Objectives. Advanced glycation end-products (AGEs) are a post-translational modification of collagen that form spontaneously in the skeletal matrix due to the presence of reducing sugars, such as glucose. The accumulation of AGEs leads to collagen cross-linking, which adversely affects bone quality and has been shown to play a major role in fracture risk. Thus, intervening in the formation and accumulation of AGEs may be a viable means of protecting bone quality. Methods. An in vitro model was used to examine the efficacy of two AGE-inhibitors, aminoguanidine (AG) and pyridoxamine (PM), on ageing human cortical bone. Mid-diaphyseal tibial cortical bone segments were obtained from female cadavers (n = 20, age range: 57 years to 97 years) and randomly subjected to one of four treatments: control; glucose only; glucose and AG; or glucose and PM. Following treatment, each specimen underwent mechanical testing under physiological conditions via reference point indentation, and AGEs were quantified by fluorescence. Results. Treatment with AG and PM showed a significant decrease in AGE content versus control groups, as well as a significant decrease in the change in indentation distance, a reliable parameter for analyzing bone strength, via two-way analysis of variance (ANOVA) (p < 0.05). Conclusions. The data suggest that AG and PM prevent AGE formation and subsequent biomechanical degradation in vitro. Modulation of AGEs may help to identify novel therapeutic targets to mitigate bone quality deterioration, especially deterioration due to ageing and in AGE-susceptible populations (e.g. diabetics). Cite this article: O. Abar, S. Dharmar, S. Y. Tang. The effect of aminoguanidine (AG) and pyridoxamine (PM) on ageing human cortical bone. Bone Joint Res 2018;7:105–110. DOI: 10.1302/2046-3758.71.BJR-2017-0135.R1

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. This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation. Methods. In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload. Results. Utilizing an OVX rat model, we observed significant alterations in bone mass and osseointegration due to VIT administration in aged rats with iron overload. The observed effects were concomitant with reductions in bone metabolism, oxidative stress, and inflammation. To elucidate whether these effects are associated with osteoclast and osteoblast activity, we conducted in vitro experiments using MC3T3-E1 cells and RAW264.7 cells. Our findings indicate that iron accumulation suppressed the activity of MC3T3-E1 while enhancing RAW264.7 function. Furthermore, iron overload significantly decreased oxidative stress levels; however, these detrimental effects can be mitigated by VIT treatment. Conclusion. Collectively, our data provide compelling evidence that VIT has the potential to reverse the deleterious consequences of iron overload on osseointegration and bone mass during ageing. Cite this article: Bone Joint Res 2024;13(9):427–440

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

Aims. Gap junction intercellular communication (GJIC) in osteocytes is impaired by oxidative stress, which is associated with age-related bone loss. Ageing is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, it is still unknown whether AOPP accumulation is involved in the impairment of osteocytes’ GJIC. This study aims to investigate the effect of AOPP accumulation on osteocytes’ GJIC in aged male mice and its mechanism. Methods. Changes in AOPP levels, expression of connexin43 (Cx43), osteocyte network, and bone mass were detected in 18-month-old and three-month-old male mice. Cx43 expression, GJIC function, mitochondria membrane potential, reactive oxygen species (ROS) levels, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation were detected in murine osteocyte-like cells (MLOY4 cells) treated with AOPPs. The Cx43 expression, osteocyte network, bone mass, and mechanical properties were detected in three-month-old mice treated with AOPPs for 12 weeks. Results. The AOPP levels were increased in aged mice and correlated with degeneration of osteocyte network, loss of bone mass, and decreased Cx43 expression. AOPP intervention induced NADPH oxidase activation and mitochondrial dysfunction, triggered ROS generation, reduced Cx43 expression, and ultimately impaired osteocytes’ GJIC, which were ameliorated by NADPH oxidase inhibitor apocynin, mitochondria-targeted superoxide dismutase mimetic (mito-TEMPO), and ROS scavenger N-acetyl cysteine. Chronic AOPP loading accelerated the degradation of osteocyte networks and decreased Cx43 expression, resulting in deterioration of bone mass and mechanical properties in vivo. Conclusion. Our study suggests that AOPP accumulation contributes to age-related impairment of GJIC in osteocytes of male mice, which may be part of the pathogenic mechanism responsible for bone loss during ageing. Cite this article: Bone Joint Res 2022;11(7):413–425

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

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

Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls.

Introduction

The pathogenesis of rotator cuff disease (RCD) is complex and not fully understood. This systematic review set out to summarise the histological and molecular changes that occur throughout the spectrum of RCD.

Aims. Achilles tendon re-rupture (ATRR) poses a significant risk of postoperative complication, even after a successful initial surgical repair. This study aimed to identify risk factors associated with Achilles tendon re-rupture following operative fixation. Methods. This retrospective cohort study analyzed a total of 43,287 patients from national health claims data spanning 2008 to 2018, focusing on patients who underwent surgical treatment for primary Achilles tendon rupture. Short-term ATRR was defined as cases that required revision surgery occurring between six weeks and one year after the initial surgical repair, while omitting cases with simultaneous infection or skin necrosis. Variables such as age, sex, the presence of Achilles tendinopathy, and comorbidities were systematically collected for the analysis. We employed multivariate stepwise logistic regression to identify potential risk factors associated with short-term ATRR. Results. From 2009 to 2018, the short-term re-rupture rate for Achilles tendon surgeries was 2.14%. Risk factors included male sex, younger age, and the presence of Achilles tendinopathy. Conclusion. This large-scale, big-data study reaffirmed known risk factors for short-term Achilles tendon re-rupture, specifically identifying male sex and younger age. Moreover, this study discovered that a prior history of Achilles tendinopathy emerges as an independent risk factor for re-rupture, even following initial operative fixation. Cite this article: Bone Joint Res 2024;13(7):315–320

Aims. The preventive effects of bisphosphonates on articular cartilage in non-arthritic joints are unclear. This study aimed to investigate the effects of oral bisphosphonates on the rate of joint space narrowing in the non-arthritic hip. Methods. We retrospectively reviewed standing whole-leg radiographs from patients who underwent knee arthroplasties from 2012 to 2020 at our institute. Patients with previous hip surgery, Kellgren–Lawrence grade ≥ II hip osteoarthritis, hip dysplasia, or rheumatoid arthritis were excluded. The rate of hip joint space narrowing was measured in 398 patients (796 hips), and the effects of the use of bisphosphonates were examined using the multivariate regression model and the propensity score matching (1:2) model. Results. A total of 45 of 398 (11.3%) eligible patients were taking an oral bisphosphonate at the time of knee surgery, with a mean age of 75.8 years (SD 6.2) in bisphosphonate users and 75.7 years (SD 6.8) in non-users. The mean joint space narrowing rate was 0.04 mm/year (SD 0.11) in bisphosphonate users and 0.12 mm/year (SD 0.25) in non-users (p < 0.001). In the multivariate model, age (standardized coefficient = 0.0867, p = 0.016) and the use of a bisphosphonate (standardized coefficient = −0.182, p < 0.001) were associated with the joint space narrowing rate. After successfully matching 43 bisphosphonate users and 86 non-users, the joint narrowing rate was smaller in bisphosphonate users (p < 0.001). Conclusion. The use of bisphosphonates is associated with decreased joint degeneration in non-arthritic hips after knee arthroplasty. Bisphosphonates slow joint degeneration, thus maintaining the thickness of joint cartilage in the normal joint or during the early phase of osteoarthritis. Cite this article: Bone Joint Res 2022;11(11):826–834

Aims. Spinopelvic characteristics influence the hip’s biomechanical behaviour. However, to date there is little knowledge defining what ‘normal’ spinopelvic characteristics are. This study aims to determine how static spinopelvic characteristics change with age and ethnicity among asymptomatic, healthy individuals. Methods. This systematic review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to identify English studies, including ≥ 18-year-old participants, without evidence of hip or spine pathology or a history of previous surgery or interventional treatment, documenting lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), and pelvic incidence (PI). From a total of 2,543 articles retrieved after the initial database search, 61 articles were eventually selected for data extraction. Results. When all ethnicities were combined the mean values for LL, SS, PT, and PI were: 47.4° (SD 11.0°), 35.8° (SD 7.8°), 14.0° (SD 7.2°), and 48.8° (SD 10°), respectively. LL, SS, and PT had statistically significant (p < 0.001) changes per decade at: −1.5° (SD 0.3°), −1.3° (SD 0.3°), and 1.4° (SD 0.1°). Asian populations had the largest age-dependent change in LL, SS, and PT compared to any other ethnicity per decade at: −1.3° (SD 0.3°) to −0.5° (SD 1.3°), –1.2° (SD 0.2°) to −0.3° (SD 0.3°), and 1.7° (SD 0.2°) versus 1.1° (SD 0.1°), respectively. Conclusion. Ageing alters the orientation between the spine and pelvis, causing LL, SS, and PT to modify their orientations in a compensatory mechanism to maintain sagittal alignment for balance when standing. Asian populations have the largest degree of age-dependent change to their spinopelvic parameters compared to any other ethnicity, likely due to their lower PI. Cite this article: Bone Joint Res 2023;12(4):231–244

Aims. The optimal choice of management for proximal humerus fractures (PHFs) has been increasingly discussed in the literature, and this work aimed to answer the following questions: 1) what are the incidence rates of PHF in the geriatric population in the USA; 2) what is the mortality rate after PHF in the elderly population, specifically for distinct treatment procedures; and 3) what factors influence the mortality rate?. Methods. PHFs occurring between 1 January 2009 and 31 December 2019 were identified from the Medicare physician service records. Incidence rates were determined, mortality rates were calculated, and semiparametric Cox regression was applied, incorporating 23 demographic, clinical, and socioeconomic covariates, to compare the mortality risk between treatments. Results. From 2009 to 2019, the incidence decreased by 11.85% from 300.4 cases/100,000 enrollees to 266.3 cases/100,000 enrollees, although this was not statistically significant (z = -1.47, p = 0.142). In comparison to matched Medicare patients without a PHF, but of the same five-year age group and sex, a mean survival difference of -17.3% was observed. The one-year mortality rate was higher after nonoperative treatment with 16.4% compared to surgical treatment with 9.3% (hazard ratio (HR) = 1.29, 95% confidence interval (CI) 1.23 to 1.36; p < 0.001) and to shoulder arthroplasty with 7.4% (HR = 1.45, 95% CI 1.33 to 1.58; p < 0.001). Statistically significant mortality risk factors after operative treatment included age older than 75 years, male sex, chronic obstructive pulmonary disease (COPD), cerebrovascular disease, chronic kidney disease, a concomitant fracture, congestive heart failure, and osteoporotic fracture. Conclusion. Mortality risk factors for distinct treatment modes after PHF in elderly patients could be identified, which may guide clinical decision-making. Cite this article: Bone Joint Res 2023;12(2):103–112

Aims. This observational cross-sectional study aimed to answer the following questions: 1) how has nonunion incidence developed from 2009 to 2019 in a nationwide cohort; 2) what is the age and sex distribution of nonunions for distinct anatomical nonunion localizations; and 3) how high were the costs for surgical nonunion treatment in a level 1 trauma centre in Germany?. Methods. Data consisting of annual International Classification of Diseases (ICD)-10 diagnosis codes from German medical institutions from 2009 to 2019, provided by the Federal Statistical Office of Germany (Destatis), were analyzed. Nonunion incidence was calculated for anatomical localization, sex, and age groups. Incidence rate ratios (IRRs) were determined and compared with a two-sample z-test. Diagnosis-related group (DRG)-reimbursement and length of hospital stay were retrospectively retrieved for each anatomical localization, considering 210 patients. Results. In 2019, a total of 11,840 nonunion cases (17.4/100,000 inhabitants) were treated. In comparison to 2018, the incidence of nonunion increased by 3% (IRR 1.03, 95% confidence interval (CI) 0.53 to 1.99, p = 0.935). The incidence was higher for male cases (IRR female/male: 0.79, 95% CI 0.76 to 0.82, p = 0.484). Most nonunions occurred at the pelvic and hip region (3.6/100,000 inhabitants, 95% CI 3.5 to 3.8), followed by the ankle and foot as well as the hand (2.9/100,000 inhabitants each). Mean estimated DRG reimbursement for in-hospital treatment of nonunions was highest for nonunions at the pelvic and hip region (€8,319 (SD 2,410), p < 0.001). Conclusion. Despite attempts to improve fracture treatment in recent years, nonunions remain a problem for orthopaedic and trauma surgery, with a stable incidence throughout the last decade. Cite this article: Bone Joint Res 2022;11(8):541–547

Aims. This study investigates the use of the metabolic equivalent of task (MET) score in a young hip arthroplasty population, and its ability to capture additional benefit beyond the ceiling effect of conventional patient-reported outcome measures. Methods. From our electronic database of 751 hip arthroplasty procedures, 221 patients were included. Patients were excluded if they had revision surgery, an alternative hip procedure, or incomplete data either preoperatively or at one-year follow-up. Included patients had a mean age of 59.4 years (SD 11.3) and 54.3% were male, incorporating 117 primary total hip and 104 hip resurfacing arthroplasty operations. Oxford Hip Score (OHS), EuroQol five-dimension questionnaire (EQ-5D), and the MET were recorded preoperatively and at one-year follow-up. The distribution was examined reporting the presence of ceiling and floor effects. Validity was assessed correlating the MET with the other scores using Spearman’s rank correlation coefficient and determining responsiveness. A subgroup of 93 patients scoring 48/48 on the OHS were analyzed by age, sex, BMI, and preoperative MET using the other metrics to determine if differences could be established despite scoring identically on the OHS. Results. Postoperatively the OHS and EQ-5D demonstrate considerable negatively skewed distributions with ceiling effects of 41.6% and 53.8%, respectively. The MET was normally distributed postoperatively with no relevant ceiling effect. Weak-to-moderate significant correlations were found between the MET and the other two metrics. In the 48/48 subgroup, no differences were found comparing groups with the EQ-5D, however significantly higher mean MET scores were demonstrated for patients aged < 60 years (12.7 (SD 4.7) vs 10.6 (SD 2.4), p = 0.008), male patients (12.5 (SD 4.5) vs 10.8 (SD 2.8), p = 0.024), and those with preoperative MET scores > 6 (12.6 (SD 4.2) vs 11.0 (SD 3.3), p = 0.040). Conclusion. The MET is normally distributed in patients following hip arthroplasty, recording levels of activity which are undetectable using the OHS. Cite this article: Bone Joint Res 2022;11(5):317–326

Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA. Cite this article: Bone Joint Res 2023;12(9):536–545

Aims. This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD). Methods. The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions. Results. A total of 56 EP-DEGs were identified in the differential expression analysis. EP-DEGs were enriched in the extracellular structure organization, ageing, collagen-activated signalling pathway, PI3K-Akt signalling pathway, and AGE-RAGE signalling pathway. PPI network analysis showed that the top ten hub EP-DEGs are closely related to IDD. Correlation analysis also demonstrated a significant correlation between the ten hub EP-DEGs (p＜0.05), which were selected to construct TF–gene interaction and TF–miRNA coregulatory networks. In addition, ten candidate drugs were screened for the treatment of IDD. Conclusion. The findings clarify the roles of extracellular proteins in IDD and highlight their potential as promising novel therapeutic targets. Cite this article: Bone Joint Res 2023;12(9):522–535

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. To determine the major risk factors for unplanned reoperations (UROs) following corrective surgery for adult spinal deformity (ASD) and their interactions, using machine learning-based prediction algorithms and game theory. Methods. Patients who underwent surgery for ASD, with a minimum of two-year follow-up, were retrospectively reviewed. In total, 210 patients were included and randomly allocated into training (70% of the sample size) and test (the remaining 30%) sets to develop the machine learning algorithm. Risk factors were included in the analysis, along with clinical characteristics and parameters acquired through diagnostic radiology. Results. Overall, 152 patients without and 58 with a history of surgical revision following surgery for ASD were observed; the mean age was 68.9 years (SD 8.7) and 66.9 years (SD 6.6), respectively. On implementing a random forest model, the classification of URO events resulted in a balanced accuracy of 86.8%. Among machine learning-extracted risk factors, URO, proximal junction failure (PJF), and postoperative distance from the posterosuperior corner of C7 and the vertical axis from the centroid of C2 (SVA) were significant upon Kaplan-Meier survival analysis. Conclusion. The major risk factors for URO following surgery for ASD, i.e. postoperative SVA and PJF, and their interactions were identified using a machine learning algorithm and game theory. Clinical benefits will depend on patient risk profiles. Cite this article: Bone Joint Res 2023;12(4):245–255

Aims. The aim of this investigation was to compare risk of infection in both cemented and uncemented hemiarthroplasty (HA) as well as in total hip arthroplasty (THA) following femoral neck fracture. Methods. Data collection was performed using the German Arthroplasty Registry (EPRD). In HA and THA following femoral neck fracture, fixation method was divided into cemented and uncemented prostheses and paired according to age, sex, BMI, and the Elixhauser Comorbidity Index using Mahalanobis distance matching. Results. Overall in 13,612 cases of intracapsular femoral neck fracture, 9,110 (66.9%) HAs and 4,502 (33.1%) THAs were analyzed. Infection rate in HA was significantly reduced in cases with use of antibiotic-loaded cement compared with uncemented fixated prosthesis (p = 0.013). In patients with THA no statistical difference between cemented and uncemented prosthesis was registered, however after one year 2.4% of infections were detected in uncemented and 2.1% in cemented THA. In the subpopulation of HA after one year, 1.9% of infections were registered in cemented and 2.8% in uncemented HA. BMI (p = 0.001) and Elixhauser Comorbidity Index (p < 0.003) were identified as risk factors of periprosthetic joint infection (PJI), while in THA cemented prosthesis also demonstrated an increased risk within the first 30 days (hazard ratio (HR) = 2.73; p = 0.010). Conclusion. The rate of infection after intracapsular femoral neck fracture was statistically significantly reduced in patients treated by antibiotic-loaded cemented HA. Particularly for patients with multiple risk factors for the development of a PJI, the usage of antibiotic-loaded bone cement seems to be a reasonable procedure for prevention of infection. Cite this article: Bone Joint Res 2023;12(5):331–338