot be measured with standard radiographic parameters. METHODS: In a retrospective, observational study; we examined pelvic radiographs in children with LCPD the time point of occurrence of acetabular retroversion and calculated predictive factors for retroversion. Between 2004 and 2017, we included 55 children with a mean age of 5.7 ± 2.4 years at diagnosis. The mean radiographic follow-up was 7.0 ± 4.4 years. We used two new radiographic parameters which allow assessment of acetabular version in non-ossified hips: the pelvic width index and the ilioischial angle. They are based on the fact that the pelvic morphology differs depending on the acetabular version. These parameters were compared among the four Waldenström stages and to the contralateral side. Logistic regression analysis was performed to determine predictive factors for acetabular retroversion. RESULTS: Both parameters differed significantly among the stages of Waldenström (p < 0.003 und 0.038, respectively). A more retroverted acetabulum was found in stage II and III (prevalence ranging from 54 to 56%) compared to stage I and IV (prevalence ranging from 23 to 39%). In hips of the contralateral side without LCPD, the prevalence of acetabular retroversion was 0% in all stages for both parameters. Predictive factors for retroversion were younger age at stage II and IV, collapse of the lateral pillar in stage II or a non-dysplastic hip. CONCLUSIONS: This is the first study evaluating acetabular version in children with LCPD from early stage to healing. In the developing hip, LCPD may result in acetabular retroversion and is most prevalent in the fragmentation (stage II) and early healing stage (stage III). Partial correction of acetabular retroversion can occur after healing. This has a potential clinical impact on the timing and type of surgical correction, especially in pelvic osteotomies for correction of acetabular version. LEVEL OF EVIDENCE: Level III, retrospective observational study.

The quality of online information on Legg-Calvé-Perthes disease: can we do better?

INTRODUCTION: As patients increasingly utilize the Internet to obtain health-related information, the accuracy and usability of information prove critical, especially for patients and parents seeking care for relatively common orthopedic childhood disorders such as Legg-Calvé-Perthes (LCP) disease. Therefore, the purpose of this study is to evaluate available online health information regarding LCP disease. The study specifically seeks to (1) examine the accessibility, usability, reliability, and readability of online information, (2) compare the quality of sites from different sources, and (3) determine whether Health on the Net Foundation Code (HON-code) certification guarantees higher quality of information. MATERIALS AND METHODS: Websites from a query of both Google and Bing were compiled and scored using the Minervalidation tool (LIDA), an appraisal tool quantifying website quality, along with the Flesch-Kinkaid (FK) analysis, a metric assessing readability of content. All sites were organized based on source category [academic, private physician/physician group, governmental/non-profit organization (NPO), commercial, and unspecified] and HON-code certification. RESULTS: Physician-based and governmental/NPO sites had the highest accessibility, the unspecified site group were the most reliable and usable, and the physician-based group was found to require the least education to comprehend. Unspecified sites had a significantly higher rating of reliability than physician sites (p = 0.0164) and academic sites (p < 0.0001). HON-code-certified sites were found to have greater scores across quality domains along with being easier to read compared to sites without certification, with significantly higher reliability scoring (p < 0.0001). CONCLUSIONS: As a whole, information on the Internet regarding LCP disease is of poor quality. However, our findings also encourage patients to utilize HON-code-certified websites due to their significantly higher reliability. Future studies should analyze methods of improving this publicly available information. Additionally, future analyses should examine methods for patients to better identify reliable websites, as well as the best mediums for optimized patient access and comprehension.

Quantitative T2 and T1ρ mapping are sensitive to ischemic injury to the epiphyseal cartilage in an in vivo piglet model of Legg-Calvé-Perthes disease.

OBJECTIVE: To determine if the quantitative MRI techniques T2 and T1ρ mapping are sensitive to ischemic injury to epiphyseal cartilage in vivo in a piglet model of Legg-Calvé-Perthes disease using a clinical 3T MRI scanner. We hypothesized that T2 and T1ρ relaxation times would be increased in the epiphyseal cartilage of operated vs contralateral-control femoral heads 1 week following onset of ischemia. DESIGN: Unilateral femoral head ischemia was surgically induced in eight piglets. Piglets were imaged 1 week post-operatively in vivo at 3T MRI using a magnetization-prepared 3D fast spin echo sequence for T2 and T1ρ mapping and a 3D gradient echo sequence for cartilage segmentation. Ischemia was confirmed in all piglets using gadolinium contrast-enhanced MRI. Median T2 and T1ρ relaxation times were measured in the epiphyseal cartilage of the ischemic and control femoral heads and compared using paired t-tests. Histological assessment was performed on a subset of five piglets. RESULTS: T2 and T1ρ relaxation times were significantly increased in the epiphyseal cartilage of the operated vs control femoral heads (ΔT2 = 11.9 ± 3.7 ms, 95% CI = [8.8, 15.0] ms, P < 0.0001; ΔT1ρ = 12.8 ± 4.1 ms, 95% CI = [9.4, 16.2] ms, P < 0.0001). Histological assessment identified chondronecrosis in the hypertrophic and deep proliferative zones within ischemic epiphyseal cartilage. CONCLUSIONS: T2 and T1ρ mapping are sensitive to ischemic injury to the epiphyseal cartilage in vivo at clinical 3T MRI. These techniques may be clinically useful to assess injury and repair to the epiphyseal cartilage to better stage the extent of ischemic damage in Legg-Calvé-Perthes disease.

Comparative effectiveness of treatment modalities in severe Legg­Calvé­Perthes disease: Systematic review and network meta­analysis of observational studies.

PURPOSE: There are several treatment modalities for Legg-Calvé-Perthes disease (LCPD), self-limiting, avascular osteonecrosis of the femoral head in children. Most treatments focus on containment of the weakened femoral head, but there is no consensus on the best modality for severe LCPD. Therefore, we compared the effectiveness of all treatment modalities for severe LCPD. MATERIALS AND METHODS: We searched the PubMed, Embase, and Scopus up until July 2021 for studies that investigated LCPD treatment effectiveness. A network meta-analysis was performed to examine the comparative effectiveness in terms of the ability to achieve radiographic spherical congruity of the hip joint after skeletal maturity. The risk ratio (RR) and 95% confidence interval (CI) of each treatment modality were estimated from both direct and indirect evidence. Treatment ranking was based on Surface Under the Cumulative Ranking curve (SUCRA). RESULTS: A total of 857 studies were identified and 34 comparative studies with 3718 affected hips comparing seven different LCPD treatment modalities were included. Compared with symptomatic treatment, combined osteotomy was the most effective modality (RR = 1.47, 95% CI 0.90 to 2.42, SUCRA = 0.8), followed by femoral varus osteotomy (RR = 1.31, 95% CI 1.06 to 1.60, SUCRA = 0.7), and Salter innominate osteotomy (RR = 1.25, 95% CI 0.95 to 1.65, SUCRA = 0.6). CONCLUSIONS: Combined osteotomy is the most effective procedure in terms of improving the spherical congruity of the hip joint in severe LCPD patients. However, the superiority of operative treatments seems to be limited to patients older than eight years old.

Congenital growth hormone deficiency associated with hip dysplasia and Legg-Calve-Perthes disease.

OBJECTIVE: Growth hormone deficiency (GHD) is usually treated with recombinant human GH (rhGH), and this has been rarely associated with hip disorders. We analysed the clinical data of patients with congenital GHD receiving rhGH who had associated hip dysplasia or Legg-Calve-Perthes disease (LCPD), with a view to determining whether the hip dysplasia was associated with the underlying disease or with rhGH treatment. DESIGN: We performed a retrospective analysis of paediatric and adolescent patients seen between 1992-2018 with congenital GHD and hip disorders. Data were collected through a review of the patients' medical records and included demographics, clinical and imaging data, and the time frame between the onset of the symptoms related to the hip disorders and the onset of GH treatment. RESULTS: Of the 13 patients with hip disorders, hip dysplasia was present in ten patients and LCPD in three. Hip dysplasia was diagnosed before rhGH was initiated in 50% of cases. These patients had bilateral hip dysplasia and isolated GHD. LCPD was diagnosed in one patient before rhGH was commenced and did not progress. In two patients, LCPD was diagnosed after rhGH was started and did temporarily progress in one of them, but rhGH was not discontinued because LCPD did not seem to be related to rhGH treatment. CONCLUSIONS: This study suggests that hip dysplasia could be a manifestation of an underlying GHD. Additionally, rhGH treatment may not necessarily be causative of LCPD.

High blood pressure and overweight in children with Legg-Calvé-Perthes disease: a nationwide population-based cohort study.

PURPOSE: Legg-Calvé-Perthes disease (LCPD) and its association with cardiovascular diseases, obesity and hypertension has been consistently observed but remains cloudy. This study aimed to investigate the presence of hypertension and overweight/obesity at diagnosis of LCPD and at a 2-year follow-up and its association with age, sex and lateral pillar classification. METHOD: We compared blood pressure (BP) (n = 93) and body mass index (BMI) (n = 125) in patients registered in the Perthes' register - a part of the Swedish pediatric orthopedic quality register (SPOQ) - with normative data for children with the same age and sex. RESULTS: In children with LCPD 19% had high BP. At the 2-year follow-up, 13% had high BP. For children with LCPD, 30% were either overweight or obese. At the 2-year follow-up, 32% were either overweight or obese. Paired analysis showed stable BMI z-score between these 2 measurements. The sample size of this study was too small to analyze possible associations of high BP or BMI with age, sex and lateral pillar classification. CONCLUSIONS: The prevalence of hypertension was higher in children with LCPD compared to general pediatric normative data. The same pattern was seen for overweight/obesity. Further studies are needed to investigate whether BP and obesity are catalyzing factors in the etiology of LCPD.

Global differences in the treatment of Legg-Calvé-Perthes disease: a comprehensive review.

INTRODUCTION: Global discussions regarding the treatment of Legg-Calvé-Perthes disease (LCPD) are still controversial. The aim of this study was to characterize the worldwide regional differences in nonoperative and operative treatment for LCPD. MATERIALS AND METHODS: Based on a comprehensive literature search, 123 studies describing the results of nonoperative and operative treatment for LCPD were included. Overall, disease and outcome parameters of 6,968 hips were recorded and compared among the continents-Europe, North America, Asia, Africa, South America, and Australia. RESULTS: Our results showed that the continents differed regarding initial disease progression and therapeutic decision-making, but the final outcome was comparable. The reported proportion of affected hips with mild presentation tended to be higher in Europe, North America, and Africa, whereas disease progression was more severe in Asia, Australia, and South America. Nonoperative treatment was reported more frequently in Europe and North America, while operative management was more common in the rest of the world. Femoral osteotomy was performed more frequently than pelvic osteotomy worldwide, but pelvic osteotomy was comparably more common in North America, Australia, and South America. CONCLUSIONS: The continents differed in terms of therapies for LCPD, while the final outcome was similar. Studies with greater evidence and larger sample size are needed to evaluate the effect of therapeutic measures on LCPD outcome. LEVEL OF EVIDENCE: III (systematic review of level III studies).

Association of IL-6 -174G > C and -572G > C Polymorphisms with Risk of Legg-Calve-Perthes Disease in Iranian Children.

BACKGROUND: Legg-Calve-Perthes disease (LCPD) is an idiopathic avascular necrosis of the capital femoral epiphysis of the femoral head with multifactorial etiology. The aim of this study was to analyze the association of IL-6 polymorphisms with LCPD risk in Iranian children. Methods: The study comprised of 45 children diagnosed with LCPD and 60 healthy subjects. The IL-6 -174 G > C and -597 G > C polymorphisms were genotyped by PCR-RFLP assay. Odds ratios (OR) and 95% confidence intervals (CI) were calculated on the risk genotypes and alleles. Results: The mutant homozygote genotype (CC) of IL-6 -174 G > C polymorphism was associated with increased risk of LCPD (OR 3.554; 95% CI: 0.1.578-8.004; p = 0.002). There was no significant association between IL-6 -597 G > C polymorphism and an increased risk of LCPD. Conclusions: Our results suggest that the IL-6 -174 G > C but not the IL-6 -597 G > C polymorphism may increase LCPD susceptibility in Iranian children.

Legg Calvé Perthes disease in the dog.

Legg Calvé Perthes disease (LCPD) is a developmental abnormality that usually affects young small breed dogs. Although the etiology is still uncertain, the pathogenesis is very similar to that described in humans. Diagnosis with physical examination and medical imaging is relatively easy. Treatments offered in dogs, mainly surgical, are also presented. Legg Calvé Perthes disease has many similarities between children and puppies. Dog is therefore an interesting spontaneous model of aseptic osteonecrosis.

Bilateral total hip arthroplasty through minimally invasive direct anterior approach after Legg-Calvé-Perthes disease.

Bilateral secondary osteoarthritis of the hip may affect also young patients following bilateral hip diseases such as slipped capital femoral epiphysis and developmental hip dysplasia. We report the case of an 18- year old male with a previous diagnosis of Legg-Calvé-Perthes disease who underwent a bilateral total hip arthroplasty through minimally invasive direct anterior approach, with optimal results at 1-year follow up.

IL6 receptor blockade preserves articular cartilage and increases bone volume following ischemic osteonecrosis in immature mice.

OBJECTIVE: Juvenile ischemic osteonecrosis (JIO) of the femoral head is one of the most serious hip disorders causing a permanent deformity of the femoral head in childhood. We recently reported that interleukin 6 (IL6) is predominantly increased in the hip synovial fluid of patients with JIO and that articular chondrocytes are primary source of IL6. This study investigated whether an inhibition of IL6 receptor improves cartilage preservation and bone healing in JIO. METHOD: A small animal model (i.e., 6-week-old mouse) of JIO was treated with either saline or tocilizumab, an IL6 receptor blocker, for 6 weeks. RESULTS: TUNEL-positive chondrocytes in the articular cartilage were reduced by the tocilizumab treatment, concomitant with the increase in cartilage matrix. The levels of a cartilage anabolic marker Sox9 was significantly increased in the articular cartilage of mice treated with tocilizumab. Micro-CT assessment showed tocilizumab treatment significantly increased trabecular epiphyseal bone volume (P = 0.001, n = 10), thickness (P = 0.007) and number (P = 0.014) and decreased bone separation (P = 0.002) and its deformity (P = 0.003). A bone formation marker, BMP2, and an angiogenic marker, vascular endothelial growth factor (VEGF), were both significantly increased by tocilizumab treatment under hypoxia using human chondrocytes while the bone resorption marker, RANKL/OPG ratio, was reduced. CONCLUSION: Tocilizumab treatment following ischemic osteonecrosis has cartilage anabolic effect and increases bone volume in JIO mouse model. The findings lead to a possible application of tocilizumab for preclinical study using a large animal model of JIO and a clinical trial to validate this treatment.

[Hip arthroplasty after pelvic and femoral osteotomies]. / Hüftendoprothetik nach Osteotomien des Beckens und des proximalen Femurs.

Pelvic and femoral osteotomies can be a challenge even for experienced orthopedic surgeons. Residual metal may complicate the insertion of the endoprosthesis in some cases. Sometimes, the anatomical modification of the previous osteotomy complicates the total hip replacement. This may require the use of an acetabular revision system for the primary implantation. Femoral deformities can require additional osteotomies of the femur during the implantation. In every case, accurate preoperative planning should be performed. A preoperative CT with 3D reconstruction is a powerful tool for further information beyond conventional imaging.

[Perthes disease-diagnosis, classification and treatment based on Aachen-Dortmund treatment algorithm]. / M. Perthes ­ Diagnostik, Klassifikation und Therapie anhand des Aachen-Dortmunder Therapiealgorithmus.

Legg-Calvé-Perthes disease is a multifactorial idiopathic necrosis of the hip that typically occurs in childhood between the ages of 3 and 12. Treatment adapted to the stadium of the disease and to the clinical findings is medical art. The treatment is focused on the preservation or recovery of the arthrogenic containment of the femoral head. Multiple treatment options are available. The indications for treatment can be derived from clinical and radiological pathology. Structuring of the therapy options is the aim of this publication. For this purpose, a clear and concise overview of relevant clinical findings and useful radiographic classifications as well as reasonable therapy is presented.

Monobloc implants in cementless total hip arthroplasty in patients with Legg-Calve-Perthes disease: a long-term follow-up.

BACKGROUND: The purpose of this study was to evaluate 10-year outcomes in cementless monobloc total hip arthroplasty (THA) in a group of hips with Legg-Calve-Perthes disease (LCPD). METHODS: We reviewed 71 patients (88 hips) who underwent cementless THA with a diagnosis of LCPD from 2003 to 2009. From the total of 71 patients, 34 men and 37 women with an average age of 49.94 years were included. The mean follow-up period was 10 years. RESULTS: The mean Harris Hip Score improved significantly from 46.42 to 89.70. Similarly, the postoperative range of motion, hip dysfunction and osteoarthritis outcome score and SF-12 score also significantly improved. The mean leg lengthening was 22.1 mm. During the follow-up, eight complications were noted, including two cases of intraoperative femoral fractures, two cases of sciatic nerve paralysis, two cases of heterotrophic ossifications, one case of thigh pain and one case of dislocation. One revision was conducted for a periprosthetic fracture, and the survivorship at 10 years was 98.3%. CONCLUSIONS: These data suggest that the monobloc stem can lead to satisfactory outcomes for clinical function, radiological evaluation, restoration of the normal limb lengths, complications, and survivorship among LCPD patients undergoing total hip arthroplasty.

Legg-Calvé-Perthes disease: classifications and prognostic factors.

INTRODUCTION: Legg-Calvé-Perthes Disease (LCPD) represents idiopathic avascular necrosis of femoral head in pediatric population. Indications for treatment depend mostly on prognosis about femoral head sphericity and hip congruence at the end of growth. The aim of this review is to highline prognostic factors of LCPD. METHODS: Bibliographic search in PubMed allowed selection of 33 articles concerning prognostic factors and/or classification of LCPD. CONCLUSION: Clinical factors of poor prognosis are overweight, female sex, age exceeding 6 years old, and lack of hip abduction. Radiologically, Herring's classification is consensual because of its high prognostic value and very good reproducibility. The other signs of femoral head "at-risk" and the assessment of the reduction in abduction of the femoral head in the acetabulum are also prognostic of late evolution. MRI seems to be a future tool in assessing the fate of hips in LCPD. It is likely that a better understanding of LCPD etiology would precise the prognosis of this disease.