Objectives. Platelet-rich plasma (PRP) is being used increasingly often in the clinical setting to treat tendon-related pathologies. Yet the optimal PRP preparations to promote tendon healing in different patient populations are poorly defined. Here, we sought to determine whether increasing the concentration of platelet-derived proteins within a derivative of PRP, platelet lysate (PL), enhances tenocyte proliferation and migration in vitro, and whether the mitogenic properties of PL change with donor age. Methods. Concentrated PLs from both young (< 50 years) and aged (> 50 years) donors were prepared by exposing pooled PRP to a series of freeze-thaw cycles followed by dilution in plasma, and the levels of several platelet-derived proteins were measured using multiplex immunoassay technology. Human tenocytes were cultured with PLs to simulate a clinically relevant PRP treatment range, and cell growth and migration were assessed using DNA quantitation and gap closure assays, respectively. Results. Platelet-derived protein levels increased alongside higher PL concentrations, and PLs from both age groups improved tenocyte proliferation relative to control conditions. However, PLs from aged donors yielded a dose-response relationship in tenocyte behaviour, with higher PL concentrations resulting in increased tenocyte proliferation and migration. Conversely, no significant differences in tenocyte behaviour were detected when increasing the concentration of PLs from younger donors. Conclusion. Higher PL concentrations, when prepared from the PRP of aged but not young donors, were more effective than lower PL concentrations at promoting tenocyte proliferation and migration in vitro. Cite this article: D. R. Berger, C. J. Centeno, N. J. Steinmetz. Platelet lysates from aged donors promote human tenocyte proliferation and migration in a concentration-dependent manner. Bone Joint Res 2019;8:32–40. DOI: 10.1302/2046-3758.81.BJR-2018-0164.R1

Aims

The aim of this study was to report the outcomes of different treatment options for glenoid loosening following reverse shoulder arthroplasty (RSA) at a minimum follow-up of two years.

Aims. Medial pivot (MP) total knee arthroplasties (TKAs) were designed to mimic native knee kinematics with their deep medial congruent fitting of the tibia to the femur almost like a ball-on-socket, and a flat lateral part. GMK Sphere is a novel MP implant. Our primary aim was to study the migration pattern of the tibial tray of this TKA. Methods. A total of 31 patients were recruited to this single-group radiostereometric analysis (RSA) study and received a medial pivot GMK Sphere TKA. The distributions of male patients versus female patients and right versus left knees were 21:10 and 17:14, respectively. Mean BMI was 29 kg/m. 2. (95% confidence interval (CI) 27 to 30) and mean age at surgery was 63 years (95% CI 61 to 66). Maximum total point motions (MTPMs), medial, proximal, and anterior translations and transversal, internal, and varus rotations were calculated at three, 12, and 24 months. Patient-reported outcome measure data were also retrieved. Results. MTPMs at three, 12, and 24 months were 1.0 mm (95% CI 0.8 to 1.2), 1.3 mm (95% CI 0.9 to 1.7), and 1.4 mm (0.8 to 2.0), respectively. The Forgotten Joint Score was 79 (95% CI 39 to 95) and Knee Injury and Osteoarthritis Outcome Score obtained at two years was 94 (95% CI 81 to 100), 86 (95% CI 75 to 93), 94 (95% CI 88 to 100), 69 (95% CI 48 to 88), and 81 (95% CI59 to 100) for Pain, Symptoms, Activities of Daily Living, Sport & Recreation, and Quality of Life, respectively. Conclusion. In conclusion, we found that the mean increase in MTPM was lower than 0.2 mm between 12 and 24 months and thus apparently stable. Yet the GMK Sphere had higher migration at one and two years than anticipated. Based on current RSA data, we therefore cannot conclude on the long-term performance of the implant, pending further assessment. Cite this article: Bone Jt Open 2021;2(9):737–744

Objectives. The paradoxical migration of the femoral neck element (FNE) superomedially against gravity, with respect to the intramedullary component of the cephalomedullary device, is a poorly understood phenomenon increasingly seen in the management of pertrochanteric hip fractures with the intramedullary nail. The aim of this study was to investigate the role of bidirectional loading on the medial migration phenomenon, based on unique wear patterns seen on scanning electron microscopy of retrieved implants suggestive of FNE toggling. Methods. A total of 18 synthetic femurs (Sawbones, Vashon Island, Washington) with comminuted pertrochanteric fractures were divided into three groups (n = 6 per group). Fracture fixation was performed using the Proximal Femoral Nail Antirotation (PFNA) implant (Synthes, Oberdorf, Switzerland; n = 6). Group 1 was subjected to unidirectional compression loading (600 N), with an elastomer (70A durometer) replacing loose fracture fragments to simulate surrounding soft-tissue tensioning. Group 2 was subjected to bidirectional loading (600 N compression loading, 120 N tensile loading), also with the elastomer replacing loose fracture fragments. Group 3 was subjected to bidirectional loading (600 N compression loading, 120 N tensile loading) without the elastomer. All constructs were tested at 2 Hz for 5000 cycles or until cut-out occurred. The medial migration distance (MMD) was recorded at the end of the testing cycles. Results. The MMDs for Groups 1, 2, and 3 were 1.02 mm, 6.27 mm, and 5.44 mm respectively, with reliable reproduction of medial migration seen in all groups. Bidirectional loading groups showed significantly higher MMDs compared with the unidirectional loading group (p < 0.01). Conclusion. Our results demonstrate significant contributions of bidirectional cyclic loading to the medial migration phenomenon in cephalomedullary nail fixation of pertrochanteric hip fractures. Cite this article: G. W. Law, Y. R. Wong, A. K-S. Yew, A. C. T. Choh, J. S. B. Koh, T. S. Howe. Medial migration in cephalomedullary nail fixation of pertrochanteric hip fractures: A biomechanical analysis using a novel bidirectional cyclic loading model. Bone Joint Res 2019;8:313–322. DOI: 10.1302/2046-3758.87.BJR-2018-0271.R1

Aims. Reimers migration percentage (MP) is a key measure to inform decision-making around the management of hip displacement in cerebral palsy (CP). The aim of this study is to assess validity and inter- and intra-rater reliability of a novel method of measuring MP using a smart phone app (HipScreen (HS) app). Methods. A total of 20 pelvis radiographs (40 hips) were used to measure MP by using the HS app. Measurements were performed by five different members of the multidisciplinary team, with varying levels of expertise in MP measurement. The same measurements were repeated two weeks later. A senior orthopaedic surgeon measured the MP on picture archiving and communication system (PACS) as the gold standard and repeated the measurements using HS app. Pearson’s correlation coefficient (r) was used to compare PACS measurements and all HS app measurements and assess validity. Intraclass correlation coefficient (ICC) was used to assess intra- and inter-rater reliability. Results. All HS app measurements (from 5 raters at week 0 and week 2 and PACS rater) showed highly significant correlation with the PACS measurements (p < 0.001). Pearson’s correlation coefficient (r) was constantly over 0.9, suggesting high validity. Correlation of all HS app measures from different raters to each other was significant with r > 0.874 and p < 0.001, which also confirms high validity. Both inter- and intra-rater reliability were excellent with ICC > 0.9. In a 95% confidence interval for repeated measurements, the deviation of each specific measurement was less than 4% MP for single measurer and 5% for different measurers. Conclusion. The HS app provides a valid method to measure hip MP in CP, with excellent inter- and intra-rater reliability across different medical and allied health specialties. This can be used in hip surveillance programmes by interdisciplinary measurers. Cite this article: Bone Jt Open 2023;4(5):363–369

Aims. The primary objective of this study was to compare migration of the cemented ATTUNE fixed bearing cruciate retaining tibial component with the cemented Press-Fit Condylar (PFC)-sigma fixed bearing cruciate retaining tibial component. The secondary objectives included comparing clinical and radiological outcomes and Patient Reported Outcome Measures (PROMs). Methods. A single blinded randomized, non-inferiority study was conducted including 74 patients. Radiostereometry examinations were made after weight bearing, but before hospital discharge, and at three, six, 12, and 24 months postoperatively. PROMS were collected preoperatively and at three, six, 12, and 24 months postoperatively. Radiographs for measuring radiolucencies were collected at two weeks and two years postoperatively. Results. The overall migration (mean maximum total point motion (MPTM)) at two years was comparable: mean 1.13 mm (95% confidence interval (CI), 0.97 to 1.30) for the ATTUNE and 1.16 mm (95% CI, 0.99 to 1.35) for the PFC-sigma. At two years, the mean backward tilting was -0.43° (95% CI, -0.65 to -0.21) for the ATTUNE and 0.08° (95% CI -0.16 to 0.31), for the PFC-sigma. Overall migration between the first and second postoperative year was negligible for both components. The clinical outcomes and PROMs improved compared with preoperative scores and were not different between groups. Radiolucencies at the implant-cement interface were mainly seen below the medial baseplate: 17% in the ATTUNE and 3% in the PFC-sigma at two weeks, and at two years 42% and 9% respectively (p = 0.001). Conclusion. In the first two postoperative years the initial version of the ATTUNE tibial component was not inferior with respect to overall migration, although it showed relatively more backwards tilting and radiolucent lines at the implant-cement interface than the PFC-sigma. The version of the ATTUNE tibial component examined in this study has subsequently undergone modification by the manufacturer. Level of Evidence: 1 (randomized controlled clinical trial). Cite this article: Bone Joint J 2020;102-B(9):1158–1166

Aims. Proliferation, migration, and differentiation of anterior cruciate ligament (ACL) remnant and surrounding cells are fundamental processes for ACL reconstruction; however, the interaction between ACL remnant and surrounding cells is unclear. We hypothesized that ACL remnant cells preserve the capability to regulate the surrounding cells’ activity, collagen gene expression, and tenogenic differentiation. Moreover, extracorporeal shock wave (ESW) would not only promote activity of ACL remnant cells, but also enhance their paracrine regulation of surrounding cells. Methods. Cell viability, proliferation, migration, and expression levels of Collagen-I (COL-I) A1, transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF) were compared between ACL remnant cells untreated and treated with ESW (0.15 mJ/mm. 2. , 1,000 impulses, 4 Hz). To evaluate the subsequent effects on the surrounding cells, bone marrow stromal cells (BMSCs)’ viability, proliferation, migration, and levels of Type I Collagen, Type III Collagen, and tenogenic gene (Scx, TNC) expression were investigated using coculture system. Results. ESW-treated ACL remnant cells presented higher cell viability, proliferation, migration, and increased expression of COL-I A1, TGF-β, and VEGF. BMSC proliferation and migration rate significantly increased after coculture with ACL remnant cells with and without ESW stimulation compared to the BMSCs alone group. Furthermore, ESW significantly enhanced ACL remnant cells’ capability to upregulate the collagen gene expression and tenogenic differentiation of BMSCs, without affecting cell viability, TGF-β, and VEGF expression. Conclusion. ACL remnant cells modulated activity and differentiation of surrounding cells. The results indicated that ESW enhanced ACL remnant cells viability, proliferation, migration, and expression of collagen, TGF-β, VEGF, and paracrine regulation of BMSC proliferation, migration, collagen expression, and tenogenesis. Cite this article: Bone Joint Res 2020;9(8):457–467

Objectives. Cellular movement and relocalisation are important for many physiologic properties. Local mesenchymal stem cells (MSCs) from injured tissues and circulating MSCs aid in fracture healing. Cytokines and chemokines such as Stromal cell-derived factor 1(SDF-1) and its receptor chemokine receptor type 4 (CXCR4) play important roles in maintaining mobilisation, trafficking and homing of stem cells from bone marrow to the site of injury. We investigated the differences in migration of MSCs from the femurs of young, adult and ovariectomised (OVX) rats and the effect of CXCR4 over-expression on their migration. Methods. MSCs from young, adult and OVX rats were put in a Boyden chamber to establish their migration towards SDF-1. This was compared with MSCs transfected with CXCR4, as well as MSCs differentiated to osteoblasts. Results. MSCs from OVX rats migrate significantly (p < 0.05) less towards SDF-1 (9%, . sd. 5%) compared with MSCs from adult (15%, . sd. 3%) and young rats (25%, . sd. 4%). Cells transfected with CXCR4 migrated significantly more towards SDF-1 compared with non-transfected cells, irrespective of whether these cells were from OVX (26.5%, . sd. 4%), young (47%, . sd. 17%) or adult (21%, . sd. 4%) rats. Transfected MSCs differentiated to osteoblasts express CXCR4 but do not migrate towards SDF-1. Conclusions. MSC migration is impaired by age and osteoporosis in rats, and this may be associated with a significant reduction in bone formation in osteoporotic patients. The migration of stem cells can be ameliorated by upregulating CXCR4 levels which could possibly enhance fracture healing in osteoporotic patients. Cite this article: A. Sanghani-Kerai, M. Coathup, S. Samazideh, P. Kalia, L. Di Silvio, B. Idowu, G. Blunn. Osteoporosis and ageing affects the migration of stem cells and this is ameliorated by transfection with CXCR4. Bone Joint Res 2017;6:–365. DOI: 10.1302/2046-3758.66.BJR-2016-0259.R1

Objectives. This study aimed to assess the effect of age and osteoporosis on the proliferative and differentiating capacity of bone-marrow-derived mesenchymal stem cells (MSCs) in female rats. We also discuss the role of these factors on expression and migration of cells along the C-X-C chemokine receptor type 4 (CXCR-4) / stromal derived factor 1 (SDF-1) axis. Methods. Mesenchymal stem cells were harvested from the femora of young, adult, and osteopenic Wistar rats. Cluster of differentiation (CD) marker and CXCR-4 expression was measured using flow cytometry. Cellular proliferation was measured using Alamar Blue, osteogenic differentiation was measured using alkaline phosphatase expression and alizarin red production, and adipogenic differentiation was measured using Oil red O. Cells were incubated in Boyden chambers to quantify their migration towards SDF-1. Data was analyzed using a Student’s t-test, where p-values < 0.05 were considered significant. Results. CD marker expression and proliferation of the MSCs from the three groups was not significantly different. The young MSCs demonstrated significantly increased differentiation into bone and fat and superior migration towards SDF-1. The migration of SDF-1 doubled with young rats compared with the adult rats (p = 0.023) and it was four times higher when compared with cells isolated from ovariectomized (OVX) osteopenic rats (p = 0.013). Conclusion. Young rat MSCs are significantly more responsive to osteogenic differentiation, and, contrary to other studies, also demonstrated increased adipogenic differentiation compared with cells from adult and ostopenic rats. Young-rat-derived cells also showed superior migration towards SDF-1 compared with MSCs from OVX and adult control rats. Cite this article: A. Sanghani-Kerai, L. Osagie-Clouard, G. Blunn, M. Coathup. The influence of age and osteoporosis on bone marrow stem cells from rats. Bone Joint Res 2018;7:289–297. DOI: 10.1302/2046-3758.74.BJR-2017-0302.R1

Aims. To explore the synovial expression of mucin 1 (MUC1) and its role in rheumatoid arthritis (RA), as well as the possible downstream mechanisms. Methods. Patients with qualified synovium samples were recruited from a RA cohort. Synovium from patients diagnosed as non-inflammatory orthopaedic arthropathies was obtained as control. The expression and localization of MUC1 in synovium and fibroblast-like synoviocytes were assessed by immunohistochemistry and immunofluorescence. Small interfering RNA and MUC1 inhibitor GO-203 were adopted for inhibition of MUC1. Lysophosphatidic acid (LPA) was used as an activator of Rho-associated pathway. Expression of inflammatory cytokines, cell migration, and invasion were evaluated using quantitative real-time polymerase chain reaction (PCR) and Transwell chamber assay. Results. A total of 63 RA patients and ten controls were included. Expression of MUC1 was observed in both the synovial lining and sublining layer. The percentage of MUC1+ cells in the lining layer of synovium was significantly higher in RA than that in control, and positively correlated to joint destruction scores of RA. Meanwhile, MUC1+ cells in the sublining layer were positively correlated to the Krenn subscore of inflammatory infiltration. Knockdown of MUC1, rather than GO-203 treatment, ameliorated the expression of proinflammatory cytokines, cell migration, and invasion of rheumatoid synoviocytes. Knockdown of MUC1 decreased expression of RhoA, Cdc42, and Rac1. Treatment with LPA compromised the inhibition of migration and invasion, but not inflammation, of synoviocytes by MUC1 knockdown. Conclusion. Upregulated MUC1 promotes the aggression of rheumatoid synoviocytes via Rho guanosine triphosphatases (GTPases), thereby facilitating synovitis and joint destruction during the pathological process of RA. Cite this article: Bone Joint Res 2022;11(9):639–651

Aims. Highly polished stems with force-closed design have shown satisfactory clinical results despite being related to relatively high early migration. It has been suggested that the minimal thickness of cement mantles surrounding the femoral stem should be 2 mm to 4 mm to avoid aseptic loosening. The line-to-line cementing technique of the femoral stem, designed to achieve stem press-fit, challenges this opinion. We compared the migration of a highly polished stem with force-closed design by standard and line-to-line cementing to investigate whether differences in early migration of the stems occur in a clinical study. Methods. In this single-blind, randomized controlled, clinical radiostereometric analysis (RSA) study, the migration pattern of the cemented Corail hip stem was compared between line-to-line and standard cementing in 48 arthroplasties. The primary outcome measure was femoral stem migration in terms of rotation and translation around and along with the X-, Y-, and Z- axes measured using model-based RSA at three, 12, and 24 months. A linear mixed-effects model was used for statistical analysis. Results. Results from mixed model analyses revealed a lower mean retroversion for line-to-line (0.72° (95% confidence interval (CI) 0.38° to 1.07°; p < 0.001), but no significant differences in subsidence between the techniques (-0.15 mm (95% CI -0.53 to 0.227; p = 0.429) at 24 months. Radiolucent lines measuring < 2 mm wide were found in three and five arthroplasties cemented by the standard and line-to-line method, respectively. Conclusion. The cemented Corail stem with a force-closed design seems to settle earlier and better with the line-to-line cementing method, although for subsidence the difference was not significant. However, the lower rate of migration into retroversion may reduce the wear and cement deformation, contributing to good long-term fixation and implant survival. Cite this article: Bone Joint J 2022;104-B(1):19–26

Aims. The Exeter short stem was designed for patients with Dorr type A femora and short-term results are promising. The aim of this study was to evaluate the minimum five-year stem migration pattern of Exeter short stems in comparison with Exeter standard stems. Methods. In this case-control study, 25 patients (22 female) at mean age of 78 years (70 to 89) received cemented Exeter short stem (case group). Cases were selected based on Dorr type A femora and matched first by Dorr type A and then age to a control cohort of 21 patients (11 female) at mean age of 74 years (70 to 89) who received with cemented Exeter standard stems (control group). Preoperatively, all patients had primary hip osteoarthritis and no osteoporosis as confirmed by dual X-ray absorptiometry scanning. Patients were followed with radiostereometry for evaluation of stem migration (primary endpoint), evaluation of cement quality, and Oxford Hip Score. Measurements were taken preoperatively, and at three, 12, and 24 months and a minimum five-year follow-up. Results. At three months, subsidence of the short stem -0.87 mm (95% confidence interval (CI) -1.07 to -0.67) was lower compared to the standard stem -1.59 mm (95% CI -1.82 to -1.36; p < 0.001). Both stems continued a similar pattern of subsidence until five-year follow-up. At five-year follow-up, the short stem had subsided mean -1.67 mm (95% CI -1.98 to -1.36) compared to mean -2.67 mm (95% CI -3.03 to -2.32) for the standard stem (p < 0.001). Subsidence was not influenced by preoperative bone quality (osteopenia vs normal) or cement mantle thickness. Conclusion. The standard Exeter stem had more early subsidence compared with the short Exeter stem in patients with Dorr type A femora, but thereafter a similar migration pattern of subsidence until minimum five years follow-up. Both the standard and the short Exeter stems subside. The standard stem subsides more compared to the short stem in Dorr type A femurs. Subsidence of the Exeter stems was not affected by cement mantle thickness. Cite this article: Bone Jt Open 2023;4(7):507–515

Aims. Hip disease is common in children with cerebral palsy (CP) and can decrease quality of life and function. Surveillance programmes exist to improve outcomes by treating hip disease at an early stage using radiological surveillance. However, studies and surveillance programmes report different radiological outcomes, making it difficult to compare. We aimed to identify the most important radiological measurements and develop a core measurement set (CMS) for clinical practice, research, and surveillance programmes. Methods. A systematic review identified a list of measurements previously used in studies reporting radiological hip outcomes in children with CP. These measurements informed a two-round Delphi study, conducted among orthopaedic surgeons and specialist physiotherapists. Participants rated each measurement on a nine-point Likert scale (‘not important’ to ‘critically important’). A consensus meeting was held to finalize the CMS. Results. Overall, 14 distinct measurements were identified in the systematic review, with Reimer’s migration percentage being the most frequently reported. These measurements were presented over the two rounds of the Delphi process, along with two additional measurements that were suggested by participants. Ultimately, two measurements, Reimer’s migration percentage and femoral head-shaft angle, were included in the CMS. Conclusion. This use of a minimum standardized set of measurements has the potential to encourage uniformity across hip surveillance programmes, and may streamline the development of tools, such as artificial intelligence systems to automate the analysis in surveillance programmes. This core set should be the minimum requirement in clinical studies, allowing clinicians to add to this as needed, which will facilitate comparisons to be drawn between studies and future meta-analyses. Cite this article: Bone Jt Open 2023;4(11):825–831

Aims. Despite limited clinical scientific backing, an additional trochanteric stabilizing plate (TSP) has been advocated when treating unstable trochanteric fractures with a sliding hip screw (SHS). We aimed to explore whether the TSP would result in less post operative fracture motion, compared to SHS alone. Methods. Overall, 31 patients with AO/OTA 31-A2 trochanteric fractures were randomized to either a SHS alone or a SHS with an additional TSP. To compare postoperative fracture motion, radiostereometric analysis (RSA) was performed before and after weightbearing, and then at four, eight, 12, 26, and 52 weeks. With the “after weightbearing” images as baseline, we calculated translations and rotations, including shortening and medialization of the femoral shaft. Results. Similar migration profiles were observed in all directions during the course of healing. At one year, eight patients in the SHS group and 12 patients in the TSP group were available for analysis, finding a clinically non-relevant, and statistically non-significant, difference in total translation of 1 mm (95% confidence interval -4.7 to 2.9) in favour of the TSP group. In line with the migration data, no significant differences in clinical outcomes were found. Conclusion. The TSP did not influence the course of healing or postoperative fracture motion compared to SHS alone. Based on our results, routine use of the TSP in AO/OTA 31-A2 trochanteric fractures cannot be recommended. The TSP has been shown, in biomechanical studies, to increase stability in sliding hip screw constructs in both unstable and intermediate stable trochanteric fractures, but the clinical evidence is limited. This study showed no advantage of the TSP in unstable (AO 31-A2) fractures in elderly patients when fracture movement was evaluated with radiostereometric analysis. Cite this article: Bone Jt Open 2024;5(1):37–45

Aims. The aim of this study was to compare a bicruciate-retaining (BCR) total knee arthroplasty (TKA) with a posterior cruciate-retaining (CR) TKA design in terms of kinematics, measured using fluoroscopy and stability as micromotion using radiostereometric analysis (RSA). Methods. A total of 40 patients with end-stage osteoarthritis were included in this randomized controlled trial. All patients performed a step-up and lunge task in front of a monoplane fluoroscope one year postoperatively. Femorotibial contact point (CP) locations were determined at every flexion angle and compared between the groups. RSA images were taken at baseline, six weeks, three, six, 12, and 24 months postoperatively. Clinical and functional outcomes were compared postoperatively for two years. Results. The BCR-TKA demonstrated a kinematic pattern comparable to the natural knee’s screw-home mechanism in the step-up task. In the lunge task, the medial CP of the BCR-TKA was more anterior in the early flexion phase, while laterally the CP was more posterior during the entire movement cycle. The BCR-TKA group showed higher tibial migration. No differences were found for the clinical and functional outcomes. Conclusion. The BCR-TKA shows a different kinematic pattern in early flexion/late extension compared to the CR-TKA. The difference between both implants is mostly visible in the flexion phase in which the anterior cruciate ligament is effective; however, both designs fail to fully replicate the motion of a natural knee. The higher migration of the BCR-TKA was concerning and highlights the importance of longer follow-up. Cite this article: Bone Joint J 2023;105-B(1):35–46

Aims. To verify whether secretory leucocyte protease inhibitor (SLPI) can promote early tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction. Methods. In vitro: the mobility of the rat bone mesenchymal stem cells (BMSCs) treated with SLPI was evaluated by scratch assay. Then the expression levels of osteogenic differentiation-related genes were analyzed by real-time quantitative PCR (qPCR) to determine the osteogenic effect of SLPI on BMSCs. In vivo: a rat model of ACL reconstruction was used to verify the effect of SLPI on tendon-to-bone healing. All the animals of the SLPI group and the negative control (NC) group were euthanized for histological evaluation, micro-CT scanning, and biomechanical testing. Results. SLPI improved the migration ability of BMSCs and upregulated the expression of genes related to osteogenic differentiation of BMSCs in vitro. In vivo, the SLPI group had higher histological scores at the tendon-bone interface by histological evaluation. Micro-CT showed more new bone formation and bone ingrowth around the grafted tendon in the SLPI group. Evaluation of the healing strength of the tendon-bone connection showed that the SLPI group had a higher maximum failure force and stiffness. Conclusion. SLPI can effectively promote early tendon-to-bone healing after ACL reconstruction via enhancing the migration and osteogenic differentiation of BMSCs. Cite this article: Bone Joint Res 2022;11(7):503–512

Aims. Femoral bone preparation using compaction technique has been shown to preserve bone and improve implant fixation in animal models. No long-term clinical outcomes are available. There are no significant long-term differences between compaction and broaching techniques for primary total hip arthroplasty (THA) in terms of migration, clinical, and radiological outcomes. Methods. A total of 28 patients received one-stage bilateral primary THA with cementless femoral stems (56 hips). They were randomized to compaction on one femur and broaching on the contralateral femur. Overall, 13 patients were lost to the ten-year follow-up leaving 30 hips to be evaluated in terms of stem migration (using radiostereometry), radiological changes, Harris Hip Score, Oxford Hip Score, and complications. Results. Over a mean follow-up period of 10.6 years, the mean stem subsidence was similar between groups, with a mean of -1.20 mm (95% confidence interval (CI) -2.28 to -0.12) in the broaching group and a mean of -0.73 mm (95% CI -1.65 to 0.20) in the compaction group (p = 0.07). The long-term migration patterns of all stems were similar. The clinical and radiological outcomes were similar between groups. There were two intraoperative fractures in the compaction group that were fixed with cable wire and healed without complications. No stems were revised. Conclusion. Similar stem subsidence and radiological and clinical outcomes were identified after the use of compaction and broaching techniques of the femur at long-term follow-up. Only the compaction group had intraoperative periprosthetic femur fractures, but there were no long-term consequences of these. Cite this article: Bone Jt Open 2021;2(12):1035–1042

Aims. Micromotion of the polyethylene (PE) inlay may contribute to backside PE wear in addition to articulate wear of total knee arthroplasty (TKA). Using radiostereometric analysis (RSA) with tantalum beads in the PE inlay, we evaluated PE micromotion and its relationship to PE wear. Methods. A total of 23 patients with a mean age of 83 years (77 to 91), were available from a RSA study on cemented TKA with Maxim tibial components (Zimmer Biomet). PE inlay migration, PE wear, tibial component migration, and the anatomical knee axis were evaluated on weightbearing stereoradiographs. PE inlay wear was measured as the deepest penetration of the femoral component into the PE inlay. Results. At mean six years’ follow-up, the PE wear rate was 0.08 mm/year (95% confidence interval 0.06 to 0.09 mm/year). PE inlay external rotation was below the precision limit and did not influence PE wear. Varus knee alignment did not influence PE wear (p = 0.874), but increased tibial component total translation (p = 0.041). Conclusion. The PE inlay was well fixed and there was no relationship between PE stability and PE wear. The PE wear rate was low and similar in the medial and lateral compartments. Varus knee alignment did not influence PE wear. Cite this article: Bone Joint Res 2024;13(5):226–236

Aims. Meniscal injuries are common and often induce knee pain requiring surgical intervention. To develop effective strategies for meniscus regeneration, we hypothesized that a minced meniscus embedded in an atelocollagen gel, a firm gel-like material, may enhance meniscus regeneration through cell migration and proliferation in the gel. Hence, the objective of this study was to investigate cell migration and proliferation in atelocollagen gels seeded with autologous meniscus fragments in vitro and examine the therapeutic potential of this combination in an in vivo rabbit model of massive meniscus defect. Methods. A total of 34 Japanese white rabbits (divided into defect and atelocollagen groups) were used to produce the massive meniscus defect model through a medial patellar approach. Cell migration and proliferation were evaluated using immunohistochemistry. Furthermore, histological evaluation of the sections was performed, and a modified Pauli’s scoring system was used for the quantitative evaluation of the regenerated meniscus. Results. In vitro immunohistochemistry revealed that the meniscus cells migrated from the minced meniscus and proliferated in the gel. Furthermore, histological analysis suggested that the minced meniscus embedded in the atelocollagen gel produced tissue resembling the native meniscus in vivo. The minced meniscus group also had a higher Pauli’s score compared to the defect and atelocollagen groups. Conclusion. Our data show that cells in minced meniscus can proliferate, and that implantation of the minced meniscus within atelocollagen induces meniscus regeneration, thus suggesting a novel therapeutic alternative for meniscus tears. Cite this article: Bone Joint Res 2021;10(4):269–276

Aims. The effects of remnant preservation on the anterior cruciate ligament (ACL) and its relationship with the tendon graft remain unclear. We hypothesized that the co-culture of remnant cells and bone marrow stromal cells (BMSCs) decreases apoptosis and enhances the activity of the hamstring tendons and tenocytes, thus aiding ACL reconstruction. Methods. The ACL remnant, bone marrow, and hamstring tendons were surgically harvested from rabbits. The apoptosis rate, cell proliferation, and expression of types I and III collagen, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), and tenogenic genes (scleraxis (SCX), tenascin C (TNC), and tenomodulin (TNMD)) of the hamstring tendons were compared between the co-culture medium (ACL remnant cells (ACLRCs) and BMSCs co-culture) and control medium (BMSCs-only culture). We also evaluated the apoptosis, cell proliferation, migration, and gene expression of hamstring tenocytes with exposure to co-culture and control media. Results. Compared to BMSCs-only culture medium, the co-culture medium showed substantially decreased early and late apoptosis rates, attenuation of intrinsic and extrinsic apoptotic pathways, and enhanced proliferation of the hamstring tendons and tenocytes. In addition, the expression of collagen synthesis, TGF-β, VEGF, and tenogenic genes in the hamstring tendons and tenocytes significantly increased in the co-culture medium compared to that in the control medium. Conclusion. In the presence of ACLRCs and BMSCs, the hamstring tendons and tenocytes significantly attenuated apoptosis and enhanced the expression of collagen synthesis, TGF-β, VEGF, and tenogenic genes. This in vitro study suggests that the ACLRCs mixed with BMSCs could aid regeneration of the hamstring tendon graft during ACL reconstruction. Cite this article: Bone Joint Res 2023;12(1):9–21

Aims. A novel enhanced cement fixation (EF) tibial implant with deeper cement pockets and a more roughened bonding surface was released to market for an existing total knee arthroplasty (TKA) system.This randomized controlled trial assessed fixation of the both the EF (ATTUNE S+) and standard (Std; ATTUNE S) using radiostereometric analysis. Methods. Overall, 50 subjects were randomized (21 EF-TKA and 23 Std-TKA in the final analysis), and had follow-up visits at six weeks, and six, 12, and 24 months to assess migration of the tibial component. Low viscosity bone cement with tobramycin was used in a standardized fashion for all subjects. Patient-reported outcome measure data was captured at preoperative and all postoperative visits. Results. The patient cohort mean age was 66 years (SD seven years), 59% were female, and the mean BMI was 32 kg/m. 2. (SD 6 kg/m. 2. ). Mean two-year subsidence of the EF-TKA was 0.056 mm (95% confidence interval (CI) 0.025 to 0.086) versus 0.006 mm (95% CI -0.029 to 0.040) for the Std-TKA, and the two-year maximum total point motion (MTPM) was 0.285 mm (95% upper confidence limit (UCL) ≤ 0.363) versus 0.346 mm (95% UCL ≤ 0.432), respectively, for a mean difference of -0.061 mm (95% CI -0.196 to 0.074). Inducible displacement also did not differ between groups. The MTPMs between 12 and 24 months for each group was below the published threshold of 0.2 mm for predicting early aseptic loosening (p < 0.001 and p = 0.001, respectively). Conclusion. Both the enhanced fixation and the standard tibial implant design showed fixation with a predicted low risk of long-term aseptic loosening. Cite this article: Bone Jt Open 2024;5(1):20–27

Aims. Although the Fitmore Hip Stem has been on the market for almost 15 years, it is still not well documented in randomized controlled trials. This study compares the Fitmore stem with the CementLeSs (CLS) in several different clinical and radiological aspects. The hypothesis is that there will be no difference in outcome between stems. Methods. In total, 44 patients with bilateral hip osteoarthritis were recruited from the outpatient clinic at a single tertiary orthopaedic centre. The patients were operated with bilateral one-stage total hip arthroplasty. The most painful hip was randomized to either Fitmore or CLS femoral component; the second hip was operated with the femoral component not used on the first side. Patients were evaluated at three and six months and at one, two, and five years postoperatively with patient-reported outcome measures, radiostereometric analysis, dual-energy X-ray absorptiometry, and conventional radiography. A total of 39 patients attended the follow-up visit at two years (primary outcome) and 35 patients at five years. The primary outcome was which hip the patient considered to have the best function at two years. Results. At two and five years, more patients considered the hip with the CLS femoral component as superior but without a statistically significant difference. There were no differences in clinical outcome, magnitude of femoral component migration, or change of bone mineral density at five years. At three months, the Fitmore femoral component had subsided a median -0.71 mm (interquartile range (IQR) -1.67 to -0.20) and the CLS femoral component -0.70 mm (IQR -1.53 to -0.17; p = 0.742). In both groups the femoral head centre had migrated posteriorly (Fitmore -0.17 mm (IQR -0.98 to -0.04) and CLS -0.23 mm (IQR -0.87 to 0.07; p = 0.936)). After three months neither of the femoral components showed much further migration. During the first postoperative year, one Fitmore femoral component was revised due to aseptic loosening. Conclusion. Up to five years, we found no statistically significant difference in outcomes between the Fitmore and the CLS femoral components. The slightly worse outcomes, including one revised hip because of loosening, speaks against the hypothesis that the Fitmore femoral component should be advantageous compared to the CLS if more patients had been recruited to this study. Cite this article: Bone Jt Open 2023;4(5):306–314

Objectives. Mesenchymal stem cells (MSCs) are of growing interest in terms of bone regeneration. Most preclinical trials utilize bone-marrow-derived mesenchymal stem cells (bMSCs), although this is not without isolation and expansion difficulties. The aim of this study was: to compare the characteristics of bMSCs and adipose-derived mesenchymal stem cells (AdMSCs) from juvenile, adult, and ovarectomized (OVX) rats; and to assess the effect of human parathyroid hormone (hPTH) 1-34 on their osteogenic potential and migration to stromal cell-derived factor-1 (SDF-1). Methods. Cells were isolated from the adipose and bone marrow of juvenile, adult, and previously OVX Wistar rats, and were characterized with flow cytometry, proliferation assays, osteogenic and adipogenic differentiation, and migration to SDF-1. Experiments were repeated with and without intermittent hPTH 1-34. Results. Juvenile and adult MSCs demonstrated significantly increased osteogenic and adipogenic differentiation and superior migration towards SDF-1 compared with OVX groups; this was the case for AdMSCs and bMSCs equally. Parathyroid hormone (PTH) increased parameters of osteogenic differentiation and migration to SDF-1. This was significant for all cell types, although it had the most significant effect on cells derived from OVX animals. bMSCs from all groups showed increased mineralization and migration to SDF-1 compared with AdMSCs. Conclusion. Juvenile MSCs showed significantly greater migration to SDF-1 and significantly greater osteogenic and adipogenic differentiation compared with cells from osteopenic rats; this was true for bMSCs and AdMSCs. The addition of PTH increased these characteristics, with the most significant effect on cells derived from OVX animals, further illustrating possible clinical application of both PTH and MSCs in bone regenerative therapies. Cite this article:L. Osagie-Clouard, A. Sanghani-Kerai, M. Coathup, R. Meeson, T. Briggs, G. Blunn. The influence of parathyroid hormone 1-34 on the osteogenic characteristics of adipose- and bone-marrow-derived mesenchymal stem cells from juvenile and ovarectomized rats. Bone Joint Res 2019;8:397–404. DOI: 10.1302/2046-3758.88.BJR-2019-0018.R1

Aims. Rheumatoid arthritis (RA), which mainly results from fibroblast-like synoviocyte (FLS) dysfunction, is related to oxidative stress. Advanced oxidation protein products (AOPPs), which are proinflammatory mediators and a novel biomarker of oxidative stress, have been observed to accumulate significantly in the serum of RA patients. Here, we present the first investigation of the effects of AOPPs on RA-FLSs and the signalling pathway involved in AOPP-induced inflammatory responses and invasive behaviour. Methods. We used different concentrations of AOPPs (50 to 200 µg/ml) to treat RA-FLSs. Cell migration and invasion and the expression levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and MMP-13 were investigated. Western blot and immunofluorescence were used to analyze nuclear factor-κB (NF-κB) activation. Results. AOPPs promoted RA-FLS migration and invasion in vitro and significantly induced the messenger RNA (mRNA) and protein expression of TNF-α, IL-6, MMP-3, and MMP-13 in dose- and time-dependent manners. Moreover, AOPPs markedly activated the phosphorylation of nuclear factor-κB (NF-κB) p65 protein, which triggered inhibitory kappa B-alpha (IκBα) degradation, NF-κB p65 protein phosphorylation, and NF-κB p65 translocation into the nucleus. Furthermore, treatment with a neutralizing antibody specific to receptor for advanced glycation end products (RAGE) significantly suppressed aggressive behaviour and inflammation, decreased TNF-α, IL-6, MMP-3, and MMP-13 expression, and blocked AOPP-induced NF-κB pathway activation. Conclusion. The results indicate that AOPPs can enhance aggressive behaviour and the inflammatory response in RA-FLSs via the RAGE–NF-κB pathway. These results present AOPPs as a new class of potentially important mediators of progressive disease in RA patients. Cite this article: Bone Joint Res 2021;10(4):259–268

Aims. This study aimed, through bioinformatics analysis, to identify the potential diagnostic markers of osteoarthritis, and analyze the role of immune infiltration in synovial tissue. Methods. The gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by R software. Functional enrichment analyses were performed and protein-protein interaction networks (PPI) were constructed. Then the hub genes were screened. Biomarkers with high value for the diagnosis of early osteoarthritis (OA) were validated by GEO datasets. Finally, the CIBERSORT algorithm was used to evaluate the immune infiltration between early-stage OA and end-stage OA, and the correlation between the diagnostic marker and infiltrating immune cells was analyzed. Results. A total of 88 DEGs were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that DEGs were significantly enriched in leucocyte migration and interleukin (IL)-17 signalling pathways. Disease ontology (DO) indicated that DEGs were mostly enriched in rheumatoid arthritis. Six hub genes including FosB proto-oncogene, AP-1 transcription factor subunit (FOSB); C-X-C motif chemokine ligand 2 (CXCL2); CXCL8; IL-6; Jun proto-oncogene, AP-1 transcription factor subunit (JUN); and Activating transcription factor 3 (ATF3) were identified and verified by GEO datasets. ATF3 (area under the curve = 0.975) turned out to be a potential biomarker for the diagnosis of early OA. Several infiltrating immune cells varied significantly between early-stage OA and end-stage OA, such as resting NK cells (p = 0.016), resting dendritic cells (p = 0.043), and plasma cells (p = 0.043). Additionally, ATF3 was significantly correlated with resting NK cells (p = 0.034), resting dendritic cells (p = 0.026), and regulatory T cells (Tregs, p = 0.018). Conclusion. ATF3 may be a potential diagnostic marker for early diagnosis and treatment of OA, and immune cell infiltration provides new perspectives for understanding the mechanism during OA progression. Cite this article: Bone Joint Res 2022;11(9):679–689

Objectives. Our primary aim was to describe migration of the Exeter stem with a 32 mm head on highly crosslinked polyethylene and whether this is influenced by age. Our secondary aims were to assess functional outcome, satisfaction, activity, and bone mineral density (BMD) according to age. Patients and Methods. A prospective cohort study was conducted. Patients were recruited into three age groups: less than 65 years (n = 65), 65 to 74 years (n = 68), and 75 years and older (n = 67). There were 200 patients enrolled in the study, of whom 115 were female and 85 were male, with a mean age of 69.9 years (sd 9.5, 42 to 92). They were assessed preoperatively, and at three, 12 and, 24 months postoperatively. Stem migration was assessed using Einzel-Bild-Röntgen-Analyse (EBRA). Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Harris Hip Score (HHS), Hip Disability and Osteoarthritis Outcome Score (HOOS), EuroQol-5 domains questionnaire (EQ-5D), short form-36 questionnaire (SF-36,) and patient satisfaction were used to assess outcome. The Lower Extremity Activity Scale (LEAS), Timed Up and Go (TUG) test, and activPAL monitor (energy expelled, time lying/standing/walking and step count) were used to assess activity. The BMD was assessed in Gruen and Charnley zones. Results. Mean varus/valgus tilt was -0.77⁰ and axial subsidence was -1.20 mm. No significant difference was observed between age groups (p ⩾ 0.07). There was no difference according to age group for postoperative WOMAC (p ⩾ 0.11), HHS (p ⩾ 0.06), HOOS (p ⩾ 0.46), EQ-5D (p ⩾ 0.38), patient satisfaction (p ⩾ 0.05), or activPAL (p ⩾ 0.06). Patients 75 years and older had a worse SF-36 physical function (p = 0.01) and physical role (p = 0.03), LEAS score (p < 0.001), a shorter TUG (p = 0.01), and a lower BMD in Charnley zone 1 (p = 0.02). Conclusion. Exeter stem migration is within normal limits and is not influenced by age group. Functional outcome, patient satisfaction, activity level, and periprosthetic BMD are similar across all age groups. Cite this article: N. D. Clement, M. Bardgett, K. Merrie, S. Furtado, R. Bowman, D. J. Langton, D. J. Deehan, J. Holland. Cemented Exeter total hip arthroplasty with a 32 mm head on highly crosslinked polyethylene: Does age influence functional outcome, satisfaction, activity, stem migration, and periprosthetic bone mineral density? Bone Joint Res 2019;8:275–287. DOI: 10.1302/2046-3758.86.BJR-2018-0300.R1

Transforming growth factor-beta2 (TGF-β2) is recognized as a versatile cytokine that plays a vital role in regulation of joint development, homeostasis, and diseases, but its role as a biological mechanism is understood far less than that of its counterpart, TGF-β1. Cartilage as a load-resisting structure in vertebrates however displays a fragile performance when any tissue disturbance occurs, due to its lack of blood vessels, nerves, and lymphatics. Recent reports have indicated that TGF-β2 is involved in the physiological processes of chondrocytes such as proliferation, differentiation, migration, and apoptosis, and the pathological progress of cartilage such as osteoarthritis (OA) and rheumatoid arthritis (RA). TGF-β2 also shows its potent capacity in the repair of cartilage defects by recruiting autologous mesenchymal stem cells and promoting secretion of other growth factor clusters. In addition, some pioneering studies have already considered it as a potential target in the treatment of OA and RA. This article aims to summarize the current progress of TGF-β2 in cartilage development and diseases, which might provide new cues for remodelling of cartilage defect and intervention of cartilage diseases

Aims. The Mathys Affinis Short is the most frequently used stemless total shoulder prosthesis in the UK. The purpose of this prospective cohort study is to report the survivorship, clinical, and radiological outcomes of the first independent series of the Affinis Short prosthesis. Methods. From January 2011 to January 2019, a total of 141 Affinis Short prostheses were implanted in 127 patients by a single surgeon. Mean age at time of surgery was 68 (44 to 89). Minimum one year and maximum eight year follow-up (mean 3.7 years) was analyzed using the Oxford Shoulder Score (OSS) at latest follow-up. Kaplan-Meier survivorship analysis was performed with implant revision as the endpoint. Most recently performed radiographs were reviewed for component radiolucent lines (RLLs) and proximal humeral migration. Results. Five shoulders underwent revision surgery (3.5%); three for rotator cuff failure, one for infection, and one for component malposition. Survivorship of the implant was 95.4% (95% confidence interval 90.1% to 97.9%) at five and nine years. Mean OSS improved significantly compared to preoperative values from 19.0 (1 to 35) to 43.3 (7 to 48) (p < 0.001). Radiological analysis was undertaken for 99 shoulders. This revealed humeral RLLs in one case (1%), glenoid RLLs in 15 cases (15.2%), and radiological rotator cuff failure in 22 cases (22.2%). Conclusion. This prospective cohort study shows encouraging short- to mid-term survivorship and clinical and radiological results for the Mathys Affinis Short, Short Stem Total Shoulder Prosthesis. Level of Evidence: IV. Cite this article: Bone Jt Open 2021;2(1):58–65

Aims. Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway. Methods. A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses. Results. GNAQ-knockdown showed down-regulation of tumour growth through mitogen-activated protein kinase (MAPK) signalling in lung cancer cells, but not increased apoptosis. We found that GNAQ-knockdown induced EMT and promoted invasiveness. GNAQ-knockdown cells injected into the bone marrow of murine tibia induced tumour growth and bone-to-lung metastasis, whereas it did not in control mice. Moreover, the knockdown of GNAQ enhanced cancer stem cell-like properties in lung cancer cells, which resulted in the development of resistance to chemotherapy. Conclusion. The present study reveals that the GNAQ-knockdown induced cancer stem cell-like properties. Cite this article: Bone Joint Res 2021;10(5):310–320

Aims. Total hip arthroplasty (THA) in patients with post-polio residual paralysis (PPRP) is challenging. Despite relief in pain after THA, pre-existing muscle imbalance and altered gait may cause persistence of difficulty in walking. The associated soft tissue contractures not only imbalances the pelvis, but also poses the risk of dislocation, accelerated polyethylene liner wear, and early loosening. Methods. In all, ten hips in ten patients with PPRP with fixed pelvic obliquity who underwent THA as per an algorithmic approach in two centres from January 2014 to March 2018 were followed-up for a minimum of two years (2 to 6). All patients required one or more additional soft tissue procedures in a pre-determined sequence to correct the pelvic obliquity. All were invited for the latest clinical and radiological assessment. Results. The mean Harris Hip Score at the latest follow-up was 79.2 (68 to 90). There was significant improvement in the coronal pelvic obliquity from 16.6. o. (SD 7.9. o. ) to 1.8. o. (SD 2.4. o. ; p < 0.001). Radiographs of all ten hips showed stable prostheses with no signs of loosening or migration, regardless of whether paralytic or non-paralytic hip was replaced. No complications, including dislocation or infection related to the surgery, were observed in any patient. The subtrochanteric shortening osteotomy done in two patients had united by nine months. Conclusion. Simultaneous correction of soft tissue contractures is necessary for obtaining a stable hip with balanced pelvis while treating hip arthritis by THA in patients with PPRP and fixed pelvic obliquity. Cite this article: Bone Jt Open 2021;2(9):696–704

Objectives. The aim of this study was to investigate the role of miR-126 in the development of osteoarthritis, as well as the potential molecular mechanisms involved, in order to provide a theoretical basis for osteoarthritis treatment and a novel perspective for clinical therapy. Methods. Human chondrocyte cell line CHON-001 was administrated by different doses of interleukin (IL)-1β to simulate inflammation. Cell viability, migration, apoptosis, IL-6, IL-8, and tumour necrosis factor (TNF)-α expression, as well as expression of apoptosis-related factors, were measured to assess inflammation. miR-126 expression was measured by quantitative polymerase chain reaction (qPCR). Cells were then transfected with miR-126 inhibitor to assess the effect of miR-126 on IL-1β-injured CHON-001 cells. Expression of B-cell lymphoma 2 (Bcl-2) and the activity of mitogen-activated protein kinase (MAPK) / Jun N-terminal kinase (JNK) signaling pathway were measured by Western blot to explore the underlying mechanism through which miR-126 affects IL-1β-induced inflammation. Results. After IL-1β administration, cell viability and migration were suppressed while apoptosis was enhanced. Expression of IL-6, IL-8, and TNF-α were all increased, and miR-126 was upregulated. In IL-1β-administrated CHON-001 cells, miR-126 inhibitor suppressed the effect of IL-1β on cell viability, migration, apoptosis, and inflammatory response. Bcl-2 expression was negatively regulated with miR-126 in IL-1β-administrated cells, and thus affected expressions of phosphorylated MAPK and JNK. Conclusion. IL-1β-induced inflammatory markers and miR-126 was upregulated. Inhibition of miR-126 decreased IL-1β-induced inflammation and cell apoptosis, and upregulated Bcl-2 expression via inactivating the MAKP/JNK signalling pathway. Cite this article: C. D. Yu, W. H. Miao, Y. Y. Zhang, M. J. Zou, X. F. Yan. Inhibition of miR-126 protects chondrocytes from IL-1β induced inflammation via upregulation of Bcl-2. Bone Joint Res 2018;7:414–421. DOI: 10.1302/2046-3758.76.BJR-2017-0138.R1

Aims. Hip displacement, common in patients with cerebral palsy (CP), causes pain and hinders adequate care. Hip reconstructive surgery (HRS) is performed to treat hip displacement; however, only a few studies have quantitatively assessed femoral head sphericity after HRS. The aim of this study was to quantitatively assess improvement in hip sphericity after HRS in patients with CP. Methods. We retrospectively analyzed hip radiographs of patients who had undergone HRS because of CP-associated hip displacement. The pre- and postoperative migration percentage (MP), femoral neck-shaft angle (NSA), and sphericity, as determined by the Mose hip ratio (MHR), age at surgery, Gross Motor Function Classification System level, surgical history including Dega pelvic osteotomy, and triradiate cartilage status were studied. Regression analyses using linear mixed model were performed to identify factors affecting hip sphericity improvement. Results. A total of 108 patients were enrolled. The mean preoperative MP was 58.3% (SD 31.7%), which improved to 9.1% (SD 15.6%) at the last follow-up. NSA and MHR improved from 156.5° (SD 11.5°) and 82.3% (SD 8.6%) to 126.0° (SD 18.5°) and 89.1% (SD 9.0%), respectively. Factors affecting the postoperative MHR were preoperative MP (p = 0.005), immediate postoperative MP (p = 0.032), and history of Dega osteotomy (p = 0.046). Conclusion. We found that hip sphericity improves with HRS. Preoperative MP, reduction quality, and acetabular coverage influence femoral head remodelling. We recommend that surgeons should consider intervention early before hip displacement progresses and that during HRS, definite reduction and coverage of the femoral head should be obtained. Cite this article: Bone Joint J 2021;103-B(1):198–203

Aims. To compare the in vivo long-term fixation achieved by two acetabular components with different porous ingrowth surfaces using radiostereometric analysis (RSA). Methods. This was a minimum ten-year follow-up of a prospective randomized trial of 62 hips with two different porous ingrowth acetabular components. RSA exams had previously been acquired through two years of follow-up. Patients returned for RSA examination at a minimum of ten years. In addition, radiological appearance of these acetabular components was analyzed, and patient-reported outcome measures (PROMs) obtained. Results. In all, 15 hips were available at ten years. There was no statistically significant difference in PROMS between the two groups; PROMs were improved at ten years compared to preoperative scores. Conventional radiological assessment revealed well-fixed components. There was minimal movement for both porous surfaces in translation (X, Y, Z, 3D translation in mm (median and interquartile range (IQR)), StikTite (Smith and Nephew, Memphis, Tennessee, USA): 0.03 (1.08), 0.12 (0.7), 0.003 (2.3), 0.37 (0.30), and Roughcoat (Smith and Nephew): -0.6 (0.59),–0.1 (0.49), 0.1 (1.12), 0.48 (0.38)), and rotation (X, Y, Z rotation in degrees (median and IQR), (Stiktite: -0.4 (3), 0.28 (2), -0.2 (1), and Roughcoat: - 0.4 (1),–0.1 (1), 0.2 (2)). There was no statistically significant difference between the two cohorts (p-value for X, Y, Z, 3D translation - 0.54, 0.46, 0.87, 0.55 and for X, Y, Z rotation - 0.41, 0.23, 0.23 respectively) at ten years. There was significant correlation between two years and ten years 3D translation for all components (r = 0.81(p =< 0.001)). Conclusion. Both porous ingrowth surfaces demonstrated excellent fixation on plain radiographs and with RSA at ten years. Short-term RSA data are good predictors for long-term migration data

Aims. In elderly patients with osteoarthritis and protrusio who require arthroplasty, dislocation of the hip is difficult due to migration of the femoral head. Traditionally, neck osteotomy is performed in situ, so this is not always achieved. Therefore, the purpose of this study is to describe a partial resection of the posterior wall in severe protrusio. Methods. This is a descriptive observational study, which describes the surgical technique of the partial resection of the posterior wall during hip arthroplasty in patients with severe acetabular protrusio operated on between January 2007 and February 2017. Results. In all, 49 hip arthroplasties were performed. The average age of patients was 60 years, and idiopathic was the most frequent aetiology of protrusio. All patients were treated with femoral head autograft and no intra- or postoperative complications were reported. No patients required revision surgery. Conclusion. Partial resection of the posterior wall demonstrated to be a safe surgical technique with 100% survival in a follow-up to ten years in total hip arthroplasty due to severe acetabular protrusio. Cite this article: Bone Joint Open 2020;1-7:431–437

Aims. Complex total hip arthroplasty (THA) with subtrochanteric shortening osteotomy is necessary in conditions other than developmental dysplasia of the hip (DDH) and septic arthritis sequelae with significant proximal femur migration. Our aim was to evaluate the hip centre restoration with THAs in these hips. Methods. In all, 27 THAs in 25 patients requiring THA with femoral shortening between 2012 and 2019 were assessed. Bilateral shortening was required in two patients. Subtrochanteric shortening was required in 14 out of 27 hips (51.9%) with aetiology other than DDH or septic arthritis. Vertical centre of rotation (VCOR), horizontal centre of rotation, offset, and functional outcome was calculated. The mean followup was 24.4 months (5 to 92 months). Results. The mean VCOR was 17.43 mm (9.5 to 27 mm) and horizontal centre of rotation (HCOR) was 24.79 mm (17.2 to 37.6 mm). Dislocation at three months following acetabulum reconstruction required femoral shortening for offset correction and hip centre restoration in one hip. Mean horizontal offset was 39.72 (32.7 to 48.2 mm) compared to 42.89 (26.7 to 50.6 mm) on the normal side. Mean Harris Hip Score (HHS) of 22.64 (14 to 35) improved to 79.43 (68 to 92). Mean pre-operative shortening was 3.95 cm (2 to 8 cm). Residual limb length discrepancy was 1.5 cm (0 to 2 cm). Sciatic neuropraxia in two patients recovered by six months, and femoral neuropraxia in one hip recovered by 12 months. Mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was 13.92 (9 to 19). Mean 12-item short form survey (SF-12) physical scores of 50.6 and mental of 60.12 were obtained. Conclusion. THA with subtrochanteric shortening is valuable in complex hips with high dislocation. The restoration of the hip centre of rotation and offset is important in these hips. Level of evidence IV. Femoral shortening useful in conditions other than DDH and septic sequelae. Restoration of hip centre combined with offset to be planned and ensured

Objectives. Osteophytes are products of active endochondral and intramembranous ossification, and therefore could theoretically provide significant efficacy as bone grafts. In this study, we compared the bone mineralisation effectiveness of osteophytes and cancellous bone, including their effects on secretion of growth factors and anabolic effects on osteoblasts. Methods. Osteophytes and cancellous bone obtained from human patients were transplanted onto the calvaria of severe combined immunodeficient mice, with Calcein administered intra-peritoneally for fluorescent labelling of bone mineralisation. Conditioned media were prepared using osteophytes and cancellous bone, and growth factor concentration and effects of each graft on proliferation, differentiation and migration of osteoblastic cells were assessed using enzyme-linked immunosorbent assays, MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)) assays, quantitative real-time polymerase chain reaction, and migration assays. Results. After six weeks, the area of mineralisation was significantly higher for the transplanted osteophytes than for the cancellous bone (43803 μm. 2. , . sd. 14660 versus 9421 μm. 2. , . sd. 5032, p = 0.0184, one-way analysis of variance). Compared with cancellous bone, the conditioned medium prepared using osteophytes contained a significantly higher amounts of transforming growth factor (TGF)-β1 (471 pg/ml versus 333 pg/ml, p = 0.0001, Wilcoxon rank sum test), bone morphogenetic protein (BMP)-2 (47.75 pg/ml versus 32 pg/ml, p = 0.0214, Wilcoxon rank sum test) and insulin-like growth factor (IGF)-1 (314.5 pg/ml versus 191 pg/ml, p = 0.0418, Wilcoxon rank sum test). The stronger effects of osteophytes towards osteoblasts in terms of a higher proliferation rate, upregulation of gene expression of differentiation markers such as alpha-1 type-1 collagen and alkaline phosphate, and higher migration, compared with cancellous bone, was confirmed. Conclusion. We provide evidence of favourable features of osteophytes for bone mineralisation through a direct effect on osteoblasts. The acceleration in metabolic activity of the osteophyte provides justification for future studies evaluating the clinical use of osteophytes as autologous bone grafts. Cite this article: K. Ishihara, K. Okazaki, T. Akiyama, Y. Akasaki, Y. Nakashima. Characterisation of osteophytes as an autologous bone graft source: An experimental study in vivo and in vitro. Bone Joint Res 2017;6:73–81. DOI: 10.1302/2046-3758.62.BJR-2016-0199.R1

Aims. The diversity of femoral morphology renders femoral component sizing in total hip arthroplasty (THA) challenging. We aimed to determine whether femoral morphology and femoral component filling influence early clinical and radiological outcomes following THA using fully hydroxyapatite (HA)-coated femoral components. Methods. We retrospectively reviewed records of 183 primary uncemented THAs. Femoral morphology, including Dorr classification, canal bone ratio (CBR), canal flare index (CFI), and canal-calcar ratio (CCR), were calculated on preoperative radiographs. The canal fill ratio (CFR) was calculated at different levels relative to the lesser trochanter (LT) using immediate postoperative radiographs: P1, 2 cm above LT; P2, at LT; P3, 2 cm below LT; and D1, 7 cm below LT. At two years, radiological femoral component osseointegration was evaluated using the Engh score, and hip function using the Postel Merle d’Aubigné (PMA) and Oxford Hip Score (OHS). Results. CFR was moderately correlated with CCR at P1 (r = 0.44; p < 0.001), P2 (r = 0.53; p < 0.001), and CFI at P1 (r = − 0.56; p < 0.001). Absence of spot welds (n = 3, 2%) was associated with lower CCR (p = 0.049), greater CFI (p = 0.017), and lower CFR at P3 (p = 0.015). Migration (n = 9, 7%) was associated with lower CFR at P2 (p = 0.028) and P3 (p = 0.007). Varus malalignment (n = 7, 5%), predominantly in Dorr A femurs (p = 0.028), was associated with lower CFR at all levels (p < 0.05). Absence of spot welds was associated with lower PMA gait (p = 0.012) and migration with worse OHS (p = 0.032). Conclusion. This study revealed that femurs with insufficient proximal filling tend to have less favourable radiological outcomes following uncemented THA using a fully HA-coated double-tapered femoral component. Cite this article: Bone Joint Res. 2020;9(4):182–191

Objectives. Re-rupture is common after primary flexor tendon repair. Characterization of the biological changes in the ruptured tendon stumps would be helpful, not only to understand the biological responses to the failed tendon repair, but also to investigate if the tendon stumps could be used as a recycling biomaterial for tendon regeneration in the secondary grafting surgery. Methods. A canine flexor tendon repair and failure model was used. Following six weeks of repair failure, the tendon stumps were analyzed and characterized as isolated tendon-derived stem cells (TDSCs). Results. Failed-repair stump tissue showed cellular accumulation of crumpled and disoriented collagen fibres. Compared with normal tendon, stump tissue had significantly higher gene expression of collagens I and III, matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and insulin-like growth factor (IGF). The stump TDSCs presented both mesenchymal stem and haematopoietic cell markers with significantly increased expression of CD34, CD44, and CD90 markers. Stump TDSCs exhibited similar migration but a lower proliferation rate, as well as similar osteogenic differentiation but a lower chondrogenic/adipogenic differentiation capability, compared with normal TDSCs. Stump TDSCs also showed increasing levels of SRY-box 2 (Sox2), octamer-binding transcription factor 4 (Oct4), tenomodulin (TNMD), and scleraxis (Scx) protein and gene expression. Conclusion. We found that a failed repair stump had increased cellularity that preserved both mesenchymal and haematopoietic stem cell characteristics, with higher collagen synthesis, MMP, and growth factor gene expression. This study provides evidence that tendon stump tissue has regenerative potential. Cite this article: C-C. Lu, T. Zhang, R. L. Reisdorf, P. C. Amadio, K-N. An, S. L. Moran, A. Gingery, C. Zhao. Biological analysis of flexor tendon repair-failure stump tissue: A potential recycling of tissue for tendon regeneration. Bone Joint Res 2019;8:232–245. DOI: 10.1302/2046-3758.86.BJR-2018-0239.R1

Aims

Instability is a common cause of failure after total hip arthroplasty. A novel reverse total hip has been developed, with a femoral cup and acetabular ball, creating enhanced mechanical stability. The purpose of this study was to assess the implant fixation using radiostereometric analysis (RSA), and the clinical safety and efficacy of this novel design.

Objectives. Venous thromboembolism (VTE) is a major potential complication following orthopaedic surgery. Subcutaneously administered enoxaparin has been used as the benchmark to reduce the incidence of VTE. However, concerns have been raised regarding the long-term administration of enoxaparin and its possible negative effects on bone healing and bone density with an increase of the risk of osteoporotic fractures. New oral anticoagulants such as rivaroxaban have recently been introduced, however, there is a lack of information regarding how these drugs affect bone metabolism and post-operative bone healing. Methods. We measured the migration and proliferation capacity of mesenchymal stem cells (MSCs) under enoxaparin or rivaroxaban treatment for three consecutive weeks, and evaluated effects on MSC mRNA expression of markers for stress and osteogenic differentiation. Results. We demonstrate that enoxaparin, but not rivaroxaban, increases the migration potential of MSCs and increases their cell count in line with elevated mRNA expression of C-X-C chemokine receptor type 4 (CXCR4), tumor necrosis factor alpha (TNFα), and alpha-B-crystallin (CryaB). However, a decrease in early osteogenic markers (insulin-like growth factors 1 and 2 (IGF1, IGF2), bone morphogenetic protein2 (BMP2)) indicated inhibitory effects on MSC differentiation into osteoblasts caused by enoxaparin, but not by rivaroxaban. Conclusions. Our findings may explain the adverse effects of enoxaparin treatment on bone healing. Rivaroxaban has no significant impact on MSC metabolism or capacity for osteogenic differentiation in vitro. Cite this article: Dr H. Pilge. Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing. Bone Joint Res 2016;5:95–100. DOI: 10.1302/2046-3758.53.2000595

Aims

Rheumatoid arthritis (RA) is a common chronic immune disease. Berberine, as its main active ingredient, was also contained in a variety of medicinal plants such as Berberaceae, Buttercup, and Rutaceae, which are widely used in digestive system diseases in traditional Chinese medicine with anti-inflammatory and antibacterial effects. The aims of this article were to explore the therapeutic effect and mechanism of berberine on rheumatoid arthritis.

Bone regeneration and repair are crucial to ambulation and quality of life. Factors such as poor general health, serious medical comorbidities, chronic inflammation, and ageing can lead to delayed healing and nonunion of fractures, and persistent bone defects. Bioengineering strategies to heal bone often involve grafting of autologous bone marrow aspirate concentrate (BMAC) or mesenchymal stem cells (MSCs) with biocompatible scaffolds. While BMAC shows promise, variability in its efficacy exists due to discrepancies in MSC concentration and robustness, and immune cell composition. Understanding the mechanisms by which macrophages and lymphocytes – the main cellular components in BMAC – interact with MSCs could suggest novel strategies to enhance bone healing. Macrophages are polarized into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, and influence cell metabolism and tissue regeneration via the secretion of cytokines and other factors. T cells, especially helper T1 (Th1) and Th17, promote inflammation and osteoclastogenesis, whereas Th2 and regulatory T (Treg) cells have anti-inflammatory pro-reconstructive effects, thereby supporting osteogenesis. Crosstalk among macrophages, T cells, and MSCs affects the bone microenvironment and regulates the local immune response. Manipulating the proportion and interactions of these cells presents an opportunity to alter the local regenerative capacity of bone, which potentially could enhance clinical outcomes.

Cite this article: Bone Joint Res 2024;13(9):462–473.

Aims

Pelvic discontinuity is a rare but increasingly common complication of total hip arthroplasty (THA). This single-centre study evaluated the performance of custom-made triflange acetabular components in acetabular reconstruction with pelvic discontinuity by determining: 1) revision and overall implant survival rates; 2) discontinuity healing rate; and 3) Harris Hip Score (HHS).

Aims

Cartilage injuries rarely heal spontaneously and often require surgical intervention, leading to the formation of biomechanically inferior fibrous tissue. This study aimed to evaluate the possible effect of amelogenin on the healing process of a large osteochondral injury (OCI) in a rat model.

Aims

Both the femoral and tibial component are usually cemented at revision total knee arthroplasty (rTKA), while stems can be added with either cemented or press-fit (hybrid) fixation. The aim of this study was to compare the long-term stability of rTKA with cemented and press-fitted stems, using radiostereometric analysis (RSA).

Aims

The primary outcome was investigating differences in wear, as measured by femoral head penetration, between cross-linked vitamin E-diffused polyethylene (vE-PE) and cross-linked polyethylene (XLPE) acetabular component liners and between 32 and 36 mm head sizes at the ten-year follow-up. Secondary outcomes included acetabular component migration and patient-reported outcome measures (PROMs) such as the EuroQol five-dimension questionnaire, 36-Item Short-Form Health Survey, Harris Hip Score, and University of California, Los Angeles Activity Scale (UCLA).

Aims

Our objective was describing an algorithm to identify and prevent vascular injury in patients with intrapelvic components.

Aims

The aim of this study was to assess the clinical and radiological results of patients who were revised using a custom-made triflange acetabular component (CTAC) for component loosening and pelvic discontinuity (PD) after previous total hip arthroplasty (THA).

Aims

Radiostereometric analysis (RSA) is the most accurate radiological method to measure in vivo wear of highly cross-linked polyethylene (XLPE) acetabular components. We have previously reported very low wear rates for a sequentially irradiated and annealed X3 XLPE liner (Stryker Orthopaedics, USA) when used in conjunction with a 32 mm femoral heads at ten-year follow-up. Only two studies have reported the long-term wear rate of X3 liners used in conjunction with larger heads using plain radiographs which have poor sensitivity. The aim of this study was to measure the ten-year wear of thin X3 XLPE liners against larger 36 or 40 mm articulations with RSA.

Aims

The aim of this study was to evaluate the survival of a collarless, straight, hydroxyapatite-coated femoral stem in total hip arthroplasty (THA) at a minimum follow-up of 20 years.