Aims. The aim of this study was to determine whether fixation, as opposed to revision arthroplasty, can be safely used to treat reducible Vancouver B type fractures in association with a cemented collarless polished tapered femoral stem (the Exeter). Methods. This retrospective cohort study assessed 152 operatively managed consecutive unilateral Vancouver B fractures involving Exeter stems; 130 were managed with open reduction and internal fixation (ORIF) and 22 with revision arthroplasty. Mean follow-up was 6.5 years (SD 2.6; 3.2 to 12.1). The primary outcome measure was revision of at least one component. Kaplan–Meier survival analysis was performed. Regression analysis was used to identify risk factors for revision following ORIF. Secondary outcomes included any reoperation, complications, blood transfusion, length of hospital stay, and mortality. Results. Fractures (B1 n = 74 (49%); B2 n = 50 (33%); and B3 n = 28 (18%)) occurred at median of 4.2 years (interquartile range (IQR) 1.2 to 9.2) after primary total hip arthroplasty (THA) (n = 138) or hemiarthroplasty (n = 14). Rates of revision and reoperation were significantly higher following revision arthroplasty compared to ORIF for B2 (p = 0.001) and B3 fractures (p = 0.050). Five-year survival was significantly better following ORIF: 92% (95% confidence interval (CI) 86.4% to 97.4%) versus 63% (95% CI 41.7% to 83.3%), p < 0.001. ORIF was associated with reduced blood transfusion requirement and reoperations, but there were no differences in medical complications, hospital stay, or mortality between surgical groups. No independent predictors of revision following ORIF were identified: where the bone-cement interface was intact, fixation of B2 or B3 fractures was not associated with an increased risk of revision. Conclusion. When the bone-cement interface was intact and the fracture was anatomically reducible, all Vancouver B fractures around Exeter stems could be managed with fixation as opposed to revision arthroplasty. Fixation was associated with reduced need for blood transfusion and lower risk of revision surgery compared with revision arthroplasty. Cite this article: Bone Joint J 2021;103-B(2):309–320

Aims. The aim of this study was to radiologically evaluate the quality of cement mantle and alignment achieved with a polished tapered cemented femoral stem inserted through the anterior approach and compared with the posterior approach. Methods. A comparative retrospective study of 115 consecutive hybrid total hip arthroplasties or cemented hemiarthroplasties in 110 patients, performed through anterior (n = 58) or posterior approach (n = 57) using a collarless polished taper-slip femoral stem, was conducted. Cement mantle quality and thickness were assessed in both planes. Radiological outcomes were compared between groups. Results. No significant differences were identified between groups in Barrack grade on the anteroposterior (AP) (p = 0.640) or lateral views (p = 0.306), or for alignment on the AP (p = 0.603) or lateral views (p = 0.254). An adequate cement mantle (Barrack A or B) was achieved in 77.6% (anterior group, n = 45) and in 86% (posterior group, n = 49), respectively. Multivariate analysis revealed factors associated with unsatisfactory cement mantle (Barrack C or D) included higher BMI, left side, and Dorr Type C morphology. A mean cement mantle thickness of ≥ 2 mm was achieved in all Gruen zones for both approaches. The mean cement mantle was thicker in zone 7 (p < 0.001) and thinner in zone 9 for the anterior approach (p = 0.032). Incidence of cement mantle defects between groups was similar (6.9% (n = 4) vs 8.8% (n = 5), respectively; p = 0.489). Conclusion. An adequate cement mantle and good alignment can be achieved using a collarless polished tapered femoral component inserted through the anterior approach. Cite this article: Bone Joint J 2021;103-B(7 Supple B):46–52

Aims. The aim of this study is to report the long-term outcomes of instrumented femoral revisions with impaction allograft bone grafting (IBG) using the X-change femoral revision system at 30 years after introduction of the technique. Methods. We updated the outcomes of our previous study, based on 208 consecutive revisions using IBG and the X-change femoral revision system in combination with a cemented polished stem, performed in our tertiary care institute between 1991 and 2007. Kaplan-Meier survival analyses were used to determine the survival rate of the revisions with endpoint revision for any reason and aseptic loosening. Secondary outcomes were radiological loosening and patient-reported outcome measures. Results. Mean age at revision total hip arthroplasty (THA) was 64.9 years (30 to 86). The most prevalent diagnosis for the femoral revision was aseptic loosening. At review in May 2021, 81 patients (85 hips) were still alive and 118 patients (120 hips; 58%) had died. Three patients (3 hips; 1%) were lost to follow-up at 11, 15, and 16 years after surgery, respectively. Data of all deceased and lost patients were included until final follow-up. The mean follow-up was 13.4 years (0 to 28). During the follow-up, 22 re-revisions were performed. The most common reason for re-revision was infection (n = 12; 54%). The survival with endpoint re-revision for any reason was 86% (95% confidence interval (CI) 79 to 91) at 20 years and 74% (95% CI 43 to 89) at 25 years after surgery. The survival for endpoint re-revision for aseptic loosening was 97% (95% CI 91 to 99) after both 20 and 25 years. Conclusion. We conclude that femoral IBG is a valuable technique that can reconstitute femoral bone loss in the long term. After 25 years of follow-up, few re-revisions for aseptic loosening were required. Also, the overall revision rate is very acceptable at a long follow-up. This technique is especially attractive for younger patients facing femoral revisions with extensive bone loss. Cite this article: Bone Joint J 2022;104-B(9):1039–1046

Aims. Ageing-related incompetence becomes a major hurdle for the clinical translation of adult stem cells in the treatment of osteoarthritis (OA). This study aims to investigate the effect of stepwise preconditioning on cellular behaviours in human mesenchymal stem cells (hMSCs) from ageing patients, and to verify their therapeutic effect in an OA animal model. Methods. Mesenchymal stem cells (MSCs) were isolated from ageing patients and preconditioned with chondrogenic differentiation medium, followed by normal growth medium. Cellular assays including Bromodeoxyuridine / 5-bromo-2'-deoxyuridine (BrdU), quantitative polymerase chain reaction (q-PCR), β-Gal, Rosette forming, and histological staining were compared in the manipulated human mesenchymal stem cells (hM-MSCs) and their controls. The anterior cruciate ligament transection (ACLT) rabbit models were locally injected with two millions, four millions, or eight millions of hM-MSCs or phosphate-buffered saline (PBS). Osteoarthritis Research Society International (OARSI) scoring was performed to measure the pathological changes in the affected joints after staining. Micro-CT analysis was conducted to determine the microstructural changes in subchondral bone. Results. Stepwise preconditioning approach significantly enhanced the proliferation and chondrogenic potential of ageing hMSCs at early passage. Interestingly, remarkably lower immunogenicity and senescence was also found in hM-MSCs. Data from animal studies showed cartilage damage was retarded and subchondral bone remodelling was prevented by the treatment of preconditioned MSCs. The therapeutic effect depended on the number of cells applied to animals, with the best effect observed when treated with eight millions of hM-MSCs. Conclusion. This study demonstrated a reliable and feasible stepwise preconditioning strategy to improve the safety and efficacy of ageing MSCs for the prevention of OA development. Cite this article: Bone Joint Res 2021;10(1):10–21

Aims. Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration. Methods. A total of 24 male New Zealand white rabbits were divided into four groups according to the experimental materials. Allogenic adipose-derived mesenchymal stem cells (AMSCs) were cultured and seeded evenly in the collagen/chitosan sheet to form cell sheet as periosteum. Simultaneously, allogenic AMSCs were seeded onto alginate beads and were cultured to differentiate to endothelial-like cells to form vascularized bone construct (VBC). The cell sheet was wrapped onto VBC to create a vascularized bone-periosteum construct (VBPC). Four different experimental materials – acellular construct, VBC, non-vascularized bone-periosteum construct, and VBPC – were then implanted in bilateral L4-L5 intertransverse space. At 12 weeks post-surgery, the bone-forming capacities were determined by CT, biomechanical testing, histology, and immunohistochemistry staining analyses. Results. At 12 weeks, the VBPC group significantly increased new bone formation volume compared with the other groups. Biomechanical testing demonstrated higher torque strength in the VBPC group. Notably, the haematoxylin and eosin, Masson’s trichrome, and immunohistochemistry-stained histological results revealed that VBPC promoted neovascularization and new bone formation in the spine fusion areas. Conclusion. The tissue-engineered VBPC showed great capability in promoting angiogenesis and osteogenesis in vivo. It may provide a novel approach to create a superior blood supply and nutritional environment to overcome the deficits of current artificial bone graft substitutes. Cite this article: Bone Joint Res 2023;12(12):722–733

Aims. To test the hypothesis that reseeded anterior cruciate ligament (ACL)-derived cells have a better ability to survive and integrate into tendon extracellular matrix (ECM) and accelerate the ligamentization process, compared to adipose-derived mesenchymal stem cells (ADMSCs). Methods. Acellularized tibialis allograft tendons were used. Tendons were randomly reseeded with ACL-derived cells or ADMSCs. ACL-derived cells were harvested and isolated from remnants of ruptured ACLs during reconstruction surgery and cultured at passage three. Cell suspensions (200 µl) containing 2 × 10. 6. ACL-derived cells or ADMSCs were prepared for the purpose of reseeding. At days 1, 3, and 7 post-reseeding, graft composites were assessed for repopulation with histological and immunohistochemical analysis. Matrix protein contents and gene expression levels were analyzed. Results. In the graft reseeded with ACL-derived cells, a large number of elongated cells that integrated into the matrix were evident at day 3 and day 7. However, in the graft reseeded with ADMSCs, only a small number of elongated cells were found integrated into the matrix. Immunofluorescence for Ki-67 and type I collagen confirmed the pronounced production of type I collagen by Ki-67-positive ACL-derived cells integrated into the ECM. A messenger RNA (mRNA) expression assay demonstrated significantly higher gene expression levels of types I (p = 0.013) and III (p = 0.050) collagen in the composites reseeded with ACL-derived cells than ADMSCs. Conclusion. ACL-derived cells, when reseeded to acellularized tendon graft, demonstrated earlier better survival and integration in the tendon ECM and resulted in higher gene expression levels of collagen, which may be essential to the normal ligamentization process compared to ADMSCs. Cite this article: Bone Joint Res 2022;11(11):777–786

Aims. Compared with primary total hip arthroplasty (THA), revision surgery can be challenging. The cement-in-cement femoral revision technique involves removing a femoral component from a well-fixed femoral cement mantle and cementing a new stem into the original mantle. This technique is widely used and when carried out for the correct indications, is fast, relatively inexpensive and carries a reduced short-term risk for the patient compared with the alternative of removing well-fixed cement. We report the outcomes of this procedure when two commonly used femoral stems are used. Patients and Methods. We identified 1179 cement-in-cement stem revisions involving an Exeter or a Lubinus stem reported to the Swedish Hip Arthroplasty Register (SHAR) between January 1999 and December 2015. Kaplan-Meier survival analysis was performed. Results. Survivorship is reported up to six years and was better in the Exeter group (91% standard deviation (. sd). 2.8% versus 85% . sd. 5.0%) (p = 0.02). There was, however, no significant difference in the survival of the stem and risk of re-revision for any reason (p = 0.58) and for aseptic loosening (p = 0.97), between revisions in which the Exeter stem (94% . sd. 2.2%; 98% . sd. 1.6%) was used compared with those in which the Lubinus stem (95% . sd. 3.2%; 98% . sd.  2.2%) was used. The database did not allow identification of whether a further revision was indicated for loosening of the acetabular or femoral component or both. Conclusion. The cement-in-cement technique for revision of the femoral component gave promising results using both designs of stem, six years post-operatively. Cite this article: Bone Joint J 2017;99-B(4 Supple B):27–32

Aims. The aims of this study were to evaluate the incidence of reoperation (all cause and specifically for periprosthetic femoral fracture (PFF)) and mortality, and associated risk factors, following a hemiarthroplasty incorporating a cemented collarless polished taper slip stem (PTS) for management of an intracapsular hip fracture. Methods. This retrospective study included hip fracture patients aged 50 years and older treated with Exeter (PTS) bipolar hemiarthroplasty between 2019 and 2022. Patient demographics, place of domicile, fracture type, delirium status, American Society of Anesthesiologists (ASA) grade, length of stay, and mortality were collected. Reoperation and mortality were recorded up to a median follow-up of 29.5 months (interquartile range 12 to 51.4). Cox regression was performed to evaluate independent risk factors associated with reoperation and mortality. Results. The cohort consisted of 1,619 patients with a mean age of 82.2 years (50 to 104), of whom 1,100 (67.9%) were female. In total, 29 patients (1.8%) underwent a reoperation; 12 patients (0.7%) sustained a PFF during the observation period (United Classification System (UCS)-A n = 2; UCS-B n = 5; UCS-C n = 5), of whom ten underwent surgical management. Perioperative delirium was independently associated with the occurrence of PFF (hazard ratio (HR) 5.92; p = 0.013) and surgery for UCS-B PFF (HR 21.7; p = 0.022). Neither all-cause reoperation nor PFF-related surgery was independently associated with mortality (HR 0.66; p = 0.217 and HR 0.38; p = 0.170, respectively). Perioperative delirium, male sex, older age, higher ASA grade, and pre-fracture residential status were independently associated with increased mortality risk following hemiarthroplasty (p < 0.001). Conclusion. The cumulative incidence of PFF at four years was 1.1% in elderly patients following cemented PTS hemiarthroplasty for a hip fracture. Perioperative delirium was independently associated with a PFF. However, reoperation for PPF was not independently associated with patient mortality after adjusting for patient-specific factors. Cite this article: Bone Jt Open 2024;5(4):269–276

Aims. Astragalus polysaccharide (APS) participates in various processes, such as the enhancement of immunity and inhibition of tumours. APS can affect osteoporosis (OP) by regulating the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs). This study was designed to elucidate the mechanism of APS in hBMSC proliferation and osteoblast differentiation. Methods. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were performed to determine the expression of microRNA (miR)-760 and ankyrin repeat and FYVE domain containing 1 (ANKFY1) in OP tissues and hBMSCs. Cell viability was measured using the Cell Counting Kit-8 assay. The expression of cyclin D1 and osteogenic marker genes (osteocalcin (OCN), alkaline phosphatase (ALP), and runt-related transcription factor 2 (RUNX2)) was evaluated using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Mineral deposits were detected through Alizarin Red S staining. In addition, Western blotting was performed to detect the ANKFY1 protein levels following the regulation of miR-760. The relationship between miR-760 and ANKFY1 was determined using a luciferase reporter assay. Results. The expression of miR-760 was upregulated in OP tissues, whereas ANKFY1 expression was downregulated. APS stimulated the differentiation and proliferation of hBMSCs by: increasing their viability; upregulating the expression levels of cyclin D1, ALP, OCN, and RUNX2; and inducing osteoblast mineralization. Moreover, APS downregulated the expression of miR-760. Overexpression of miR-760 was found to inhibit the promotive effect of APS on hBMSC differentiation and proliferation, while knockdown of miR-760 had the opposite effect. ANKFY1 was found to be the direct target of miR-760. Additionally, ANKFY1 participated in the APS-mediated regulation of miR-760 function in hBMSCs. Conclusion. APS promotes the osteogenic differentiation and proliferation of hBMSCs. Moreover, APS alleviates the effects of OP by downregulating miR-760 and upregulating ANKFY1 expression. Cite this article: Bone Joint Res 2023;12(8):476–485

Aims. This study investigates the effects of intra-articular injection of adipose-derived mesenchymal stem cells (AdMSCs) and platelet-rich plasma (PRP) on lameness, pain, and quality of life in osteoarthritic canine patients. Methods. With informed owner consent, adipose tissue collected from adult dogs diagnosed with degenerative joint disease was enzymatically digested and cultured to passage 1. A small portion of cells (n = 4) surplus to clinical need were characterized using flow cytometry and tri-lineage differentiation. The impact and degree of osteoarthritis (OA) was assessed using the Liverpool Osteoarthritis in Dogs (LOAD) score, Modified Canine Osteoarthritis Staging Tool (mCOAST), kinetic gait analysis, and diagnostic imaging. Overall, 28 joints (25 dogs) were injected with autologous AdMSCs and PRP. The patients were followed up at two, four, eight, 12, and 24 weeks. Data were analyzed using two related-samples Wilcoxon signed-rank or Mann-Whitney U tests with statistical significance set at p < 0.05. Results. AdMSCs demonstrated stem cell-like characteristics. LOAD scores were significantly lower at week 4 compared with preinjection (p = 0.021). The mCOAST improved significantly after three months (p = 0.001) and six months (p = 0.001). Asymmmetry indices decreased from four weeks post-injection and remained significantly lower at six months (p = 0.025). Conclusion. These improvements in quality of life, reduction in pain on examination, and improved symmetry in dogs injected with AdMSCs and PRP support the effectiveness of this combined treatment for symptom modification in canine OA for six months. Cite this article: Bone Joint Res 2021;10(10):650–658

Aims. To compare long-term survival of all-cemented and hybrid total hip arthroplasty (THA) using the Exeter Universal stem. Methods. Details of 1,086 THAs performed between 1999 and 2005 using the Exeter stem and either a cemented (632) or uncemented acetabular component (454) were collected from local records and the New Zealand Joint Registry. A competing risks regression survival analysis was performed with death as the competing risk with adjustments made for age, sex, approach, and bearing. Results. There were 61 revisions (9.7%; 0.82 revisions/100 observed component years, (OCYs)) in the all-cemented group and 18 (4.0%; 0.30/100 OCYs) in the hybrid group. The cumulative incidence of revision at 18 years was 12.1% for cemented and 5.2% for hybrids. There was a significantly greater risk of revision for all-cemented compared with hybrids (unadjusted sub-hazard ratio (SHR) 2.44; p = 0.001), and of revision for loosening, wear, or osteolysis (unadjusted SHR 3.77; p < 0.001). After adjustment, the increased risk of all-cause revision did not reach significance at age 70 years and above. The advantage for revision for loosening, wear, and osteolysis remained at all ages. Conclusion. This study supports the use of uncemented acetabular fixation when used in combination with the Exeter stem with improved survivorship for revision for aseptic loosening, wear, and osteolysis at all ages and for all-cause revision in patients less than 70 years. Cite this article: Bone Joint J 2020;102-B(4):414–422

Aims. Although good clinical outcomes have been reported for monolithic tapered, fluted, titanium stems (TFTS), early results showed high rates of subsidence. Advances in stem design may mitigate these concerns. This study reports on the use of a current monolithic TFTS for a variety of indications. Methods. A multi-institutional retrospective study of all consecutive total hip arthroplasty (THA) and revision total hip arthroplasty (rTHA) patients who received the monolithic TFTS was conducted. Surgery was performed by eight fellowship-trained arthroplasty surgeons at four institutions. A total of 157 hips in 153 patients at a mean follow-up of 11.6 months (SD7.8) were included. Mean patient age at the time of surgery was 67.4 years (SD 13.3) and mean body mass index (BMI) was 28.9 kg/m. 2. (SD 6.5). Outcomes included intraoperative complications, one-year all-cause re-revisions, and subsidence at postoperative time intervals (two weeks, six weeks, six months, nine months, and one year). Results. There were eight intraoperative complications (4.9%), six of which were intraoperative fractures; none occurred during stem insertion. Six hips (3.7%) underwent re-revision within one year; only one procedure involved removal of the prosthesis due to infection. Mean total subsidence at latest follow-up was 1.64 mm (SD 2.47). Overall, 17 of 144 stems (11.8%) on which measurements could be performed had >5 mm of subsidence, and 3/144 (2.1%) had >10 mm of subsidence within one year. A univariate regression analysis found that additional subsidence after three months was minimal. A multivariate regression analysis found that subsidence was not significantly associated with periprosthetic fracture as an indication for surgery, the presence of an extended trochanteric osteotomy (ETO), Paprosky classification of femoral bone loss, stem length, or type of procedure performed (i.e. full revision vs conversion/primary). Conclusion. Advances in implant design, improved trials, a range of stem lengths and diameters, and high offset options mitigate concerns of early subsidence and dislocation with monolithic TFTS, making them a valuable option for femoral revision. Cite this article: Bone Joint J 2020;102-B(2):191–197

Aims. A number of methods have been described to remove a well-fixed humeral implant as part of revision shoulder arthroplasty. These include the use of cortical windows and humeral osteotomies. The router bit extraction technique uses a high-speed router bit to disrupt the bone-implant interface. The implant is then struck in a retrograde fashion with a square-tip impactor and mallet. The purpose of this study was to determine the characteristics and frequency of the different techniques needed for the removal of a well-fixed humeral stem in revision shoulder arthroplasty. Patients and Methods. Between 2010 and 2018, 288 revision shoulder arthroplasty procedures requiring removal of a well-fixed humeral component were carried out at a tertiary referral centre by a single surgeon. The patient demographics, indications for surgery, and method of extraction were collected. Results. Of the 288 revisions, 284 humeral stems (98.6%) were removed using the router bit extraction technique alone. Four humeral stems (1.39%) required an additional cortical window. Humeral osteotomy was not necessary in any procedure. Most of the humeral stems removed (78.8%) were cementless. Of the four humeral stems that required a cortical window, three involved removal of a hemiarthroplasty. Two were cemented and two were cementless. Conclusion. The router bit extraction technique removed a well-fixed humeral component in a very high proportion of patients (98.6%). This method allows surgeons to avoid more invasive approaches involving a cortical window or humeral osteotomy, and their associated complications. Cite this article: Bone Joint J 2019;101-B:1280–1284

Aims. In the repair of condylar cartilage injury, synovium-derived mesenchymal stem cells (SMSCs) migrate to an injured site and differentiate into cartilage. This study aimed to confirm that histone deacetylase (HDAC) inhibitors, which alleviate arthritis, can improve chondrogenesis inhibited by IL-1β, and to explore its mechanism. Methods. SMSCs were isolated from synovium specimens of patients undergoing temporomandibular joint (TMJ) surgery. Chondrogenic differentiation potential of SMSCs was evaluated in vitro in the control, IL-1β stimulation, and IL-1β stimulation with HDAC inhibitors groups. The effect of HDAC inhibitors on the synovium and condylar cartilage in a rat TMJ arthritis model was evaluated. Results. Interleukin (IL)-1β inhibited the chondrogenic differentiation potential of SMSCs, while the HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and panobinostat (LBH589), attenuated inhibition of IL-1β-induced SMSC chondrogenesis. Additionally, SAHA attenuated the destruction of condylar cartilage in rat TMJ arthritis model. IL-6 (p < 0.001) and matrix metalloproteinase 13 (MMP13) (p = 0.006) were significantly upregulated after IL-1β stimulation, while SAHA and LBH589 attenuated IL-6 and MMP13 expression, which was upregulated by IL-1β in vitro. Silencing of IL-6 significantly downregulated MMP13 expression and attenuated IL-1β-induced chondrogenesis inhibition of SMSCs. Conclusion. HDAC inhibitors SAHA and LBH589 attenuated chondrogenesis inhibition of SMSC induced by IL-1β in TMJ, and inhibition of IL-6/MMP13 pathway activation contributes to this biological progress. This study provides a theoretical basis for the application of HDAC inhibitors in the treatment of TMJ arthritis. Cite this article: Bone Joint Res 2022;11(1):40–48

Cell therapies hold significant promise for the treatment of injured or diseased musculoskeletal tissues. However, despite advances in research, there is growing concern about the increasing number of clinical centres around the world that are making unwarranted claims or are performing risky biological procedures. Such providers have been known to recommend, prescribe, or deliver so called ‘stem cell’ preparations without sufficient data to support their true content and efficacy. In this annotation, we outline the current environment of stem cell-based treatments and the strategies of marketing directly to consumers. We also outline the difficulties in the regulation of these clinics and make recommendations for best practice and the identification and reporting of illegitimate providers. Cite this article: Bone Joint J 2020;102-B(2):148–154

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. Bone tissue engineering is one of the fastest growing branches in modern bioscience. New methods are being developed to achieve higher grades of mineral deposition by osteogenically inducted mesenchymal stem cells. In addition to well established monolayer cell culture models, 3D cell cultures for stem cell-based osteogenic differentiation have become increasingly attractive to promote in vivo bone formation. One of the main problems of scaffold-based osteogenic cell cultures is the difficulty in quantifying the amount of newly produced extracellular mineral deposition, as a marker for new bone formation, without destroying the scaffold. In recent studies, we were able to show that . 99m. Tc-methylene diphosphonate (. 99m. Tc-MDP), a gamma radiation-emitting radionuclide, can successfully be applied as a reliable quantitative marker for mineral deposition as this tracer binds with high affinity to newly produced hydroxyapatite (HA). Methods. Within the present study, we evaluated whether this promising new method, using . 99m. Tc-hydroxydiphosphonate (. 99m. Tc-HDP), can be used to quantify the amount of newly formed extracellular HA in a 3D cell culture model. Highly porous collagen type II scaffolds were seeded with 1 × 106 human mesenchymal stem cells (hMSCs; n = 6) and cultured for 21 days in osteogenic media (group A – osteogenic (OSM) group) and in parallel in standard media (group B – negative control (CNTRL) group). After incubation with . 99m. Tc-HDP, the tracer uptake, reflected by the amount of emitted gamma counts, was measured. Results. We saw a higher uptake (up to 15-fold) of the tracer in the OSM group A compared with the CNTRL group B. Statistical analysis of the results (Student`s t-test) revealed a significantly higher amount of emitted gamma counts in the OSM group (p = 0.048). Qualitative and semi-quantitative analysis by Alizarin Red staining confirmed the presence of extracellular HA deposition in the OSM group. Conclusion. Our data indicate that . 99m. Tc-HDP labelling is a promising tool to track and quantify non-destructive local HA deposition in 3D stem cell cultures. Cite this article: T. L. Grossner, U. Haberkorn, T. Gotterbarm. . 99m. Tc-Hydroxydiphosphonate quantification of extracellular matrix mineralization in 3D human mesenchymal stem cell cultures. Bone Joint Res 2019;8:333–341. doi: 10.1302/2046-3758.87.BJR-2017-0248.R1

Aims. Femoral stems with exchangeable (modular) necks were introduced to offer surgeons an increased choice when determining the version, offset and length of the femoral neck during total hip arthroplasty (THA). It was hoped that this would improve outcomes and reduce complications, particularly dislocation. In 2010, the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) first reported an increased rate of revision after primary THA using femoral stems with an exchangeable neck. The aim of this study was to provide a more comprehensive up-to-date analysis of primary THA using femoral stems with exchangeable and fixed necks. Materials and Methods. The data included all primary THA procedures performed for osteoarthritis (OA), reported to the AOANJRR between 01 September 1999 and 31 December 2014. There were 9289 femoral stems with an exchangeable neck and 253 165 femoral stems with a fixed neck. The characteristics of the patients and prostheses including the bearing surface and stem/neck metal combinations were examined using Cox proportional hazard ratios (HRs) and Kaplan-Meier estimates of survivorship. . Results. It was found that prostheses with an exchangeable neck had a higher rate of revision and this was evident regardless of the bearing surface or the size of the femoral head. Exchangeable neck prostheses with a titanium stem and a cobalt-chromium neck had a significantly higher rate of revision compared with titanium stem/titanium neck combinations (HR 1.83, 95% confidence interval 1.49 to 2.23, p < 0.001). Revisions were higher for these combinations compared with femoral stems with a fixed neck. Conclusion . There appears to be little evidence to support the continued use of prostheses with an exchangeable neck in primary THA undertaken for OA. Cite this article: Bone Joint J 2017;99-B:766–73