Aims. To examine how eukaryotic translation initiation factor 5A (eIF5A) regulates osteoarthritis (OA) during mechanical overload and the specific mechanism. Methods. Histological experiments used human bone samples and C57BL/6J mice knee samples. All cell experiments were performed using mice primary chondrocytes. Messenger RNA (mRNA) sequencing was performed on chondrocytes treated with 20% cyclic tensile strain for 24 hours. Western blot (WB) and quantitative polymerase chain reaction were employed to detect relevant indicators of cartilage function in chondrocytes. We created the destabilization of the medial meniscus (DMM) model and the mechanical overload-induced OA model and injected with overexpressing eIF5A adenovirus (eIF5A-ADV). Cartilage degeneration was evaluated using Safranin O/Fast Green staining. Relative protein levels were ascertained by immunohistochemistry (IHC) and immunofluorescence (IF) staining. Results. After OA initiation, eIF5A caused an upregulation of type II collagen (COL2) and a downregulation of matrix metalloproteinase 13 (MMP13), P16, and P21, which postponed the aggravation of OA. Further sequencing and experimental findings revealed that eIF5A knockdown accelerated the progression of OA by boosting the expression of histone acetyltransferase cyclic-adenosine monophosphate response element binding protein (CREB)-binding protein (CREBBP) to mediate activation of the Notch pathway. Conclusion. Our findings identified a crucial functional mechanism for the onset of OA, and suggest that intra-articular eIF5A injections might be a useful therapeutic strategy for OA treatment. Cite this article: Bone Joint Res 2025;14(2):124–135

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Fracture-related infections (FRIs) are a major concern for patients and healthcare systems, yet their impact on mental health has been largely overlooked. This study aimed to assess the longitudinal impact of FRI on patients’ quality of life.

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Valgus subsidence of uncemented tibial components following medial unicompartmental knee arthroplasty (UKA) poses a challenge in the early postoperative phase, necessitating a comprehensive understanding of its prevalence, risk factors, and impact on patient outcomes.

Aims. The Bracing Adolescent Idiopathic Scoliosis (BASIS) study is a randomized controlled non-inferiority pragmatic trial of ‘full-time bracing’ (FTB) compared to ‘night-time bracing’ (NTB) for the treatment of adolescent idiopathic scoliosis (AIS). We anticipated that recruiting patients to BASIS would be challenging, as it is a paediatric trial comparing two markedly different bracing pathways. No previous studies have compared the experiences of AIS patients treated with FTB to those treated with NTB. This qualitative study was embedded in BASIS to explore families’ perspectives of BASIS, to inform trial communication, and to identify strategies to support patients treated in a brace. Methods. Semi-structured interviews were conducted with parents (n = 26) and young people (n = 21) who had been invited to participate in BASIS at ten of the 22 UK paediatric spine services in hospitals recruiting to BASIS. Audio-recorded interviews were transcribed and analyzed thematically. Results. Families viewed their interactions with BASIS recruiters positively, but were often confused about core aspects of BASIS, such as the aims, expectations of bracing, and the process of randomization. Participants typically expressed a preference for NTB, but recruiters may have framed NTB more favourably. Patients and parents reported challenges wearing a brace, such as physical discomfort, feelings of self-consciousness, difficulty participating in physical activities, and strain on financial resources to support brace use. Patients in FTB reported more pronounced challenges. While families valued health professional support, they felt there was a lack of social, emotional, and school support, and relied on online resources, as well private counselling services to address this need. Conclusion. The findings informed the development of resources and strategies, including guidance for schools and the recommendations in this paper, to support patients to wear NTB and FTB as prescribed. The results indicated opportunities for recruiters to enhance trial communication in ways that could improve informed consent and recruitment to BASIS, and inform future trials of bracing. Cite this article: Bone Jt Open 2025;6(2):135–146

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Worldwide controversy exists on the optimal treatment of stable dysplastic hips. The most common treatment options are abduction brace treatment and active surveillance. The primary aim of this study was to assess the effect of active surveillance in stable hip dysplasia, by investigating the percentage of Graf IIb stable dysplastic hips that recover spontaneously without abduction brace treatment. The second aim was to identify prognostic factors for spontaneous recovery of stable dysplastic hips.

Aims. The “2 to 10% strain rule” for fracture healing has been widely interpreted to mean that interfragmentary strain greater than 10% predisposes a fracture to nonunion. This interpretation focuses on the gap-closing strain (axial micromotion divided by gap size), ignoring the region around the gap where osteogenesis typically initiates. The aim of this study was to measure gap-closing and 3D interfragmentary strains in plated ovine osteotomies and associate local strain conditions with callus mineralization. Methods. MicroCT scans of eight female sheep with plated mid-shaft tibial osteotomies were used to create image-based finite element models. Virtual mechanical testing was used to compute postoperative gap-closing and 3D continuum strains representing compression (volumetric strain) and shear deformation (distortional strain). Callus mineralization was measured in zones in and around the osteotomy gap. Results. Gap-closing strains averaged 51% (mean) at the far cortex. Peak compressive volumetric strain averaged 32% and only a small tissue volume (average 0.3 cm. 3. ) within the gap experienced compressive strains > 10%. Distortional strains were much higher and more widespread, peaking at a mean of 115%, with a mean of 3.3 cm. 3. of tissue in and around the osteotomy experiencing distortional strains > 10%. Callus mineralization initiated outside the high-strain gap and was significantly lower within the fracture gap compared to around it at nine weeks. Conclusion. Ovine osteotomies can heal with high gap strains (> 10%) dominated by shear conditions. High gap strain appears to be a transient local limiter of osteogenesis, not a global inhibitor of secondary fracture repair. Cite this article: Bone Joint Res 2025;14(1):5–15

Introduction. Instability in ACL deficient knees can lead to medial compartment osteoarthritis. The risk of developing significant OA is 5x higher in knees with ACL deficiency. In associated Varus, there is quicker progression of the medial OA along with a varus thrust exerting strain on the ACL graft. The simultaneous valgus HTO and ACL reconstruction decompresses the medial tibiofemoral joint, corrects the mechanical-axis and reduces strain on the graft. Outcomes for this simultaneous procedure are still unclear in literature and we attempt evaluating its functional outcome. Methods. This Panel study was performed using data from 2019 to 2022 on 21 patients who had ACL insufficiency with Varus or medial OA and underwent a simultaneous Opening-wedge HTO with Arthroscopic ACL reconstruction. The mean follow-up was 2 years. The patients were evaluated with IKDC and Lysholm scores, Lachman test and ROM pre and post-operatively. The HKA was compared pre and post-operatively and the complications were evaluated. The progression of OA was evaluated with serial radiographs post-operatively. Results. There was a significant improvement in lifestyle and knee joint function post-operatively. The mechanical femorotibial angle was corrected from an average of 8.2° Varus to 0.8° Valgus. There was a significant improvement in IKDC and Lysholm scoring (IKDC score improved to 86.20 from 34.48 and the Lysholm score improved to 89 points from 37 points). There was significant improvement in the laxity which was evaluated by Lachman test. One patient had a clinical progression of medial-OA. No patients had non-union, graft or implant failure. Conclusion. Single stage HTO and ACL Reconstruction in patients with medial OA or Varus with ACL insufficiency is an option showing a satisfactory functional and radiological outcome along with activity scores

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This cross-sectional study aimed to investigate the in vivo ankle kinetic alterations in patients with concomitant chronic ankle instability (CAI) and osteochondral lesion of the talus (OLT), which may offer opportunities for clinician intervention in treatment and rehabilitation.

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Extracellular matrix (ECM) is a critical determinant of tissue mechanobiology, yet remains poorly characterized in joint tissues beyond cartilage in osteoarthritis (OA). This review aimed to define the composition and architecture of non-cartilage soft joint tissue structural ECM in human OA, and to compare the changes observed in humans with those seen in animal models of the disease.

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Electromagnetic induction heating has demonstrated in vitro antibacterial efficacy over biofilms on metallic biomaterials, although no in vivo studies have been published. Assessment of side effects, including thermal necrosis of adjacent tissue, would determine transferability into clinical practice. Our goal was to assess bone necrosis and antibacterial efficacy of induction heating on biofilm-infected implants in an in vivo setting.

The December 2024 Oncology Roundup³⁶⁰ looks at: Non-reversed great saphenous vein grafts for vascular reconstruction after resection of lower limb sarcoma; Detrimental effects of COVID-19 pandemic on patients with limb bone sarcoma: reference centre experience; Whole-body staging guidelines in sarcoma; Intraoperative marrow margin frozen section in limb bone sarcoma resection; Vacuum-assisted closure and paediatric oncological limb salvage; Treatment differences and long-term outcomes in adults and children with Ewing’s sarcoma; Survival, complications, and functional outcomes of uncemented distal femoral endoprosthesis with short, curved stem for patients with bone tumours.

Aim. Orthopedic implants play a tremendous role in fixing bone damages due to aging as well as fractures. However, these implants tend to get colonized by bacteria on the surface, leading to infections and subsequently prevention of healing and osteointegration. Recently, Roupie et al. showed that a nisin layer-by-layer based coating applied on biomaterials has both osteogenic and antibacterial properties. The Galleria mellonella larva is a well-known insect infection model that has been used to test the virulence of bacterial and fungal strains as well as for the high throughput screening of antimicrobial compounds against infections. Recently, we have developed an insect infection model with G. mellonella larvae to study implant-associated biofilm infections using Kirschner (K)-wires as implant material. Here, we would like to test the antibacterial capacity of nisin layer-by-layer based coatings on K-wires against Staphylococcus aureus in the G. mellonella larva implant infection model. Method. Prior to the implantation procedure, G. mellonella larvae are maintained at room temperature on wheat germ in an incubator. The larvae received bare titanium K-wires (uncoated), or either control-coated or nisin-coated K-wires. After one hour, the larvae were injected with 5×10. 5. S. aureus bacteria per larva (i.e., hematogenous implant infection model). Next, the larvae were incubated at 37. o. C in an incubator and the survival of the larvae was monitored for five days. Moreover, the number of bacteria on the implant surface and in the surrounding tissue was determined after 24h of incubation. Further, scanning electron microscopy (SEM) analyses were performed to study the effect of nisin on biofilm formation. Results. The larvae receiving the nisin-coated K-wires showed significantly higher survival rates compared to uncoated titanium K-wires, although not when compared to control-coated K-wires. A more than 1-log reduction in number of bacteria on the implant surface and in the surrounding tissue was observed in larvae receiving the nisin-coated K-wires, when compared to uncoated titanium K-wires SEM analysis showed reduced colonization of the bacteria nisin-coated K-wires compared to the controls. Conclusions. In conclusion, the antimicrobial nisin layer-by-layer based coating applied on titanium surfaces is able to prevent implant-related S. aureus biofilm infection in G. mellonella and is a promising antimicrobial strategy to prevent implant-related infections

Aim. Treatment of prosthetic joint infection (PJI) by systemic administration of high doses of long-term antibiotics often proves ineffective, causing severe side effects. Thus, we presented the phage Sb-1, which coding extracellular polymeric substances (EPS) degradation depolymerases, conjugated with rifampicin-loaded liposomes (Lip-RIF@Phage) by bio-orthogonal functionalization strategy to target biofilm (Figure1). Method. Methicillin-resistant Staphylococcus aureus (MRSA) biofilm was grown on porous glass beads for 24 h in vitro. After the biofilm formation, beads were exposed to 0.9% saline, then sonication. Quantitative and qualitative biofilm analyses were performed by colony counting, scanning electron microscopy and isothermal microcalorimetry. A rat model of total knee arthroplasty infected with the bioluminescent MRSA strain was developed as the PJI model to evaluate the efficacy of Lip-RIF@Phage anti-biofilm therapy in vivo, then the creatinine, alanine transaminase, and aspartate transaminase values were evaluated throughout the entire treatment process. Results. After treatment with Lip-RIF@Phage, no bacterial colonies were observed, consistent with findings from scanning electron microscopy. Similarly, isothermal microcalorimetry revealed no detectable heat following Lip-RIF@Phage treatment, aligning with these observations. In vivo experiments demonstrated a significant reduction in biofilm cell load compared to all other tested conditions, with no evidence of systemic toxicity on renal and liver functions attributed to Lip-RIF@Phage. Conclusions. The innovative depolymerase-phagobot nanosystem (Lip-RIF@Phage) exhibits remarkable efficacy in completely eliminating biofilm cells in vitro. It serves as an excellent carrier for antibiotic delivery, enhancing antibiotic penetration through biofilms and improving biofilm eradication efficacy. Furthermore, it enables personalized treatment strategies against biofilm-associated multidrug-resistant (MDR) infections by maximizing the effectiveness of any remaining sensitive antibiotics. For any tables or figures, please contact the authors directly

Aim. The aim of this study was to develop an in-house multiplex PCR real-time assay on the LightCycler 480 system (Roche, Basel, Switzerland) with the aim of rapid detection of common pathogens in prosthetic joint infections (PJI), followed by validation on clinical samples (sonication fluid and tissue biopsies) routinely collected for PJI diagnosis. Methods. Using the PrimerQuest and CLC WorkBench tool, we designed six primer sets with specific fluorescently labelled TaqMan probes for the nuc gene in different Staphylococcus species (S. aureus, S. epidermidis, S. capitis, S. lugdunensis, S. hominis, S. haemolyticus). In addition, primers previously developed by Renz et al. (2022) for C. acnes were integrated into our assay with internal control of isolation, leading to the development of specific mPCR assay with seven included targets. Analytical sensitivity and specificity were evaluated using reference bacterial strains. To determine the assay's limit of detection (LOD), we conducted serial dilutions of eluates containing known concentrations of bacterial DNA copies/µl. The overall LOD in spiked clinical samples, including sample preparation and DNA isolation on MagnaPure24, was measured through 10-fold serial dilutions (from 10. 9. to 10. -1. CFU/ml) including additional dilutions of 5000, 500, 50 and 5 CFU/ml. Results. The results with LOD in serial dilutions of eluates and spiked clinical samples, together with analytical sensitivity and specificity, are shown in Table 1. Conclusion. The mPCR assay showed excellent analytical sensitivity and specificity, but with considerably lower LOD after sample preparation and further DNA isolation in spiked clinical samples. Although still promising in diagnostics of acute infections, the use of mPCR could be challenging in chronic, low-grade infections with lower microbial burden. Nevertheless, PCR offers significant advantages in terms of speed and can shorten the time to result, especially for C. acnes infections. Additionally, it represents a promising complementary approach in patients with suspected PJI on antibiotic therapy with negative culture results. For any tables or figures, please contact the authors directly

Introduction. In specific conditions, infection may lead to bone loss and is difficult to treat. 1. Current clinical approaches rely on the introduction of antibiotics. While these may be effective, there are concerns regarding the rise of antimicrobial resistance. There is therefore interest in the development of antimicrobial bone graft substitutes for dental and trauma surgery. Aim & Objectives. The incorporation of zinc into biomaterials has been shown to confer broad spectrum antimicrobial activity, but this has not yet been applied to the development of a commercial bone graft substitute. The aim of this research was therefore to prepare and characterise a series of zinc-substituted nanoscale hydroxyapatite (nHA) materials, including evaluation of antimicrobial activity. Method. Zinc (Zn) substituted nHA materials were prepared (0, 5, 10, 15 & 20 mol.% Zn) using a wet chemical precipitation method with a rapid mixing. (2). The reaction was carried out using zinc hydroxide at pH 10. The suspension formed was washed and dried into both powder & paste forms. The resultant powders were characterized using transmission electron microscopy (TEM) and X-ray diffraction (XRD). The antimicrobial activity was evaluated against Staphylococcus aureus (S8650 strain - isolated from an osteomyelitis case), by two techniques. The Miles and Misra method was applied to determine the number of colony-forming units (CFUs) in bacterial suspensions incubated with pastes. Secondly, a biofilm initialization method was used to evaluate the capacity of the materials to prevent biofilm formation. One-way analysis of variance (ANOVA) was used for the statistical analysis and results with p-value < 0.05 were considered statistically significant. Results. XRD indicated the formation of pure hydroxyapatite with up to 10 mol.% Zn without any side products. However, when Zn was increased to 15 & 20 mol %, zinc oxide (ZnO) peaks were detected. The TEM showed nanoscale needle-like particles when Zn was increased compared to nHA particles. Regarding the antibacterial activity, ZnHA pastes at all concentrations caused a significant reduction in bacterial CFUs in a dose-dependent manner (50, 100 & 200 mg). Additionally, even the lowest zinc substitution (5 mol.%) significantly reduced biofilm formation. Conclusion. The results demonstrated a novel method to produce a Zn-substituted nHA that showed antimicrobial activity against a pathogen isolated from a bone infection

Aim. In trauma surgery, the development of biomaterial-associated infections (BAI) is one of the most common complications affecting trauma patients, requiring prolonged hospitalization and the intensive use of antibiotics. Following the attachment of bacteria on the surface of the biomaterial, the biofilm-forming bacteria could initiate a chronic implant-related infection. Despite the use of conventional local and systemic antibiotic therapies, persistent biofilms involve various resistance mechanisms that contribute to therapeutic failures. The development of in vivo chronic BAI models to optimize antibiofilm treatments is a major challenge. Indeed, the biofilm pathogenicity and the host response need to be finely regulated, and compatible with the animal lifestyle. Previously, a Galleria mellonella larvae model for the formation of an early-stage biofilm on the surface of a Kirschner (K)-wire was established. In the present study, two models of mature biofilm using clinical Staphylococcus aureus strains were assessed: one related to contaminated K-wires (in vitro biofilm maturation) and the second to hematogenous infections (in vivo biofilm maturation). Rifampicin was used as a standard drug for antibiofilm treatment. Method. In the first model, biofilms were formed following an incubation period (up to 7 days) in the CDC Biofilm Reactor (CBR, BioSurface Technologies). Then, after implantation of the pre-incubated K-wire in the larvae, rifampicin (80 mg/kg) was injected and the survival of the larvae was monitored. In the second model, biofilm formation was achieved after an incubation period (up to 7 days) inside the larvae and then, after removing the K-wires from the host, in vitro rifampicin susceptibility assays were performed (according to EUCAST). Results. The first model indicate that in vitro biofilm maturation affects the bacterial pathogenicity in the host, depending on the S. aureus strain used. Furthermore, the more the biofilm is matured, the more the rifampicin treatment efficiency is compromised. The second model shows that, despite the fast in vivo biofilm formation in the host, the number of bacteria, either attached to the surface of the K-wire surface or in surrounding tissue of the larvae, was not increased over time. Conclusions. Altogether, these results allow the establishment of biofilm models using G. mellonella larvae in order to understand the impact of biofilm maturation on both the bacterial pathogenicity and the efficiency of antibiofilm treatments

Introduction. This study aimed to evaluate the effectiveness of a novel intraoperative navigation platform for total knee arthroplasty (TKA) in restoring native knee joint kinematics and strains in the medial collateral ligament (MCL) and lateral collateral ligament (LCL) during squatting motions. Method. Six cadaver lower limbs underwent computed tomography scans to design patient-specific guides. Using these scans, bony landmarks and virtual single-line collateral ligaments were identified to provide intraoperative real-time feedback, aided in bone resection, implant alignment, tibiofemoral kinematics, and collateral ligament elongations, using the navigation platform. The specimens were subjected to squatting (35°-100°) motions on a physiological ex vivo knee simulator, maintaining a constant 110N vertical ankle load regulated by active quadriceps and bilateral hamstring actuators. Subsequently, each knee underwent a medially-stabilized TKA using the mechanical alignment technique, followed by a retest under the same conditions used preoperatively. Using a dedicated wand, MCL and LCL insertions—anterior, middle, and posterior bundles—were identified in relation to bone-pin markers. The knee kinematics and collateral ligament strains were analyzed from 3D marker trajectories captured by a six-camera optical system. Result. Both native and TKA conditions demonstrated similar patterns in tibial valgus orientation (Root Mean Square Error (RMSE=1.7°), patellar flexion (RMSE=1.2°), abduction (RMSE=0.5°), and rotation (RMSE=0.4°) during squatting (p>0.13). However, a significant difference was found in tibial internal rotation between 35° and 61° (p<0.045, RMSE=3.3°). MCL strains in anterior (RMSE=1.5%), middle (RMSE=0.8%), and posterior (RMSE=0.8%) bundles closely matched in both conditions, showing no statistical differences (p>0.05). Conversely, LCL strain across all bundles (RMSE<4.6%) exhibited significant differences from mid to deep flexion (p<0.048). Conclusion. The novel intraoperative navigation platform not only aims to achieve planned knee alignment but also assists in restoring native knee kinematics and collateral ligament behavior through real-time feedback. Acknowledgment. This study was funded by Medacta International (Castel San Pietro, Switzerland)

Introduction. Bone and joint infection (BJI) is often characterized by severe inflammation and progressive bone destruction. Osteocytes are the most numerous and long-lived bone cell type, and therefore represent a potentially important long-term reservoir of bacterial infection. Staphylococcus aureus is known to establish stable intracellular osteocytic infections, however, little is known about the less virulent yet second most prevalent BJI pathogen, S. epidermidis, associated with late-diagnosed, chronic BJI. Thus, this study sought to establish an in vitro model to study the infection characteristics of S. epidermidis in human osteocyte-like cells. Methods. SaOS2 cells (1 ×10. 4. cells/cm. 2. ) were grown to confluence either without differentiation, representing an osteoblast-like (OB) state (SaOS2-OB) or differentiated to an osteocyte-like stage (SaOS2-OY), using established methods. Four S. epidermidis strains used (ATCC-12228, ATCC-14990, ATCC-35984 and a clinical osteomyelitis strain RAH-SE1) were tested to be Lysostaphin-resistant, necessitating antibiotic (Levofloxacin) control of extracellular bacteria. Infection of host cells (OB or OY) was tested at three multiplicities of infection (MOI: 10, 100 and 1000). Extracellular bacteria were controlled by overnight incubation at a 10X minimum inhibitory concentration (MIC) of Levofloxacin and thereafter at 1XMIC. At each time point (days 1, 3, 5) viable intra- and extracellular bacteria were quantified. Result. All strains displayed similar intracellular infection and persistence capabilities in SaOS2-OB and SaOS2-OY. Independent of MOI, intracellular bacteria in SaOS2-OB decreased over time, becoming non-culturable by day 5. In contrast, SaOs2-OY displayed enhanced intracellular bacterial persistence at each time point. In the presence of increased Levofloxacin concentration (10XMIC), S. epidermidis could persist intracellularly for at least 14 days. Conclusion. This study showed for the first time that S. epidermidis can infect human osteocytes and persist intracellularly. Additionally, even a 10xMIC antibiotic concentration failed to eradicate intracellular bacteria, suggesting that persistence within osteocytes could contribute to treatment failure and establishment of chronic BJI

Introduction. Transosseous flexion-distraction injuries of the spine typically require surgical intervention by stabilizing the fractured vertebra during healing with a pedicle-screw-rod constructs. As healing is taking place the load shifts from the implant back to the spine. Monitoring the load-induced deflection of the rods over time would allow quantifiable postoperative assessment of healing progress without the need for radiation exposure or frequent hospital visits. This approach, previously demonstrated to be effective in assessing fracture healing in long bones and monitoring posterolateral spinal fusion in sheep, is now being investigated for its potential in evaluating lumbar vertebra transosseous fracture healing. Method. Six human cadaveric spines were instrumented with pedicle-screws and rods spanning L3 vertebra. The spine was loaded in Flexion-Extension (FE), Lateral-Bending (LB) and Axial-Rotation (AR) with an intact L3 vertebra (representing a healed vertebra) and after transosseous disruption, creating an AO type B1 fracture. The implant load on the rod was measured using an implantable strain sensor (Monitor) on one rod and on the contralateral rod by a strain gauge to validate the Monitor's measurements. In parallel the range of motion (ROM) was assessed. Result. The ROM increased significantly in all directions in the fractured model (p≤0.049). The Monitor measured a significant increase in implant load in FE (p=0.002) and LB (p=0.045), however, not in AR. The strain gauge detected an increased implant load not only in FE (p=0.001) and LB (p=0.016), but also in AR (p=0.047). The highest strain signal was found during LB for both, the Monitor, and the strain gauge. Conclusion. After a complete transosseous disruption of L3 vertebra the load on the implants was significantly higher than in the intact respectively healed state. Innovative implantable sensors could be used to monitor those changes allowing the assessment of healing progression based on quantifiable data rather than CT-imaging