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

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

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

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

Objectives. The primary purpose of this meta-analysis was to determine whether statin usage could reduce the risk of glucocorticoid-related osteonecrosis in animal models. Methods. A systematic literature search up to May 2015 was carried out using the PubMed, Ovid, EBM reviews, ISI Web of Science, EBSCO, CBM, CNKI databases with the term and boolean operators: statins and osteonecrosis in all fields. Risk ratio (RR), as the risk estimate of specific outcome, was calculated along with 95% confidence intervals (CI). The methodological quality of individual studies was assessed using a quantitative tool based on the updated Stroke Therapy Academic Industry Roundtable (STAIR) recommendations. Results. A total of 11 eligible studies were included according to predetermined criteria. The pooled data demonstrated that animals with statin usage, either alone or combined with other treatments, were at a decreased risk of developing glucocorticoid-related osteonecrosis (RR = 2.06, 95% confidence interval (CI) 1.71 to 2.50). Moreover, subgroup analysis revealed that compared with statins alone, statins combined with other treatments significantly decreased the risk of osteonecrosis (RR = 1.23, 95% CI 1.02 to 1.47). However, we could find no significant risk difference for different gender, or for different time points. Conclusions. The present study suggests that statins combined with other treatments are efficient in preventing the development of glucocorticoid-related osteonecrosis in animals. These results might shed light on clinical practice when glucocorticoids are prescribed, and could be further investigated in high-quality clinical trials. Cite this article: Z. Yang, H. Liu, D. Li, X. Xie, T. Qin, J. Ma, P. Kang. The efficacy of statins in preventing glucocorticoid-related osteonecrosis in animal models: A meta-analysis. Bone Joint Res 2016;5:393–402. DOI: 10.1302/2046-3758.59.2000500

Aims. 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). Methods. A total of 20 patients with small and medium-size symptomatic stage II femoral head ON treated with 140 million BM-hMSCs through percutaneous forage in the EudraCT 2012-002010-39 clinical trial were retrospectively evaluated through preoperative and postoperative (three and 12 months) MRI. Then, 3D reconstruction of the original lesion and the observed postoperative residual damage after bone regeneration were analyzed and compared per group based on treatment efficacy. Results. The mean preoperative lesion volume was 18.7% (SD 10.2%) of the femoral head. This reduced to 11.6% (SD 7.5%) after three months (p = 0.015) and 3.7% (SD 3%) after one year (p < 0.001). Bone regeneration in healed cases represented a mean 81.2% (SD 13.8%) of the initial lesion volume at one year. Non-healed cases (n = 1 stage progression; n = 3 THAs) still showed bone regeneration but this did not effectively decrease the ON volume. A lesion size under mean 10% (SD 6%) of the femoral head at three months predicted no ON stage progression at one year. Regeneration in the lateral femoral head (C2 under Japanese Investigation Committee (JCI) classification) and in the central and posterior regions of the head was predominant in cases without ON progression. Conclusion. Bone regeneration was observed in osteonecrotic femoral heads three months after expanded autologous BM-hMSC injection, and the volume and location of regeneration indicated the success of the therapy. Cite this article: Bone Joint Res 2022;11(12):881–889

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

Cite this article: Bone Joint Res 2023;12(1):5–8.

Aims

The aim of this study was to perform a cross-cultural adaptation of Oxford Hip Score (OHS) to Indonesian, and to evaluate its psychometric properties.

Aims. To systematically review the predominant complication rates and changes to patient-reported outcome measures (PROMs) following osteochondral allograft (OCA) transplantation for shoulder instability. Methods. This systematic review, following PRISMA guidelines and registered in PROSPERO, involved a comprehensive literature search using PubMed, Embase, Web of Science, and Scopus. Key search terms included “allograft”, “shoulder”, “humerus”, and “glenoid”. The review encompassed 37 studies with 456 patients, focusing on primary outcomes like failure rates and secondary outcomes such as PROMs and functional test results. Results. A meta-analysis of primary outcomes across 17 studies revealed a dislocation rate of 5.1% and an increase in reoperation rates from 9.3% to 13.7% post-publication bias adjustment. There was also a noted rise in conversion to total shoulder arthroplasty and incidence of osteoarthritis/osteonecrosis over longer follow-up periods. Patient-reported outcomes and functional tests generally showed improvement, albeit with notable variability across studies. A concerning observation was the consistent presence of allograft resorption, with rates ranging from 33% to 80%. Comparative studies highlighted similar efficacy between distal tibial allografts and Latarjet procedures in most respects, with some differences in specific tests. Conclusion. OCA transplantation presents a promising treatment option for shoulder instability, effectively addressing both glenoid and humeral head defects with favourable patient-reported outcomes. These findings advocate for the inclusion of OCA transplantation in treatment protocols for shoulder instability, while also emphasizing the need for further high-quality, long-term research to better understand the procedure’s efficacy profile. Cite this article: Bone Jt Open 2024;5(7):570–580

Aims. Osteoarthritis (OA) is characterized by persistent destruction of articular cartilage. It has been found that microRNAs (miRNAs) are closely related to the occurrence and development of OA. The purpose of the present study was to investigate the mechanism of miR-486 in the development and progression of OA. Methods. The expression levels of miR-486 in cartilage were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN), matrix metalloproteinase (MMP)-13, and a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS4) in SW1353 cells at both messenger RNA (mRNA) and protein levels was determined by qRT-PCR, western blot, and enzyme-linked immunosorbent assay (ELISA). Double luciferase reporter gene assay, qRT-PCR, and western blot assay were used to determine whether silencing information regulator 6 (SIRT6) was involved in miR-486 induction of chondrocyte-like cells to a more catabolic phenotype. Results. Compared with osteonecrosis, the expression of miR-486 was significantly upregulated in cartilage from subjects with severe OA. In addition, overexpressed miR-486 promoted a catabolic phenotype in SW1353 cells by upregulating the expressions of ADAMTS4 and MMP-13 and down-regulating the expressions of COL2A1 and ACAN. Conversely, inhibition of miR-486 had the opposite effect. Furthermore, overexpression of miR-486 significantly inhibited the expression of SIRT6, confirming that SIRT6 is a direct target of miR-486. Moreover, SW1353 cells were transfected with small interfering RNA (si)-SIRT6 and it was found that SIRT6 was involved in and inhibited miR-486-induced changes to SW1353 gene expression. Conclusion. Our results indicate that miR-486 promotes a catabolic phenotype in SW1353 cells in OA by targeting SIRT6. Our findings might provide a potential therapeutic target and theoretical basis for OA. Cite this article: Bone Joint Res 2021;10(7):459–466

Aims. Bone marrow-derived mesenchymal stem cells obtained from bone marrow aspirate concentrate (BMAC) with platelet-rich plasma (PRP), has been used as an adjuvant to hip decompression. Early results have shown promise for hip preservation in patients with osteonecrosis (ON) of the femoral head. The purpose of the current study is to examine the mid-term outcome of this treatment in patients with precollapse corticosteroid-induced ON of the femoral head. Methods. In all, 22 patients (35 hips; 11 males and 11 females) with precollapse corticosteroid-induced ON of the femoral head underwent hip decompression combined with BMAC and PRP. Mean age and BMI were 43 years (SD 12) and 31 kg/m² (SD 6), respectively, at the time of surgery. Survivorship free from femoral head collapse and total hip arthroplasty (THA) and risk factors for progression were evaluated at minimum five-years of clinical follow-up with a mean follow-up of seven years (5 to 8). Results. Survivorship free from femoral head collapse and THA for any reason was 84% and 67% at seven years postoperatively, respectively. Risk factors for conversion to THA included a high preoperative modified Kerboul angle (grade 3 or 4) based on preoperative MRI (hazard ratio (HR) 3.96; p = 0.047) and corticosteroid use at the time of decompression (HR 4.15; p = 0.039). The seven-year survivorship for patients with grade 1 or 2 Kerboul angles for conversion to THA for articular collapse, and THA for any reason, were 96% and 72%, respectively, versus THA for articular collapse and THA for any reason in patients with grade 3 or 4 Kerboul angles of 40% (p = 0.003) and 40% (p = 0.032). Conclusion. At seven years, hip decompression augmented with BMAC and PRP provided a 67% survivorship free from THA in patients with corticosteroid-induced ON. Ideal candidates for this procedure are patients with low preoperative Kerboul angles and can stop corticosteroid treatment prior to decompression. Cite this article: Bone Jt Open 2021;2(11):926–931

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

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

Aims

Total hip arthroplasty (THA) is considered the preferred treatment for displaced proximal femoral neck fractures. However, in many countries this option is economically unviable. To improve outcomes in financially disadvantaged populations, we studied the technique of concomitant valgus hip osteotomy and operative fixation (VOOF). This prospective serial study compares two treatment groups: VOOF versus operative fixation alone with cannulated compression screws (CCSs).

Aims

Isolated acetabular liner exchange with a highly crosslinked polyethylene (HXLPE) component is an option to address polyethylene wear and osteolysis following total hip arthroplasty (THA) in the presence of a well-fixed acetabular shell. The liner can be fixed either with the original locking mechanism or by being cemented within the acetabular component. Whether the method used for fixation of the HXLPE liner has any bearing on the long-term outcomes is still unclear.

Aims

It is important to analyze objectively the hammering sound in cup press-fit technique in total hip arthroplasty (THA) in order to better understand the change of the sound during impaction. We hypothesized that a specific characteristic would present in a hammering sound with successful fixation. We designed the study to quantitatively investigate the acoustic characteristics during cementless cup impaction in THA.

Aims

It is important to analyze objectively the hammering sound in cup press-fit technique in total hip arthroplasty (THA) in order to better understand the change of the sound during impaction. We hypothesized that a specific characteristic would present in a hammering sound with successful fixation. We designed the study to quantitatively investigate the acoustic characteristics during cementless cup impaction in THA.