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

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. Hip arthroplasty aims to accurately recreate joint biomechanics. Considerable attention has been paid to vertical and horizontal offset, but femoral head centre in the anteroposterior (AP) plane has received little attention. This study investigates the accuracy of restoration of joint centre of rotation in the AP plane. Methods. Postoperative CT scans of 40 patients who underwent unilateral uncemented total hip arthroplasty were analyzed. Anteroposterior offset (APO) and femoral anteversion were measured on both the operated and non-operated sides. Sagittal tilt of the femoral stem was also measured. APO measured on axial slices was defined as the perpendicular distance between a line drawn from the anterior most point of the proximal femur (anterior reference line) to the centre of the femoral head. The anterior reference line was made parallel to the posterior condylar axis of the knee to correct for rotation. Results. Overall, 26/40 hips had a centre of rotation displaced posteriorly compared to the contralateral hip, increasing to 33/40 once corrected for sagittal tilt, with a mean posterior displacement of 7 mm. Linear regression analysis indicated that stem anteversion needed to be increased by 10.8° to recreate the head centre in the AP plane. Merely matching the native version would result in a 12 mm posterior displacement. Conclusion. This study demonstrates the significant incidence of posterior displacement of the head centre in uncemented hip arthroplasty. Effects of such displacement include a reduction in impingement free range of motion, potential alterations in muscle force vectors and lever arms, and impaired proprioception due to muscle fibre reorientation. Cite this article: Bone Joint Res 2022;11(3):180–188

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. 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.

Objectives. An experimental piglet model induces avascular necrosis (AVN) and deformation of the femoral head but its secondary effects on the developing acetabulum have not been studied. The aim of this study was to assess the development of secondary acetabular deformation following femoral head ischemia. Methods. Intracapsular circumferential ligation at the base of the femoral neck and sectioning of the ligamentum teres were performed in three week old piglets. MRI was then used for qualitative and quantitative studies of the acetabula in operated and non-operated hips in eight piglets from 48 hours to eight weeks post-surgery. Specimen photographs and histological sections of the acetabula were done at the end of the study. . Results. The operated-side acetabula were wider, shallower and misshapen, with flattened labral edges. At eight weeks, increased acetabular cartilage thickness characterised the operated sides compared with non-operated sides (p < 0.001, ANOVA). The mean acetabular width on the operated side was increased (p = 0.015) while acetabular depth was decreased anteriorly (p = 0.007) and posteriorly (p = 0.44). The cartilage was thicker, with delayed acetabular bone formation, and showed increased vascularisation with fibrosis laterally and focal degenerative changes involving chondrocyte hypocellularity, chondrocyte cloning, peripheral pannus formation and surface fibrillation. . Conclusions. We demonstrate that femoral head AVN in the young growing piglet also induced, and was coupled with, secondary malformation in acetabular shape affecting both articular and adjacent pelvic cartilage structure, and acetabular bone. The femoral head model inducing AVN can also be applied to studies of acetabular maldevelopment, which is less well understood in terms of developing hip malformation. Cite this article: Bone Joint Res 2014;3:130–8

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

Objectives. The use of ceramic femoral heads in total hip arthroplasty (THA) has increased due to their proven low bearing wear characteristics. Ceramic femoral heads are also thought to reduce wear and corrosion at the head-stem junction with titanium (Ti) stems when compared with metal heads. We sought to evaluate taper damage of ceramic compared with metal heads when paired with cobalt chromium (CoCr) alloy stems in a single stem design. Methods. This retrieval study involved 48 total hip arthroplasties (THAs) with CoCr V40 trunnions paired with either CoCr (n = 21) or ceramic (n = 27) heads. The taper junction of all hips was evaluated for fretting/corrosion damage and volumetric material loss using a roundness-measuring machine. We used linear regression analysis to investigate taper damage differences after adjusting for potential confounding variables. Results. We measured median taper material loss rates of 0.210 mm. 3. /year (0.030 to 0.448) for the metal head group and 0.084 mm. 3. /year (0.059 to 0.108) for the ceramic group. The difference was not significant (p = 0.58). Moreover, no significant correlation between material loss and implant or patient factors (p > 0.05) was found. Conclusions. Metal heads did not increase taper damage on CoCr trunnions compared with ceramic heads from the same hip design. The amount of material released at the taper junctions was very low when compared with available data regarding CoCr/Ti coupling in metal-on-metal bearings. Cite this article: A. Di Laura, H. Hothi, J. Henckel, I. Swiatkowska, M. H. L. Liow, Y-M. Kwon, J. A. Skinner, A. J. Hart. Retrieval analysis of metal and ceramic femoral heads on a single CoCr stem design. Bone Joint Res 2017;6:–350. DOI: 10.1302/2046-3758.65.BJR-2016-0325.R1

Objectives . We aimed to determine the effect of surgical approach on the histology of the femoral head following resurfacing of the hip. Methods. We performed a histological assessment of the bone under the femoral component taken from retrieval specimens of patients having revision surgery following resurfacing of the hip. We compared the number of empty lacunae in specimens from patients who had originally had a posterior surgical approach with the number in patients having alternative surgical approaches. Results. We found a statistically significant increase in the percentage of empty lacunae in retrieval specimens from patients who had the posterior approach compared with other surgical approaches (p < 0.001). . Conclusions. This indicates that the vascular compromise that occurs during the posterior surgical approach does have long-term effects on the bone of the femoral head, even if it does not cause overt avascular necrosis. Cite this article: Bone Joint Res 2013;2:200–5

Introduction. The objective of this study was to determine if a synthetic bone substitute would provide results similar to bone from osteoporotic femoral heads during in vitro testing with orthopaedic implants. If the synthetic material could produce results similar to those of the osteoporotic bone, it could reduce or eliminate the need for testing of implants on bone. Methods. Pushout studies were performed with the dynamic hip screw (DHS) and the DHS Blade in both cadaveric femoral heads and artificial bone substitutes in the form of polyurethane foam blocks of different density. The pushout studies were performed as a means of comparing the force displacement curves produced by each implant within each material. Results. The results demonstrated that test material with a density of 0.16 g/cm. 3. (block A) produced qualitatively similar force displacement curves for the DHS and qualitatively and quantitatively similar force displacement curves for the DHS Blade, whereas the test material with a density of 0.08 g/cm. 3. (block B) did not produce results that were predictive of those recorded within the osteoporotic cadaveric femoral heads. Conclusion. This study demonstrates that synthetic material with a density of 0.16 g/cm. 3. can provide a good substitute for cadaveric osteoporotic femoral heads in the testing of implants. However we do recognise that no synthetic material can be considered as a definitive substitute for bone, therefore studies performed with artificial bone substrates may need to be validated by further testing with a small bone sample in order to produce conclusive results

Aims. In this study, we aimed to visualize the spatial distribution characteristics of femoral head necrosis using a novel measurement method. Methods. We retrospectively collected CT imaging data of 108 hips with non-traumatic osteonecrosis of the femoral head from 76 consecutive patients (mean age 34.3 years (SD 8.1), 56.58% male (n = 43)) in two clinical centres. The femoral head was divided into 288 standard units (based on the orientation of units within the femoral head, designated as N[Superior], S[Inferior], E[Anterior], and W[Posterior]) using a new measurement system called the longitude and latitude division system (LLDS). A computer-aided design (CAD) measurement tool was also developed to visualize the measurement of the spatial location of necrotic lesions in CT images. Two orthopaedic surgeons independently performed measurements, and the results were used to draw 2D and 3D heat maps of spatial distribution of necrotic lesions in the femoral head, and for statistical analysis. Results. The results showed that the LLDS has high inter-rater reliability. As illustrated by the heat map, the distribution of Japanese Investigation Committee (JIC) classification type C necrotic lesions exhibited clustering characteristics, with the lesions being concentrated in the northern and eastern regions, forming a hot zone (90% probability) centred on the N4-N6E2, N3-N6E units of outer ring blocks. Statistical results showed that the distribution difference between type C2 and type C1 was most significant in the E1 and E2 units and, combined with the heat map, indicated that the spatial distribution differences at N3-N6E1 and N1-N3E2 units are crucial in understanding type C1 and C2 necrotic lesions. Conclusion. The LLDS can be used to accurately measure the spatial location of necrotic lesions and display their distribution characteristics. Cite this article: Bone Joint Res 2024;13(6):294–305

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. While cementless fixation offers potential advantages over cemented fixation, such as a shorter operating time, concerns linger over its higher cost and increased risk of periprosthetic fractures. If the risk of fracture can be forecasted, it would aid the shared decision-making process related to cementless stems. Our study aimed to develop and validate predictive models of periprosthetic femoral fracture (PPFF) necessitating revision and reoperation after elective total hip arthroplasty (THA). Methods. We included 154,519 primary elective THAs from the Swedish Arthroplasty Register (SAR), encompassing 21 patient-, surgical-, and implant-specific features, for model derivation and validation in predicting 30-day, 60-day, 90-day, and one-year revision and reoperation due to PPFF. Model performance was tested using the area under the curve (AUC), and feature importance was identified in the best-performing algorithm. Results. The Lasso regression excelled in predicting 30-day revisions (area under the receiver operating characteristic curve (AUC) = 0.85), while the Gradient Boosting Machine (GBM) model outperformed other models by a slight margin for all remaining endpoints (AUC range: 0.79 to 0.86). Predictive factors for revision and reoperation were identified, with patient features such as increasing age, higher American Society of Anesthesiologists grade (> III), and World Health Organization obesity classes II to III associated with elevated risks. A preoperative diagnosis of idiopathic necrosis increased revision risk. Concerning implant design, factors such as cementless femoral fixation, reverse-hybrid fixation, hip resurfacing, and small (< 35 mm) or large (> 52 mm) femoral heads increased both revision and reoperation risks. Conclusion. This is the first study to develop machine-learning models to forecast the risk of PPFF necessitating secondary surgery. Future studies are required to externally validate our algorithm and assess its applicability in clinical practice. Cite this article: Bone Joint Res 2025;14(1):46–57

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

Objectives. Little is known about tissue changes underlying bone marrow lesions (BMLs) in non-weight-bearing joints with osteoarthritis (OA). Our aim was to characterize BMLs in OA of the hand using dynamic histomorphometry. We therefore quantified bone turnover and angiogenesis in subchondral bone at the base of the thumb, and compared the findings with control bone from hip OA. Methods. Patients with OA at the base of the thumb, or the hip, underwent preoperative MRI to assess BMLs, and tetracycline labelling to determine bone turnover. Three groups were compared: trapezium bones removed by trapeziectomy from patients with thumb base OA (n = 20); femoral heads with (n = 24); and those without (n = 9) BMLs obtained from patients with hip OA who underwent total hip arthroplasty. Results. All trapezium bones demonstrated MRI-defined BMLs. Compared with femoral heads without BMLs, the trapezia demonstrated significantly higher bone turnover (mean . sd. 0.2 (0.1) versus 0.01 (0.01) µm. 3. /µm. 2. /day), mineralizing surface (18.5% (13.1) versus 1.4% (1.3)) and vascularity (5.2% (1.1) versus 1.2% (0.6)). Femoral heads with BMLs exhibited higher bone turnover (0.3 (0.2) versus 0.2 (0.1) µm. 3. /µm. 2. /day), a higher mineralization rate (26.6% (10.6) versus 18.6% (11.9)) and greater trabecular thickness (301.3 µm (108) versus 163.6 µm (24.8)) than the trapezia. Conclusion. Bone turnover and angiogenesis were enhanced in BMLs of both the thumb base and hip OA, of which the latter exhibited the highest bone turnover. Thus, the increase in bone turnover in weight-bearing joints like the hip may be more pronounced than less mechanically loaded osteoarthritic joints demonstrating BMLs. The histological changes observed may explain the water signal from BMLs on MRI. Cite this article: M. Shabestari, N. J. Kise, M. A. Landin, S. Sesseng, J. C. Hellund, J. E. Reseland, E. F. Eriksen, I. K. Haugen. Enhanced angiogenesis and increased bone turnover characterize bone marrow lesions in osteoarthritis at the base of the thumb. Bone Joint Res 2018;7:406–413. DOI: 10.1302/2046-3758.76.BJR-2017-0083.R3

Aims

Research on hip biomechanics has analyzed femoroacetabular contact pressures and forces in distinct hip conditions, with different procedures, and used diverse loading and testing conditions. The aim of this scoping review was to identify and summarize the available evidence in the literature for hip contact pressures and force in cadaver and in vivo studies, and how joint loading, labral status, and femoral and acetabular morphology can affect these biomechanical parameters.

Aims

cAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect.