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Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_15 | Pages 36 - 36
1 Mar 2013
Cho YJ Lee J Kwak S Chun YS Rhyu KH Won YY Yoo M
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Purpose. There are some concerns about doing hip resurfacing arthroplasty in ONFH due to bone defect which can cause mechanical weakness of femoral component and highly active young age of patients which can cause high wear rate and failure rate. The purpose of this study is to verify the HRA is safe procedure in ONFH in the aspect of mechanical and biological issue. Materials and Methods. Between December 1998 and May 2005, 185 hips of 169 patients underwent MoM HRA using Birmingham Hip Resurfacing System® at single center. 166 hips (26 hips of female, 140 hips of male) of 144 patients have been reviewed for at least 7 years after MoM HRA. Mean follow-up period was 101.8 (84–178) months. Their mean age at the time of operation was 37.7(16–67) years old. Clinically, Harris hip scores (HHS), UCLA activity scores and range of motion were evaluated. Radiologically, the extent of necrotic area in preoperative MRI and radiolucency around implants, narrowing of retained neck, impingement, stress shielding, and heterotopic ossification were evaluated in the serial anteroposterior and groin lateral radiographs of hip. Complications were defined as joint dislocation, infection, implant loosening, femoral neck fracture and pseudotumor. Failure was defined as revision arthroplasty due to the complications. Results. The extent of necrotic area in preoperative MRI was average 37.6 (13.3–65)%. Clinically, average HHS was improved from 81.7 points to 98.5 points at last follow-up. Average UCLA activity score at last follow-up was 9.0 points. Range of motion at last follow-up was very satisfactory. There was no patient with severe pain around hip joint. Radiologically, radiolucency was shown around acetabular component in 2 cases (1.2%) and around stem of femoral components in 3 cases (1.8%). Fracture of femoral neck was seen in 1 case(0.6%). Moderate narrowing changes of retained femoral neck were noticed in 4 cases (2.4%). Impingement was seen in 12 cases (7.2%). We found only 1 case of osteolysis at Gruen zone III of acetabulum. Heterotopic ossification was found in 5 cases (3.0%). There was no case with hip dislocation, infection or pseudotumor. Revision surgeries after the primary resurfacing arthroplasty were performed in 4 cases (2.4%). Three hips were revised to the conventional total hip arthroplasty (THA) because of loosening of acetabular component and femur neck fracture. One case of femoral component loosening was revised to THA using big metal head with retained acetabular component. Conclusions. MoM HRA in ONFH demonstrates good survivorship in average 101.8 months follow-up study. Most of patients show excellent clinical results with high level of activity postoperatively. Prevalence of complications is extremely lower than concern including the allergic reaction to the metal ion. There was no mechanical failure related to bone defect due to ONFH. This results suggests that MoM HRA in ONFH less than 50% of extent of necrosis can be justified


The Bone & Joint Journal
Vol. 107-B, Issue 3 | Pages 308 - 313
1 Mar 2025
Tang H Ling DI Hsu S Chuang C Hsu K Ku LE

Aims. Core decompression is a commonly performed procedure to treat osteonecrosis of the femoral head (ONFH) prior to femoral head collapse. The aim of the study was to identify the incidence of hip arthroplasty after core decompression and the potential risk factors for conversion through a nationwide population-based study. Methods. Patients who received core decompression for ONFH between 1 January 2009 and 31 December 2018 and were followed up until 31 December 2019 (mean 33 months (0.2 to 132)) were retrieved from Taiwan’s National Health Insurance claims database. A total of 2,918 patients were identified and included in the study. The mean age at the time of core decompression was 46 years (SD 12.5), with a male-to-female ratio of 7:3. The first total hip arthroplasty or hip hemiarthroplasty after the index core decompression was considered as the outcome of conversion to hip arthroplasty. For the analysis of conversion risk, patients’ demographic characteristics, economic status, comorbidities, and data on the type of hospital and surgeons’ experience were included. Results. Overall, 20.05% of patients received a hip arthroplasty within six months following core decompression, with the incidence rising to 60.6% by five years and 66.4% by ten years. Multivariable analysis revealed that patients aged over 40 years (HR 1.18 (95% CI 1.07 to 1.30); p = 0.002), who had a history of alcohol abuse (HR 1.57 (95% CI 1.22 to 2.02); p < 0.001), and had their procedures performed at district-level hospitals (HR 1.13 (95% CI 1.00 to 1.26; p = 0.044), were at increased risk of conversion to hip arthroplasty following core decompression. Conclusion. The five- and ten-year cumulative incidence of conversion to hip arthroplasty after core decompression was 60.6% and 66.4%, respectively. Significant risk factors for conversion to hip arthroplasty included age over 40 years, history of alcohol abuse, and procedures performed at district hospitals. Cite this article: Bone Joint J 2025;107-B(3):308–313


Bone & Joint Research
Vol. 13, Issue 11 | Pages 673 - 681
22 Nov 2024
Yue C Xue Z Cheng Y Sun C Liu Y Xu B Guo J

Aims. Pain is the most frequent complaint associated with osteonecrosis of the femoral head (ONFH), but the factors contributing to such pain are poorly understood. This study explored diverse demographic, clinical, radiological, psychological, and neurophysiological factors for their potential contribution to pain in patients with ONFH. Methods. This cross-sectional study was carried out according to the “STrengthening the Reporting of OBservational studies in Epidemiology” statement. Data on 19 variables were collected at a single timepoint from 250 patients with ONFH who were treated at our medical centre between July and December 2023 using validated instruments or, in the case of hip pain, a numerical rating scale. Factors associated with pain severity were identified using hierarchical multifactor linear regression. Results. Regression identified the following characteristics as independently associated with higher pain score, after adjustment for potential confounders: Association Research Circulation Osseous classification stage IIIa or IIIb, bone marrow oedema, grade 3 joint effusion, as well as higher scores on pain catastrophizing, anxiety, and central sensitization. The final model explained 69.7% of observed variance in pain scores, of which clinical and radiological factors explained 37%, while psychological and neurophysiological factors explained 24% and demographic factors explained 8.7%. Conclusion. Multidimensional characteristics jointly contribute to the severity of pain associated with ONFH. These findings highlight the need to comprehensively identify potential contributors to pain, and to personalize management and treatment accordingly. Cite this article: Bone Joint Res 2024;13(11):673–681


Bone & Joint Open
Vol. 5, Issue 5 | Pages 394 - 400
15 May 2024
Nishi M Atsumi T Yoshikawa Y Okano I Nakanishi R Watanabe M Usui Y Kudo Y

Aims. The localization of necrotic areas has been reported to impact the prognosis and treatment strategy for osteonecrosis of the femoral head (ONFH). Anteroposterior localization of the necrotic area after a femoral neck fracture (FNF) has not been properly investigated. We hypothesize that the change of the weight loading direction on the femoral head due to residual posterior tilt caused by malunited FNF may affect the location of ONFH. We investigate the relationship between the posterior tilt angle (PTA) and anteroposterior localization of osteonecrosis using lateral hip radiographs. Methods. Patients aged younger than 55 years diagnosed with ONFH after FNF were retrospectively reviewed. Overall, 65 hips (38 males and 27 females; mean age 32.6 years (SD 12.2)) met the inclusion criteria. Patients with stage 1 or 4 ONFH, as per the Association Research Circulation Osseous classification, were excluded. The ratios of anterior and posterior viable areas and necrotic areas of the femoral head to the articular surface were calculated by setting the femoral head centre as the reference point. The PTA was measured using Palm’s method. The association between the PTA and viable or necrotic areas of the femoral head was assessed using Spearman’s rank correlation analysis (median PTA 6.0° (interquartile range 3 to 11.5)). Results. We identified a negative correlation between PTA and anterior viable areas (rho −0.477; p = 0.001), and no correlation between PTA and necrotic (rho 0.229; p = 0.067) or posterior viable areas (rho 0.204; p = 0.132). Conclusion. Our results suggest that residual posterior tilt after FNF could affect the anteroposterior localization of necrosis. Cite this article: Bone Jt Open 2024;5(5):394–400


Bone & Joint Research
Vol. 10, Issue 9 | Pages 619 - 628
27 Sep 2021
Maestro-Paramio L García-Rey E Bensiamar F Saldaña L

Aims. To investigate whether idiopathic osteonecrosis of the femoral head (ONFH) is related to impaired osteoblast activities. Methods. We 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. Results. Osteoblasts 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 E. 2. 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. Conclusion. Idiopathic 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


Bone & Joint Research
Vol. 10, Issue 7 | Pages 445 - 458
7 Jul 2021
Zhu S Zhang X Chen X Wang Y Li S Qian W

Aims. The value of core decompression (CD) in the treatment of osteonecrosis of the femoral head (ONFH) remains controversial. We conducted a systematic review and meta-analysis to evaluate whether CD combined with other treatments could improve the clinical and radiological outcomes of ONFH patients compared with CD alone. Methods. We searched the PubMed, Embase, Web of Science, and Cochrane Library databases until June 2020. All randomized controlled trials (RCTs) and clinical controlled trials (CCTs) comparing CD alone and CD combined with other measures (CD + cell therapy, CD + bone grafting, CD + porous tantalum rod, etc.) for the treatment of ONFH were considered eligible for inclusion. The primary outcomes of interest were Harris Hip Score (HHS), ONFH stage progression, structural failure (collapse) of the femoral head, and conversion to total hip arthroplasty (THA). The pooled data were analyzed using Review Manager 5.3 software. Results. A total of 20 studies with 2,123 hips were included (CD alone = 768, CD combined with other treatments = 1,355). The combination of CD with other therapeutic interventions resulted in a higher HHS (mean difference (MD) = 6.46, 95% confidence interval (CI) = 2.10 to 10.83, p = 0.004) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (MD = −10.92, 95% CI = -21.41 to -4.03, p = 0.040) and a lower visual analogue scale (VAS) score (MD = −0.99, 95% CI = -1.56 to -0.42, p < 0.001) than CD alone. For the rates of disease stage progression, 91 (20%) progressed in the intervention group compared to 146 (36%) in the control group (odds ratio (OR) = 0.32, 95% CI = 0.16 to 0.64, p = 0.001). In addition, the intervention group had a more significant advantage in delaying femoral head progression to the collapsed stage (OR = 0.32, 95% CI = 0.17 to 0.61, p < 0.001) and reducing the odds of conversion to THA (OR = 0.35, 95% CI = 0.23 to 0.55, p < 0.001) compared to the control group. There were no serious adverse events in either group. Subgroup analysis showed that the addition of cell therapy significantly improved clinical and radiological outcomes compared to CD alone, and this approach appeared to be more effective than other therapies, particularly in precollapse (stage I to II) ONFH patients. Conclusion. There was marked heterogeneity in the studies. There is a trend towards improved clinical outcomes with the addition of stem cell therapy to CD. Cite this article: Bone Joint Res 2021;10(7):445–458


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 25 - 25
2 Jan 2024
Saldaña L Vilaboa N García-Rey E
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The pathophysiological basis of alterations in trabecular bone of patients with osteonecrosis of the femoral head (ONFH) remains unclear. ONFH has classically been considered a vascular disease with secondary changes in the subchondral bone. However, there is increasing evidence suggesting that ONFH could be a bone disease, since alterations in the functionality of bone tissue distant from the necrotic lesion have been observed. We comparatively studied the transcriptomic profile of trabecular bone obtained from the intertrochanteric region of patients with ONFH without an obvious aetiological factor, and patients with osteoarthritis (OA) undergoing total hip replacement in our Institution. To explore the biological processes that could be affected by ONFH, we compared the transcriptomic profile of trabecular bone from the intertrochanteric region and the femoral head of patients affected by this condition. Differential gene expression was studied using an Affymetrix microarray platform. Transcriptome analysis showed a differential signature in trabecular bone from the intertrochanteric region between patients with ONFH and those with OA. The gene ontology analyses of the genes overexpressed in bone tissue of patients with ONFH revealed a range of enriched biological processes related to cell adhesion and migration and angiogenesis. In contrast, most downregulated transcripts were involved in cell division. Trabecular bone in the intertrochanteric region and in the femoral head also exhibited a differential expression profile. Among the genes differentially expressed, we highlighted those related with cytokine production and immune response. This study identified a set of differently expressed genes in trabecular bone of patients with idiopathic ONFH, which might underlie the pathophysiology of this condition. Acknowledgements: This work was supported by grants PI18/00643 and PI22/00939 from ISCIII-FEDER, Ministerio de Ciencia, Innovación y Universidades (MICINN)-AES


Bone & Joint Research
Vol. 8, Issue 10 | Pages 451 - 458
1 Oct 2019
Kuroda Y Tanaka T Miyagawa T Kawai T Goto K Tanaka S Matsuda S Akiyama H

Objectives. Using a simple classification method, we aimed to estimate the collapse rate due to osteonecrosis of the femoral head (ONFH) in order to develop treatment guidelines for joint-preserving surgeries. Methods. We retrospectively analyzed 505 hips from 310 patients (141 men, 169 women; mean age 45.5 years . (sd. 14.9; 15 to 86)) diagnosed with ONFH and classified them using the Japanese Investigation Committee (JIC) classification. The JIC system includes four visualized types based on the location and size of osteonecrotic lesions on weightbearing surfaces (types A, B, C1, and C2) and the stage of ONFH. The collapse rate due to ONFH was calculated using Kaplan–Meier survival analysis, with radiological collapse/arthroplasty as endpoints. Results. Bilateral cases accounted for 390 hips, while unilateral cases accounted for 115. According to the JIC types, 21 hips were type A, 34 were type B, 173 were type C1, and 277 were type C2. At initial diagnosis, 238/505 hips (47.0%) had already collapsed. Further, the cumulative survival rate was analyzed in 212 precollapsed hips, and the two-year and five-year collapse rates were found to be 0% and 0%, 7.9% and 7.9%, 23.2% and 36.6%, and 57.8% and 84.8% for types A, B, C1, and C2, respectively. Conclusion. Type A ONFH needs no further treatment, but precollapse type C2 ONFH warrants immediate treatment with joint-preserving surgery. Considering the high collapse rate, our study results justify the importance of early diagnosis and intervention in asymptomatic patients with type C2 ONFH. Cite this article: Y. Kuroda, T. Tanaka, T. Miyagawa, T. Kawai, K. Goto, S. Tanaka, S. Matsuda, H. Akiyama. Classification of osteonecrosis of the femoral head: Who should have surgery?. Bone Joint Res 2019;8:451–458. DOI: 10.1302/2046-3758.810.BJR-2019-0022.R1


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 89 - 89
14 Nov 2024
Quero LS Duch CE Vilaboa Díaz N Rey EG
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Introduction. The most frequent diagnosis in young adults undergoing total hip arthroplasty (THA) is osteonecrosis of the femoral head (ONFH), an evolving and disabling condition with an increasing prevalence worldwide. Treatment of ONFH remains a challenge mainly because of a lack of understanding of the disease's pathophysiological basis. This study investigated the biological processes that could be affected by ONFH by comparing the microstructure, histological characteristics and transcriptomic profile of trabecular bone from the femoral head (FH) and the intertrochanteric region (IT) of patients suffering from this condition. Method. A total of 18 patients with idiopathic ONFH undergoing THA in our institution were included. Trabecular bone explants were taken intraoperatively from the FH and the IT of patients. Bone microstructure was examined by micro-computed tomography (micro-CT). After bone sectioning, histological features were studied by hematoxylin and eosin staining. Differential gene expression was investigated using a microarray platform. Result. Micro-CT imaging showed higher trabecular separation and lower trabecular thickness and bone volume in trabecular bone from the FH than from the IT. Histological staining revealed that the number of osteoblasts on the bone surface and the percentage of empty lacunae were higher in trabecular bone from the FH. Transcriptome analysis identified a differential signature in trabecular bone from the FH compared to the IT. The gene ontology analyses of the genes overexpressed in trabecular bone from the FH revealed a range of enriched biological processes related to cell division and immune response. In contrast, most downregulated transcripts were involved in bone formation. Conclusion. This study identified changes in the microarchitecture, histological features and transcriptomic signature of trabecular bone from the FH of patients with idiopathic ONFH, which might underlie the pathophysiology of this condition. This work was supported by PI22/00939 grant from ISCIII-FEDER-MICINN-AES and Luis Alvarez grant from IdiPAZ


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 30 - 30
1 Nov 2021
Maestro L García-Rey E Bensiamar F Saldaña L
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Introduction and Objective. Osteonecrosis of the femoral head (ONFH) is an evolving and disabling condition that often leads to subchondral collapse in late stages. It is the underlying diagnosis for approximately 3%–12% of total hip arthroplasties (THAs) and the most frequent aetiology for young patients undergoing THA. To date, the pathophysiological mechanisms underlying ONFH remain poorly understood. In this study, we investigated whether ONFH without an obvious etiological factor is related to impaired osteoblast activities, as compared to age-matched patients with primary OA. Materials and Methods. We cultured osteoblasts isolated from trabecular bone explants taken from the femoral head of patients with ONFH and from intertrochanteric region of patients with ONFH or with OA and compared their in vitro mineralisation capacity and secretion of paracrine factors. Results. Compared to patients with OA, osteoblasts obtained from the intertrochanteric region of patients with ONFH showed reduced mineralisation capacity, which further decreased in osteoblasts from the femoral head of the same patient. Lower mineralisation of osteoblasts from patients with ONFH correlated with lower mRNA levels of genes encoding osteocalcin and bone sialoprotein and higher osteopontin expression. Osteoblasts from the intertrochanteric region of patients with ONFH secreted lower osteoprtegerin levels than those from patients with OA, resulting in a higher receptor activator of NF-κB ligand (RANKL)-to-osteoprotegerin (OPG) ratio. Notably, the RANKL-to-OPG ratio, as well as the secretion of the proresorptive factors interleukin-6 and prostaglandin E. 2. , was higher in osteoblasts from the femoral head of patients with ONFH than in those from the intertrochanteric region. Conclusions. ONFH is associated with a reduced mineralisation capacity of osteoblasts and increased secretion of proresorptive factors


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 22 - 22
2 Jan 2024
García-Rey E Pérez-Barragans F Saldaña L
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Total hip arthroplasty (THA) outcome in patients with osteonecrosis of the femoral head ONFH) are excellent, however, there is controversy when compared with those in patients with osteoarthritis (OA). Reduced mineralization capacity of osteoblasts of the proximal femur in patients with ONFH could affect implant fixation. We asked if THA fixation in patients with ONFH is worse than in those with OA. We carried out a prospective comparative case (OA)-control (ONFH) study of patients undergoing THA at our hospital between 2017 and 2019. The minimum follow-up was 2 years. Inclusion criteria were patients with uncemented THA, younger than 70 years old, a Dorr femoral type C and idiopathic ONFH. We compared the clinical (Merlé D'Aubigné-Postel score) and radiological results related with implant positioning and fixation. Engh criteria and subsidence were assessed at the immediate postoperative, 12 weeks, 6 months, 12 months and yearly. Osteoblastic activity was determined by mineralization assay on primary cultures of osteoblasts isolated from trabecular bone samples collected from the intertrochanteric area obtained during surgery. Group 1 (ONFH) included 18 patients and group 2 (OA), 22. Average age was 55.9 years old in group 1 and 61.3 in group 2. (p=0.08). There were no differences related with sex, Dorr femoral type or femoral filling. The mean clinical outcome score was 17.1 in group 1 and 16.5 in group 2 (p=0.03). There were no cases of dislocation, infection, or revision surgery in this series. There were 5 cases (28%) of femoral stem subsidence greater than 3mm within 6 first months in group 1 and 1 case (4.5%) in group 2 (p=0.05). Although there were no significant differences related to clinical results, bone fixation was slower, and a greater subsidence was observed in patients with ONFH. Greater femoral stem subsidence was associated with a lower capacity for mineral nodule formation in cultured osteoblasts. The surgical technique could influence THA outcome in patients with reduced mineralization capacity of osteoblasts


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_10 | Pages 5 - 5
1 Oct 2020
Gorman H Jordan E Varady NH Hosseinzadeh S Smith S Chen AF Mont M Iorio R
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Introduction. A staging system has been developed to revise the 1994 ARCO classification for ONFH. The final consensus resulted in the following 4-staged system: stage I—X-ray is normal, but either magnetic resonance imaging or bone scan is positive; stage II—X-ray is abnormal (subtle signs of osteosclerosis, focal osteoporosis, or cystic change in the femoral head) but without any evidence of subchondral fracture, fracture in the necrotic portion, or flattening of the femoral head; stage III—fracture in the subchondral or necrotic zone as seen on X-ray or computed tomography scans. This stage is further divided into stage IIIA (early, femoral head depression ≤2 mm) and stage IIIB (late, femoral head depression >2 mm); and stage IV—X-ray evidence of osteoarthritis with accompanying joint space narrowing, acetabular changes, and/or joint destruction. Radiographs, magnetic resonance imaging (MRI), and computed tomography (CT) scans may all be involved in diagnosing ONFH; however, the optimal diagnostic modality remains unclear. The purpose of this study was to identify: 1) how ONFH is diagnosed at a single academic medical center, and 2) if CT is a necessary modality for diagnosing/staging OFNH. Methods. The EMR was queried for the diagnosis of ONFH between 1/1/2008–12/31/2018 at a single academic medical center. CT and MRI scans were reviewed by the senior author and other contributors. The timing and staging quality of the diagnosis of ONFH were compared between MRI and CT to determine if CT was a necessary component of the ONFH work-up. Results. There were 803 patients with ONFH over the 10 years of study. 382 had CT only, 166 had MRI only, and 255 had both a CT and MRI. Of the 255 patients who had both CT and MRI, 228 actually had ONFH after inspection. A diagnosis of ONFH was made by MRI only in 57% (129/228) while another 21% (48/228) used MRI and CT simultaneously. 22% (51/228) of cases were diagnosed by CT scan first. 94% (48/51) of these cases involved a cancer (CA) diagnoses, the CT scans were used for CA staging and were not helpful with ARCO staging of ONFH. The other 3 cases identified asymptomatic ONFH. MRI scans performed after diagnosis with CT in symptomatic patients were then utilized for staging. Conclusion. Although CT scan was a useful adjunct for diagnosing ONFH during a staging workup for CA, it was not useful for ARCO staging of ONFH and treatment decisions. Based on this retrospective study, CT scan is not necessary when using the Revised ARCO Staging System


Bone & Joint Research
Vol. 10, Issue 8 | Pages 526 - 535
1 Aug 2021
Xin W Yuan S Wang B Qian Q Chen Y

Aims. Circular RNAs (circRNAs) are a novel type of non-coding RNA that plays major roles in the development of diverse diseases including osteonecrosis of the femoral head (ONFH). Here, we explored the impact of hsa_circ_0066523 derived from forkhead box P1 (FOXP1) (also called circFOXP1) on bone mesenchymal stem cells (BMSCs), which is important for ONFH development. Methods. RNA or protein expression in BMSCs was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot, respectively. Cell Counting Kit 8 (CCK8) and 5-ethynyl-2’-deoxyuridine (EdU) were used to analyze cell proliferation. Alkaline phosphatase (ALP) activity, ALP staining, and Alizarin Red S staining were employed to evaluate the osteoblastic differentiation. Chromatin immunoprecipitation (ChIP), luciferase reporter, RNA pull down, and RNA immunoprecipitation (RIP) assays were combined for exploring molecular associations. Results. Circ_0066523 was upregulated in osteogenic induction process of BMSCs. Silencing circ_0066523 restrained the proliferation and osteogenic differentiation of BMSCs. Mechanistically, circ_0066523 activated phosphatidylinositol-4,5-bisphosphate 3-kinase / AKT serine/threonine kinase 1 (PI3K/AKT) pathway via recruiting lysine demethylase 5B (KDM5B) to epigenetically repress the transcription of phosphatase and tensin homolog (PTEN). Functionally, AKT signalling pathway agonist or PTEN knockdown counteracted the effects of silenced circ_0066523 on BMSC proliferation and differentiation. Conclusion. Circ_0066523 promotes the proliferation and differentiation of BMSCs by epigenetically repressing PTEN and therefore activating AKT pathway. This finding might open new avenues for the identification of therapeutic targets for osteoblast differentiation related diseases such as ONFH. Cite this article: Bone Joint Res 2021;10(8):526–535


Bone & Joint Research
Vol. 5, Issue 6 | Pages 276 - 279
1 Jun 2016
Zhu H Gao Y Wang Y Zhang C

Objectives. Circulating exosomes represent novel biomarkers for multiple diseases. In this study, we investigated whether circulating exosome levels could be used as a diagnostic biomarker for steroid-induced osteonecrosis of the femoral head (ONFH). Methods. We assessed the serum exosome level of 85 patients with steroid-induced ONFH and 115 healthy donors by Nanosight detection. We then assessed the diagnostic accuracy of serum exosomes by receiver operating characteristic curve analysis. Results. The circulating exosome level of the ONFH group was significantly lower than that of control group. The area under the curve was 0.72, suggesting that the level of serum exosomes has moderate diagnostic accuracy for steroid-induced ONFH. Conclusion. Circulating exosome levels are valuable in the diagnosis of steroid-induced ONFH. Cite this article: H-Y. Zhu, Y-C. Gao, Y. Wang, C-Q. Zhang. Circulating exosome levels in the diagnosis of steroid-induced osteonecrosis of the femoral head. Bone Joint Res 2016;5:276–279. DOI: 10.1302/2046-3758.56.BJR-2015-0014.R1


The Bone & Joint Journal
Vol. 102-B, Issue 7 | Pages 838 - 844
1 Jul 2020
Chen L Hong G Hong Z Lin T Chen Z Zhang Q He W

Aims. The aim of this study was to report the medium-term outcomes of impaction bone allograft and fibular grafting for osteonecrosis of the femoral head (ONFH) and to define the optimal indications. Methods. A total of 67 patients (77 hips) with ONFH were enrolled in a single centre retrospective review. Success of the procedure was assessed using the Harris Hip Score (HHS) and rate of revision to total hip arthroplasty (THA). Risk factors were studied, including age, aetiology, duration of hip pain, as well as two classification systems (Association Research Circulation Osseous (ARCO) and Japanese Investigation Committee (JIC) systems). Results. After a mean follow-up period of 8.61 years (SD 1.45), 81.3% (52/64) of enrolled cases had a good or excellent HHS at latest follow-up (declining to 76.0% (38/50) for those with more than eight years of follow-up). Overall survival was 92.1% at eight years’ follow-up (95% CI 83.2% to 96.4%). A total of 12 hips (19.0%) failed (reoperation or HHS < 70 points) at final follow-up. Rate of success was adversely affected by increasing age, duration of pain, and more severe disease as measured using the ARCO and JIC classifications, but not by aetiology of the ONFH. Conclusion. We report favourable medium-term results of this procedure. Best outcomes can be expected in patients matching the following indications: younger than 40 years; less 12-month hip pain before surgery; femoral head collapse being less than 2 mm; and integrated lateral wall of femoral head. Cite this article: Bone Joint J 2020;102-B(7):838–844


The Bone & Joint Journal
Vol. 102-B, Issue 7 Supple B | Pages 122 - 128
1 Jul 2020
Sodhi N Acuna A Etcheson J Mohamed N Davila I Ehiorobo JO Jones LC Delanois RE Mont MA

Aims. Earlier studies dealing with trends in the management of osteonecrosis of the femoral head (ONFH) identified an increasing rate of total hip arthroplasties (THAs) and a decreasing rate of joint-preserving procedures between 1992 and 2008. In an effort to assess new trends in the management of this condition, this study evaluated the annual trends of joint-preserving versus arthroplasties for patients aged < or > 50 years old, and the incidence of specific operative management techniques. Methods. A total of 219,371 patients with ONFH were identified from a nationwide database between 1 January 2009 and 31 December 2015. The mean age was 54 years (18 to 90) and 105,298 (48%) were female. The diagnosis was made using International Classification of Disease, Ninth revision, Clinical Modification (ICD-9-CM) and Tenth Revision, Clinical Modification (ICD-10-CM) procedure codes. The percentage of patients managed using each procedure during each year was calculated and compared between years. The trends in the use of the types of procedure were also evaluated. Results. The rate of joint-preserving procedures was significantly higher in patients aged < 50 years compared with those aged > 50 years (4.93% vs 1.52%; p < 0.001). For the overall cohort, rates of arthroplasty were far greater than those for joint-preserving procedures. THA was the most commonly performed procedure (291,114; 94.03%), while osteotomy (3,598; 1.16%), partial arthroplasty (9,171; 2.96%), core decompression (1,200; 0.39%), and bone graft (3,026; 0.98%) were performed markedly less frequently. The annual percentage of patients managed using a THA (93.56% to 89.52%; p < 0.001), resurfacing (1.22% to 0.19%; p < 0.001), and osteotomy (1.31% to 1.05%; p < 0.001) also decreased during the study period. Conclusion. We found that patients with ONFH have been most commonly managed with non-joint-preserving procedures. Our findings provide valuable insight into the current management of this condition and should increase efforts being made to save the hip joint. Cite this article: Bone Joint J 2020;102-B(7 Supple B):122–128


The Bone & Joint Journal
Vol. 96-B, Issue 2 | Pages 259 - 262
1 Feb 2014
Guo KJ Zhao FC Guo Y Li FL Zhu L Zheng W

Corticosteroid use has been implicated in the development of osteonecrosis of the femoral head (ONFH). The exact mechanism and predisposing factors such as age, gender, dosage, type and combination of steroid treatment remain controversial. Between March and July 2003, a total of 539 patients with severe acute respiratory syndrome (SARS) were treated with five different types of steroid. There were 129 men (24%) and 410 women (76%) with a mean age of 33.7 years (21 to 59). Routine screening was undertaken with radiographs, MRI and/or CT to determine the incidence of ONFH. Of the 129 male patients with SARS, 51 (39.5%) were diagnosed as suffering from ONFH, compared with only 79 of 410 female patients (19.3%). The incidence of ONFH in the patients aged between 20 and 49 years was much higher than that of the group aged between 50 and 59 years (25.9% (127 of 491) versus 6.3% (3 of 48); p = 0.018). The incidence of ONFH in patients receiving one type of steroid was 12.5% (21 of 168), which was much lower than patients receiving two different types (28.6%; 96 of 336) or three different types of steroid (37.1%; 13 of 35). Cite this article: Bone Joint J 2014;96-B:259–62


The Bone & Joint Journal
Vol. 99-B, Issue 2 | Pages 175 - 183
1 Feb 2017
Morita D Hasegawa Y Okura T Osawa Y Ishiguro N

Aims. Transtrochanteric rotational osteotomy (TRO) is performed for young patients with non-traumatic osteonecrosis of the femoral head (ONFH) to preserve the hip. We aimed to investigate the long-term outcomes and the risk factors for failure 15 years after this procedure. Patients and Methods. This study included 95 patients (111 hips) with a mean age of 40 years (21 to 64) who underwent TRO for ONFH. The mean follow-up was 18.2 years (3 to 26). Kaplan–Meier survivorship analyses were performed with conversion to total hip arthroplasty (THA) and radiological failure due to secondary collapse of the femoral head or osteoarthritic changes as the endpoint. Multivariate analyses were performed to assess risk factors for each outcome. Results. Survival rates at 15 years with conversion to THA and radiological failure as the endpoint were 59% (95% confidence interval (CI) 49 to 67) and 30% (95% CI 22 to 39), respectively. Necrotic type C2 ONFH (lesions extending laterally to the acetabular edge) (hazards ratio (HR) 3.9) and age > 40 years (HR 2.5) were risk factors for conversion to THA. Stage > 3a ONFH (HR 2.0) and age > 40 years (HR 1.9) were risk factors for radiological failure. Conclusion. The 15 year outcomes after TRO for ONFH are unfavorable because osteoarthritic changes occur after five years post-operatively. Cite this article: Bone Joint J 2017;99-B:175–83


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_12 | Pages 45 - 45
1 Oct 2019
Goodman SB Steere JT Hwang K
Full Access

Background. Surgical treatment for osteonecrosis of the femoral head (ONFH) includes both joint-preserving techniques and joint replacement. Joint preservation is more effective in early-stage ONFH; thus, prompt diagnosis when the femoral head is still salvageable is an important clinical goal. We report a 20-year retrospective study that summarizes the proportion of patients diagnosed with early-stage versus late-stage ONFH at initial presentation to our practice. Methods. Our institutional database was reviewed to identify patients 18–65 years of age who were diagnosed with atraumatic ONFH in our clinic between 1998–2018. The Association Research Circulation Osseous (ARCO) system was used to stage ONFH, based on available imaging. Patients with prior surgical treatment for ONFH were excluded. Results. Four-hundred and thirteen patients and 642 hips with ONFH were identified. At initial presentation, 93 (23%) patients and 229 (37%) hips were diagnosed with stage I or II osteonecrosis. Three hundred and twenty patients (77%) and 403 hips (63%) were diagnosed with stage III or stage IV osteonecrosis. Fifty-eight percent of patients were male, and 56% of patients had bilateral involvement. Average age at presentation was 44 years. Treatments included nonoperative treatment (35%), joint preservation surgery (19%), hip resurfacing (1%), and total hip replacement (45%). Conclusions. More than three-quarters of patients with femoral head ONFH were diagnosed at a late stage. Efforts to improve early detection and prompt referral to orthopaedic surgeons may enable more patients to be diagnosed with early-stage ONFH and improve the success of hip preservation techniques. For any tables or figures, please contact the authors directly


The Bone & Joint Journal
Vol. 95-B, Issue 3 | Pages 320 - 325
1 Mar 2013
Fukushima W Yamamoto T Takahashi S Sakaguchi M Kubo T Iwamoto Y Hirota Y

The systemic use of steroids and habitual alcohol intake are two major causative factors in the development of idiopathic osteonecrosis of the femoral head (ONFH). To examine any interaction between oral corticosteroid use and alcohol intake on the risk of ONFH, we conducted a hospital-based case-control study of 71 cases with ONFH (mean age 45 years (20 to 79)) and 227 matched controls (mean age 47 years (18 to 79)). Alcohol intake was positively associated with ONFH among all subjects: the adjusted odds ratio (OR) of subjects with ≥ 3032 drink-years was 3.93 (95% confidence interval (CI) 1.18 to 13.1) compared with never-drinkers. When stratified by steroid use, the OR of such drinkers was 11.1 (95% CI 1.30 to 95.5) among those who had never used steroids, but 1.10 (95% CI 0.21 to 4.79) among those who had. When we assessed any interaction based on a two-by-two table of alcohol and steroid use, the OR of those non-drinkers who did use steroids was markedly elevated (OR 31.5) compared with users of neither. However, no further increase in OR was noted for the effect of using both (OR 31.6). We detected neither a multiplicative nor an additive interaction (p for multiplicative interaction 0.19; synergy index 0.95), suggesting that the added effect of alcohol may be trivial compared with the overwhelming effect of steroids in the development of ONFH. Cite this article: Bone Joint J 2013;95-B:320–5