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

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

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

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

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

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

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

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

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 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

Osteonecrosis of the femoral head (ONFH) is an ischemic disorder that causes bone and bone marrow necrosis. In spite of many studies, the primary cause of ischemia is still unknown. The purpose of this study is to identify the susceptibility genes in ONFH. We performed a genome-wide association study (GWAS) in 1,602 ONFH cases and 60,000 controls. Stratified GWASs based on the 3 subgroups of ONFH (corticosteroids, alcohol, idiopathic) were also performed. We then evaluated the candidate gene in silico using public databases. Two loci in 12q24.11–12 and 20q12 showed significant association with ONFH. A stratified analysis suggested that the 12q24 locus was associated with ONFH through the drinking capacity. In the 20q12 locus, LINC01370 was the only gene, which functions were related to the plausible biological pathway for the development of ONFH. A novel ONFH locus was identified at chromosome 20q12, and LINC01370 was the best candidate gene in this locus

Aims. We compared the clinical outcomes of curved intertrochanteric varus osteotomy (CVO) with bone impaction grafting (BIG) with CVO alone for the treatment of osteonecrosis of the femoral head (ONFH). Methods. This retrospective comparative study included 81 patients with ONFH; 37 patients (40 hips) underwent CVO with BIG (BIG group) and 44 patients (47 hips) underwent CVO alone (CVO group). Patients in the BIG group were followed-up for a mean of 12.2 years (10.0 to 16.5). Patients in the CVO group were followed-up for a mean of 14.5 years (10.0 to 21.0). Assessment parameters included the Harris Hip Score (HHS), Oxford Hip Score (OHS), Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire (JHEQ), complication rates, and survival rates, with conversion to total hip arthroplasty (THA) and radiological failure as the endpoints. Results. There were no significant differences in preoperative and postoperative HHS or postoperative OHS and JHEQ between the BIG group and the CVO group. Complication rates were comparable between groups. Ten-year survival rates with conversion to THA and radiological failure as the endpoints were not significantly different between groups. Successful CVO (postoperative coverage ratio of more than one-third) exhibited better ten-year survival rates with radiological failure as the endpoint in the BIG group (91.4%) than in the CVO group (77.7%), but this difference was not significant (p = 0.079). Conclusion. Long-term outcomes of CVO with BIG were favourable when proper patient selection and accurate surgery are performed. However, this study did not show improvements in treatment results with the concomitant use of BIG. Cite this article: Bone Joint J 2021;103-B(4):665–671

Introduction. The purpose of this study was to analyze trends in the surgical management of ON in recent years. Specifically, we evaluated the annual prevalences of: 1) joint preserving procedures (osteotomies and core decompression/grafts) and 2) joint non-preserving procedures (total hip arthroplasties [THAs], revision THAs, partial THAs) for the treatment of osteonecrosis of the femoral head (ONFH) between 2009 and 2016. Background. A total of 406,239 ONFH patients who were treated between 2009 and 2016 were identified from a nationwide database. Treatment procedures were extracted using ICD-9-CM and ICD-10-CM procedure codes. Annual rates of each of the above procedures were calculated and the trends in the procedure types were also evaluated. Chi-square tests were performed to compare the annual prevalence of each procedure. The mean annual prevalence over the 8-year study period was calculated for each procedure. Results. Throughout the study period, the number of joint preserving procedures steadily increased by 27%. In the earliest year studied, 2009, 41% (n=19,559) of the total procedures for ONFH were joint-preserving compared to 52% (n=13,715) in 2016. The rates of joint non-preserving procedures decreased (59 to 48%) over the same period (Figure 1). There was a decreasing annual prevalence of THAs (88 to 82%), revision THAs (2.0 to 1.4%), partial THAs (3.4 to 2.3%), osteotomies (4.2 to 3.2%), and core decompression (1.9 to 1.4%) throughout the study period (p<0.001). Throughout the 8-year period, THA was most commonly performed (mean annual prevalence 83%) whereas osteotomies (3.7%), partial THA (2.8%), core decompression/graft (1.9%), and revision THA (1.5%) were less commonly performed. Conclusion. In order to better understand trends in ONFH management, this study evaluated the annual prevalence of 5 commonly performed procedures. Although earlier data indicated decreasing rates of joint preserving procedure, this study found ONFH management has shifted more towards these procedures. For any tables or figures, please contact the authors directly

Introduction. In early stage osteonecrosis of the femoral head (ONFH), core decompression (CD) is often performed; however, approximately 30% of CD cases progress to femoral head collapse. Bone healing can be augmented by preconditioning MSCs (pMSCs) with inflammatory cytokines. Another immunomodulatory approach is the timely resolution of inflammation using cytokines such as IL-4. We investigated the efficacy of pMSC and genetically modified MSCs that over-express IL-4 (IL4-MSCs) on steroid-associated ONFH in rabbits. Methods. Thirty-six male skeletally mature NZW rabbits received methylprednisolone acetate (20mg/kg) IM once 4 weeks before surgery. There were 6 groups:. CD alone – a 3 mm drill hole. + injection into the CD of:. hydrogel (HG) - 200 μl of hydrogel carrier. MSCs–1 million rabbit MSCs. pMSC - LPS (20 μg/ml) + TNFα (20 ng/ml) preconditioned MSCs. IL4-MSCs – rabbit IL-4 over-expressing MSCs. IL4-pMSCs – preconditioned IL-4 over-expressing MSCs. Eight weeks after surgery, femurs were harvested, and evaluated by microCT, biomechanical, and histological analyses. Results. Bone mineral density (BMD) and bone volume fraction (BVF) increased in the pMSC group compared to the CD and MSC groups . outside. of the CD area (p < 0.05, Fig.1). Similarly, the IL4-pMSC group was increased compared to the CD group (p < 0.05). The percentage of empty lacunae in the IL4-MSC group was significantly less than other groups . outside. the CD area (p < 0.05, Fig.2); however, IL4-MSC group had less trabecular bone formation . inside. the CD. The mechanical tests demonstrated no differences. Discussion. This rabbit steroid-associated ONFH model demonstrated that pMSC increased new bone formation after CD; IL4-MSCs that continuously secreted IL-4 decreased the number of empty lacunae . Immunomodulation of bone healing has the potential to improve bone healing after CD for early stage ONFH; these interventions must be applied in a temporally sensitive fashion. For any figures, tables, or references, please contact the authors directly

Osteonecrosis of the femoral head (ONFH) is a painful and disabling condition, which most commonly involves the hips of young patients. But despite of the high incidence, treatment is still has not been definitely identified. We performed a modified muscle pedicle bone graft (MPBG) technique using anterior one-third of gluteus medius (GM) attached to the greater trochanter (GT) in ONFH. The purpose of this study was to evaluate the effectiveness of our technique on ONFH in ARCO stage II and III patients. Between June 2007 and March 2015, 24 hips were treated by our technique, who were able to follow up at least 2 years. The group was consisted of 15 men and 8 women, mean age of 36 years at the time of surgery. Mean follow-up was 5 years. Twenty of 24 hips hips had no progression of necrotic lesions. The postoperative scintigrams showed increased blood flow in the 3 month follow up evaluation. But 4 hips underwent THA at the mean follow-up of 6 years after the surgery, and considered as “failure”. Excluding the 4 failed cases, the mean Harris hip score was improved from 54 points to 85 points at the last follow up. Through our new technique, we showed 83% of survival rate by average of 5 year follow up. And compared to other reports, our technique showed relatively good survival rate and clinical outcomes. Therefore, we suggest this modified technique as one of promising treatment of choices for young patients with ARCO stage II or III ONFH

It has been suggested that transient osteoporosis or the bone marrow oedema syndrome (BMOS) may be the initial phase of osteonecrosis of the femoral head (ONFH) and that there may be a common pathophysiology. In this study, we have assessed the MR images of 200 consecutive patients with ONFH in respect of the BMO pattern in order to test this hypothesis. This pattern was not observed in the early stage of ONFH. The initial abnormal finding detected on the MR images was an abnormal band of intensity at the junction between the necrotic area and the normal bone. Structural damage of the head seems to result in the appearance of the BMO pattern and the development of pain in ONFH. There was no finding to support the existence of a continuum between BMOS and ONFH

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In this study, we aimed to visualize the spatial distribution characteristics of femoral head necrosis using a novel measurement method.

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Successful cell therapy in hip osteonecrosis (ON) may help to avoid ON progression or total hip arthroplasty (THA), but the achieved bone regeneration is unclear. The aim of this study was to evaluate amount and location of bone regeneration obtained after surgical injection of expanded autologous mesenchymal stromal cells from the bone marrow (BM-hMSCs).

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The aim of this study was to evaluate the suitability of the tapered cone stem in total hip arthroplasty (THA) in patients with excessive femoral anteversion and after femoral osteotomy.

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This study aimed to investigate whether the use of CT-based navigation enhances: 1) the accuracy of cup placement; and 2) the achievement rate of required range of motion (ROM). Additionally, we investigated the impact of using a large femoral head and dual-mobility liner on the achievement rates.