Classifications in Brief: Japanese Investigation Committee Classification for Idiopathic Osteonecrosis of the Femoral Head.

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.

Aseptic osteonecrosis of the femoral head (ONFH) is a debilitating orthopedic disorder that predominantly affects young adults and has a multifactorial etiology. In mining-intensive regions such as Katanga (Democratic Republic of the Congo), chronic exposure to trace metal elements (TMEs) has raised concerns about potential environmental contributors to bone disease. This study aimed to investigate the association between bone TME accumulation and the occurrence of idiopathic ONFH in an environmentally exposed population. A case-control study was conducted between 2017 and 2025 at Medpark Clinic, Lubumbashi. Femoral head specimens were collected from 56 patients undergoing total hip arthroplasty, including 36 cases of idiopathic ONFH and 20 controls with primary osteoarthritis. Bone concentrations of eleven TMEs (Pb, Co, Cd, Cr, Zn, Cu, As, Mn, Mg, Ni, Al) were quantified using inductively coupled plasma-optical emission spectrometry (ICP-OES). Exposure was defined as a Z-score > 2 compared with a local reference population. Bivariate and multivariate logistic regression analyses were performed to assess associations. Patients with ONFH were significantly younger than controls (mean age: 49.5 vs. 62.9 years; p = 0.004). Bone concentrations of lead and cobalt were markedly higher in ONFH cases. In multivariate analysis, elevated bone lead levels (adjusted OR = 23.75; 95% CI: 2.30-181.57) and age ≤ 50 years were independently associated with ONFH. No significant associations were found for other TMEs. This study provides the first direct evidence that chronic bone accumulation of lead and cobalt is strongly associated with idiopathic ONFH in a mining-exposed African population. These findings highlight the urgent need for environmental monitoring, targeted public health interventions, and early clinical surveillance in high-risk regions.

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.

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

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

An epidemiologic study compared 112 patients with idiopathic osteonecrosis (ON) of the femoral head having no history of systemic corticosteroid use and 168 hospital controls. Patients and controls were matched for gender, age, ethnicity, hospital, and time of initial diagnosis. The role of alcohol intake, cigarette smoking, and occupational status was assessed in relation to the development of ON. The relative risk (RR), the measure of association between ON and the risk factors, was statistically adjusted for the potential confounding effects of other factors by the conditional logistic regression model. An elevated risk for regular drinkers (RR = 7.8, p less than 0.001) and a clear dose-response relationship was noted (test for trend; p less than 0.001): the RRs were 3.3, 9.8, and 17.9 for current consumers of less than 400, 400-1000, and greater than or equal to 1000 ml/week of alcohol, respectively. A significantly increased risk was found for current smokers (RR = 3.9; p less than 0.05). However, the cumulative effect of smoking was not evident. No increased risk was found for obesity or for heavy physical work. Regarding causation of ON, this study confirmed the consistent association with excessive alcohol intake and suggested the immediate untoward effects of smoking. The role of heavy physical work as a form of mechanical stress was not correlated with ON.

Idiopathic osteonecrosis (IO) of the femoral head in adults is a serious disease that leads to permanent disability at the most working age (in the 3-5th decade of life). Its essence lies in subchondral necrosis of the bone matter of the head in the upper, most loaded segment, followed by impaction of the head and the development of the most severe deforming arthrosis. The disease develops spontaneously, for no apparent reason, and should be distinguished from post-traumatic head necrosis after neck fractures and hip dislocations.

Comparative analysis of serum proteomes: discovery of proteins associated with 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.].

Idiopathic osteonecrosis of the femoral head (INFH) seriously affects patients’ activities and is a heavy burden to society and patients’ families. Therefore, the early diagnosis and treatment of INFH is essential in reducing pain and burden. In the present study, the cancellous bone under the cartilage of the femoral head was isolated from patients with INFH and femoral neck fracture (FNF). Histological examination revealed that the bone trabecular and the medullary cavity in the INFH group compared with those in the FNF group. Whole-transcriptome sequencing (WTS), a recently applied technology, plays a significant role in the screening of risk factors associated with the onset of femoral head necrosis. Herein, WTS was used to obtain the mRNA expression profile in the cancellous bone of the femoral head isolated from 5 patients with INFH and 5 patients with FNF. Compared with the FNF group, a total of 155 differentially expressed genes were identified in the INFH group. Among these genes, 96 and 59 were upregulated and downregulated, respectively. Reverse transcription-quantitative PCR and western blot analyses revealed that leucine-rich repeat-containing 17 (LRRC17) displayed the most significantly decreased mRNA and protein expression levels between the INFH and FNF groups. The expression profile of the differentially expressed genes and LRRC17 protein in the INFH and FNF groups was consistent with that obtained by WTS. LRRC17, a leucine repeat sequence, plays a significant role in regulating bone metabolism, thus indicating that LRRC17 downregulation could affect bone metabolism and could be considered a key factor in the pathogenesis of INFH.

PurposeNitric oxide (NO) synthesised by endothelial NO synthase (eNOS) is a potent regulator of internal haemodynamics. A polymorphism in intron 4 of the eNOS is associated with different vascular disorders. We investigated the potential involvement of this polymorphism in idiopathic and secondary osteonecrosis of the femoral head (ONFH) in Polish patients.MethodsWe performed a study involving 68 patients with ONFH (45 idiopathic and 23 secondary) and 100 healthy controls. All subjects were genotyped for the eNOS4 polymorphism by the polymerase chain reaction followed by agarose gel electrophoresis.ResultsThe analysis revealed that the frequencies of eNOS4 genotypes were significantly different in ONFH patients (both idiopathic and secondary) than in controls. The frequencies of the 4a allele were significantly higher in the total group of patients versus controls [22.79 vs 9 %, p = 0.00039, odds ratio (OR) 2.98]. In subgroup analysis the 4a allele increased significantly in both idiopathic (20 vs 9 %, p = 0.0074, OR = 2.52) and secondary (28.26 vs 9 %, p = 0.00047, OR = 3.98) ONFH patients compared to control subjects. The frequency of the 4a/b genotype in the total group of patients (36.76 vs 16 %, p = 0.0011, OR = 3.24) as well as patients with idiopathic (35.56 vs 16 %, p = 0.0069, OR = 2.96) and secondary (39.13 vs 16 %, p = 0.0073, OR = 3.89) ONFH was higher than in the control group.ConclusionsThere was a significantly higher frequency of eNOS 4a allele carriers among the total group of patients as well as in idiopathic and secondary ONFH. This suggests that the eNOS gene polymorphism may be associated with increased risk of ONFH.

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.

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.

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.

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.