Legg-Calvé-Perthes Disease.

Rehabilitation Program After Mesenchymal Stromal Cell Transplantation Augmented by Vascularized Bone Grafts for Idiopathic Osteonecrosis of the Femoral Head: A Preliminary Study

BACKGROUND: Aseptic necrosis of the femoral head in school-age children is a severe, rapidly progressive degenerative and dystrophic disease. A significant proportion of girls aged 10 years with osteonecrosis of the femoral head have been professionally engaged in rhythmic gymnastics. The relationship between professional sports, in particular rhythmic gymnastics, and the development of this pathology and the mechanism of impaired blood flow in the femoral head in such cases remains unclear. The severity of the course and serious consequences of this disease in the form of multidimensional deformities of the femoral head, early arthrosis of the hip joint, and persistent disability, require close attention. AIM: To analyze modern world literature data on the etiology, pathomechanics, and features of the course and treatment of idiopathic aseptic necrosis of the femoral head in children professionally engaged in rhythmic gymnastics. MATERIALS AND METHODS: A literature search on the problem of idiopathic aseptic necrosis of the femoral head in children professionally engaged in rhythmic gymnastics in the open information databases was conducted in PubMed, Science Direct, and Library with an analysis depth of 20 years. RESULTS: The analysis of publications on the osteonecrosis of the femoral head allowed us to talk about the etiological connection of this condition with professional rhythmic gymnastics, namely, high-intensity repetitive loads on the hip joint of a child. Studies using in vivo laser Doppler flowmetry and 3D computer modeling prove the occlusion of blood vessel branches encircling the femur under excessive mechanical stress on the femoral head and potentially unfavorable positions in the hip joint – overextension (hyperextension), external rotation, and abduction. CONCLUSIONS: Professional gymnastics can be a risk factor for the development of osteonecrosis of the femoral head. Frequent late disease diagnoses with the development of severe deformity of the femoral head and end-stage coxarthrosis requiring total hip replacement in adolescents determine the need for early identification of the causes of hip pain in children engaged in gymnastics. The findings will help improve treatment results and reduce the number of organ replacement interventions.

Idiopathic osteonecrosis of the femoral head (ION) is a painful disease of the hip, the pathogenic mechanism of which is still unclear. The most common extraneous factor is steroid treatment. Steroids have inhibiting effects on bone formation and resorption. When bone regenerative treatments are indicated for ION patients who are exposed to steroids, we cannot ignore the effects of corticosteroid itself on bone healing. The aim of this study was to investigate the effects of glucocorticoid on bone regeneration after osteonecrosis of the femoral head in a rat model. Osteonecrosis was induced surgically on the left femoral heads of aged female rats (about 6 months old) on day 0. Methylprednisolone sodium succinate (MPSS) or normal saline was administrated at a dose of 100 mg/kg/day from day 7 to 11. Femoral heads were analyzed histologically. There were no pathological findings in the right femoral heads of the MPSS-treated and saline-treated rats, as control for the contralateral injury. The newly formed bone volume and the osteoclast number were significantly smaller in the MPSS-treated group. The normal bone marrow was regenerated in the saline-treated group, whereas most of the bone marrow space still contained fibroblast-like spindle-shaped cells in the MPSS-treated group on day 42. Alkaline phosphatase-positive cells were only seen in the areas around the regenerated bone marrow cavities. Thus, MPSS inhibits bone formation by suppressing osteoblast proliferation and resorption by suppressing the recruitment of osteoclast precursors. These findings may be useful when designing treatments for ION patients exposed to steroids.

There have been few studies investigating the cumulative effect of individual factors related to bone metabolism on the systemic balance between bone formation and resorption in patients with osteonecrosis of the femoral head (ONFH). We investigated bone mineral density (BMD) of lumbar spine and bone turnover markers that reflect systemic bone metabolism. Two-hundred twenty patients with ONFH were matched to 220 healthy subjects according to age, gender, and body mass index. ONFH patients were divided into steroid-induced (18%), alcoholic (21%), and idiopathic ONFH (61%) and subgroup analysis was performed to exclude the effect of steroid and malnutrition on bone metabolism. We compared lumbar spine bone mineral density (BMD) between groups and measured serum bone-specific alkaline phosphatase (BALP) and urinary deoxypyridinoline/creatinine (Dpd/Cr) ratio. Logistic regression analysis revealed low spine BMD was significantly associated with each subgroup of ONFH when compared with that of the control group (odds ratio of 2.27, 4.24, and 1.86 in alcoholic, steroid, and idiopathic ONFH, respectively). The mean value of serum BALP (27.02U/L) was within the normal reference range while average urine Dpd/Cr ratio (6.24nM/mM) increased in ONFH group when compared with respective reference range. Spine BMD decreased and urinary Dpd/Cr ratio increased in patients with non-traumatic ONFH. Further studies will be necessary to identify whether non-traumatic ONFH is merely a regional disease confined to the femoral head or may affect systemic bone metabolism.

ObjectiveIt is unclear whether idiopathic osteonecrosis of the femoral head (ONFH) is associated with borderline developmental dysplasia of the hip (BDDH). This study aimed to compare the incidence of BDDH between patients with idiopathic ONFH and matched control subjects and determine the influence of BDDH on poor prognosis after core decompression (CD).MethodsWe retrospectively examined 78 consecutive patients (111 hips) with idiopathic ONFH undergoing CD and 1:2 matched with 156 control subjects (222 hips). The anteroposterior pelvic radiographs were used to measure the acetabular anatomical parameters and divide included subjects into BDDH or non‐BDDH group. The incidence of BDDH and acetabular anatomical parameters were compared between patients with idiopathic ONFH and matched controls. Clinical outcomes, such as Harris Hip Score (HHS), progression of collapse, and conversion to total hip arthroplasty (THA), were compared between patients with BDDH and without BDDH in the idiopathic ONFH group, with a mean follow‐up of 72.1 ± 36.6 months.ResultsPatients with idiopathic ONFH had a significantly higher incidence of BDDH than matched controls (29.7% vs 12.2%, p < 0.001). Less acetabular coverage was also found in patients with idiopathic ONFH than in matched controls as demonstrated by lower CEA (28.5° ± 4.7° vs 33.1° ± 5.7°, p < 0.001), AHI (82.4 ± 5.0 vs 86.3 ± 5.4, p < 0.001), ADR (299.6 ± 28.4 vs 318.8 ± 31.3, p < 0.001), and a higher sharp angle (40.0° ± 3.4° vs 37.4° ± 3.7°, p < 0.001). In patients with idiopathic ONFH, the BDDH group had a significantly lower mean HHS at the last follow‐up (83.5 ± 17.4 vs 91.6 ± 9.7, p = 0.015) with a different score distribution (p = 0.004), and a lower 5‐year survival rate with both clinical failure (66.7%, 95% CI 52.4%–84.9% vs 83.7%, 95% CI 75.2%–93.1%; p = 0.028) and conversion to THA (74.6%, 95% CI 60.7%–91.6% vs 92.1%, 95% CI 85.6%–99.0%; p = 0.008) as the endpoints than the non‐BDDH group.ConclusionThe incidence of BDDH was significantly higher in patients with idiopathic ONFH than matched controls, and idiopathic ONFH patients who underwent CD with BDDH had lower mean HHS as well as 5‐year survival rate than those without BDDH. Therefore, BDDH should be considered a risk factor predicting the development of idiopathic ONFH as well as poor prognosis after CD.

AimsTo investigate whether idiopathic osteonecrosis of the femoral head (ONFH) is related to impaired osteoblast activities.MethodsWe cultured osteoblasts isolated from trabecular bone explants taken from the femoral head and the intertrochanteric region of patients with idiopathic ONFH, or from the intertrochanteric region of patients with osteoarthritis (OA), and compared their viability, mineralization capacity, and secretion of paracrine factors.ResultsOsteoblasts from the intertrochanteric region of patients with ONFH showed lower alkaline phosphatase (ALP) activity and mineralization capacity than osteoblasts from the same skeletal site in age-matched patients with OA, as well as lower messenger RNA (mRNA) levels of genes encoding osteocalcin and bone sialoprotein and higher osteopontin expression. In addition, osteoblasts from patients with ONFH secreted lower osteoprotegerin (OPG) levels than those from patients with OA, resulting in a higher receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) ligand (RANKL)-to-OPG ratio. In patients with ONFH, osteoblasts from the femoral head showed reduced viability and mineralized nodule formation compared with osteoblasts from the intertrochanteric region. Notably, the secretion of the pro-resorptive factors interleukin-6 and prostaglandin E2 as well as the RANKL-to-OPG ratio were markedly higher in osteoblast cultures from the femoral head than in those from the intertrochanteric region.ConclusionIdiopathic ONFH is associated with a reduced mineralization capacity of osteoblasts and increased secretion of pro-resorptive factors.Cite this article: Bone Joint Res 2021;10(9):619–628.

This study aimed to investigate whether idiopathic osteonecrosis of the femoral head (ONFH) is associated with alterations in the microstructure, histological characteristics, and transcriptomic signature in the trabecular region of the femoral head. For this purpose, we obtained trabecular bone explants from the femoral head and the intertrochanteric region of patients with idiopathic ONFH and age- matched patients with primary osteoarthritis (OA). Trabecular bone from the femoral head of ONFH patients showed lower trabecular thickness, bone volume fraction and degree of anisotropy, and a higher percentage of empty lacunae than bone samples from the intertrochanteric region of the same patients and from the femoral head of the OA group. The transcriptome analysis identified a substantial number of genes exclusively regulated in the femoral head of ONFH patients. Among these genes, we found that those highly expressed around the necrotic lesion were involved in cell division and immune response. By contrast, downregulated genes were mainly involved in cell adhesion, angiogenesis and bone formation, such as those encoding collagen type I, bone sialoprotein and several bone morphogenetic proteins. These data add new insights into mechanisms involved in the pathophysiology of idiopathic ONFH.

Osteonecrosis of the femoral head (ONFH) is a multifactorial disease and is associated with genetic predisposition, and exposure to certain risk factors. In particular, idiopathic ONFH in twins and the clustering of cases in families have indicated that genetic factors are involved. However, the majority of cases of ONFH are sporadic and various studies have demonstrated that differences in the study design and/or the ethnic groups analyzed leads to different results. The present study performed one of the first genome-wide association studies to identify genetic loci that may increase the risk of idiopathic ONFH. In total, 217 patients with idiopathic ONFH and 217 control samples, without ONFH, were genotyped using Axiom™ chips. Following quality control, 509,886 single-nucleotide polymorphisms (SNPs) were included in the association analysis to identify genetic variants that may influence susceptibility to idiopathic ONFH. The lowest P-value identified by the current study was for an association with rs220324 (P=3.57×10-7), an SNP that is located near to the uromodulin-like 1 gene region on chromosome 21q22.3, although none of the SNPs reached the traditional genome-wide significance level of 5×10–8. However, the DnaJ heat shock protein family (Hsp40) member C6 (DNAJC6) locus, a region between 65.37 and 65.67 Mb located on chromosome 1p31.3, harbored a cluster of SNPs that were associated with idiopathic ONFH at a significance level of P<1×10–5. Four variants, rs10493374, rs12032616, rs17127529 and rs6679032, with marginal associations were located in and around the DNAJC6 locus and were in strong linkage disequilibrium with each other. In conclusion, the current study did not identify any SNPs that were associated with idiopathic ONFH at a genome-wide significance level, however, the results suggest that future studies should investigate the effects of SNPs in the DNAJC6 gene on the idiopathic ONFH risk.

The purpose of this article is to relate intramedullary perfusion of the proximal femur to severity of osteonecrosis of the femoral head by using dynamic contrast-enhanced MRI (DCE-MRI). Twelve patients (14 symptomatic hips) who underwent DCE-MRI and had subsequent core decompression of the femoral head were examined. Hips were graded for severity according to MRI findings and were assigned scores of 0 (negative findings), 1 (focal marrow abnormalities), and 2 (subchondral collapse). Thirteen asymptomatic hips acted as controls. The DCE-MRI data were analyzed by use of a pharmacokinetic two-compartment model. Compared with control hips, there was significantly greater peak enhancement in the femoral head in hips of all grades (p < 0.001) and in the femoral neck (p = 0.001) and intertrochanteric area (p = 0.001) in grade 2 hips. The time to peak was significantly delayed in the femoral head in grade 0 hips (p = 0.02) and in the intertrochanteric area in grade 2 hips (p = 0.003) compared with the controls. As evaluated by DCE-MRI, intramedullary peak enhancement in the femoral head increased with progression of idiopathic osteonecrosis of the femoral head, whereas there was delayed peak enhancement in the femoral head in hips with negative findings and intertrochanteric stasis in advanced osteonecrosis of the femoral head. Such perfusion changes as shown on MRI can occur with early osteonecrosis in the absence of other MRI abnormalities.

Association study of hypoxia inducible factor 1α ( HIF1α) with osteonecrosis of femoral head in a Korean population

Legg-Calvé-Perthes disease consists of idiopathic osteonecrosis of the femoral head, causing proximal femoral growth deformity. Recent advances in surgical technique have permitted safe surgical dislocation of the hip, allowing for correction of femoracetabular impingement. The purpose of this study was to characterize the location and number of lateral epiphyseal arteries supplying the femoral head in children with healed Legg-Calvé-Perthes disease. This retrospective study included nineteen children (twenty-two hips) with a diagnosis of Legg-Calvé-Perthes disease (the LCPD group) and a matched control group of seventeen children (twenty hips) with developmental hip dysplasia. All patients underwent high-resolution contrast-enhanced magnetic resonance imaging (MRI) to visualize the path of the medial femoral circumflex artery and the lateral epiphyseal artery branches supplying the femoral head. All patients in the LCPD group were classified as having Waldenström grade-4 disease. Their average age at the time of MRI was fifteen years (range, eleven to eighteen years). The lateral epiphyseal arteries reliably inserted on the posterior-superior aspect of the femoral neck from a superior-anterior to a superior-posterior position in both groups. An average of 2.63 (standard deviation [SD], 1.47) retinacular vessels were visualized in the LCPD group, compared with 5.20 (SD, 1.06) retinacular vessels in the dysplasia group (p &lt; 0.0001). The lateral epiphyseal arteries of the femoral head reliably insert in a narrow anatomic window on the femoral neck. Reperfusion of the medial femoral circumflex artery does occur in patients with Legg-Calvé-Perthes disease; however, the overall number of vessels is decreased as compared with that in patients with developmental hip dysplasia.

Association of Neutrophil Extracellular Traps with the Development of Idiopathic Osteonecrosis of the Femoral Head

Idiopathic osteonecrosis of the femoral head (ONFH) can be correctly diagnosed in accordance with the established criteria. However, some general orthopedic physicians have misdiagnosed patients as having ONFH. The goal of this study was to clarify the radiologic and clinical features of misdiagnosed patients. This study included 50 patients who were referred to the authors' hospital by general physicians with a diagnosis of ONFH. The correct diagnosis was made based on the Japanese Investigation Committee diagnostic criteria for ONFH. Demographic data were compared between patients with and without ONFH. Of the 50 patients, 24 were diagnosed with other diseases: 10 with osteoarthritis, 7 with transient osteoporosis of the femoral head, 4 with rapidly destructive coxopathy, and 3 with subchondral insufficiency fracture. Seventeen patients who did not have ONFH had magnetic resonance imaging findings that showed a bone marrow edema pattern at the femoral head. The mean age of 62.9 years among patients without ONFH was significantly higher than that of 45.2 years among patients with ONFH. There were 18 female patients in the non-ONFH group and 5 female patients in the ONFH group. Bilateral disease was found in 1 patient in the non-ONFH group and 17 patients in the ONFH group. No patients in the non-ONFH group had a history of systemic steroid administration compared with 11 patients in the ONFH group. Clinical features associated with the non-ONFH group were female sex, older age, unilateral disease, and no history of systemic steroid administration. For patients with these features, the diagnosis of ONFH should be made carefully. [Orthopedics. 2017; 40(1):e117-e123.].

The 2001 revised criteria for diagnosis, classification, and staging of idiopathic osteonecrosis of the femoral head

BackgroundNontraumatic osteonecrosis of the femoral head (ONFH) can be corticosteroid-induced, alcohol-induced, and idiopathic ONFH (IONFH). Although corticosteroid- and alcohol-induced ONFH has been investigated extensively regarding its relationship with blood lipids and coagulation factor levels. However, the effect of blood lipid metabolism and coagulation function on IONFH has rarely been studied. Therefore, this study aimed to analyse the relationship of IONFH with blood lipid and coagulation indicators.MethodsTotal 680 patients diagnosed with IONFH in our institution during January 2011–June 2019 who met the inclusion criteria composed the case group; 613 healthy persons who underwent physical examination at our institution during the same period composed the control group. Propensity scores were used for baseline feature matching, and two matching groups each with 450 patients were established. After the matching, blood lipid and coagulation factor levels of both groups were comparatively analysed.ResultsThe case group showed significantly higher total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) levels, low-density/high-density lipoprotein (LDL/HDL) ratio, and apolipoprotein B (Apo-B) levels than the control group (p < 0.05). Conversely, the HDL and apolipoprotein A (Apo-AI) levels in the case group were significantly lower than those in the control group (p < 0.05). Regarding coagulation indicators, the activated partial thromboplastin time and prothrombin time were lower in the case group than in the control group; however, the differences were insignificant (p > 0.05). Furthermore, fibrinogen (FIB) levels and thrombin time (TT) in the case group were higher than those in the control group. There were significant differences between the two groups only in terms of FIB levels (p < 0.05), while TT was not significantly different (p > 0.05).ConclusionsIONFH has strong associations with blood lipid metabolism and coagulation function, which provide an avenue for exploring the mechanism of IONFH.