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Aims

This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously.

Methods

Using weighted gene co-expression network analysis (WGCNA), we analyzed datasets from the Gene Expression Omnibus (GEO) database to identify co-expressed gene modules in OB and OP. These modules underwent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction analysis to discover Hub genes. Machine learning refined the gene selection, with further validation using additional datasets. Single-cell analysis emphasized specific cell subpopulations, and enzyme-linked immunosorbent assay (ELISA), protein blotting, and cellular staining were used to investigate key genes.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 559 - 572
8 Oct 2024
Wu W Zhao Z Wang Y Liu M Zhu G Li L

Aims

This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels.

Methods

A closed tibial fracture model was established using 12 male Japanese white rabbits, and divided into elastic and stiff fixation groups based on different fixation methods. Two weeks after the operation, a radiograph and pathological examination of callus tissue were used to evaluate fracture healing. Then, the differentially expressed proteins (DEPs) were examined in the callus using proteomics. Finally, in vitro cell experiments were conducted to investigate hub proteins involved in this process.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 535 - 545
2 Oct 2024
Zou C Guo W Mu W Wahafu T Li Y Hua L Xu B Cao L

Aims

We aimed to determine the concentrations of synovial vancomycin and meropenem in patients treated by single-stage revision combined with intra-articular infusion following periprosthetic joint infection (PJI), thereby validating this drug delivery approach.

Methods

We included 14 patients with PJI as noted in their medical records between November 2021 and August 2022, comprising eight hip and seven knee joint infections, with one patient experiencing bilateral knee infections. The patients underwent single-stage revision surgery, followed by intra-articular infusion of vancomycin and meropenem (50,000 µg/ml). Synovial fluid samples were collected to assess antibiotic concentrations using high-performance liquid chromatography.


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1044 - 1049
1 Oct 2024
Abelleyra Lastoria DA Ogbolu C Olatigbe O Beni R Iftikhar A Hing CB

Aims

To determine whether obesity and malnutrition have a synergistic effect on outcomes from skeletal trauma or elective orthopaedic surgery.

Methods

Electronic databases including MEDLINE, Global Health, Embase, Web of Science, ScienceDirect, and PEDRo were searched up to 14 April 2024, as well as conference proceedings and the reference lists of included studies. Studies were appraised using tools according to study design, including the Oxford Levels of Evidence, the Institute of Health Economics case series quality appraisal checklist, and the CLARITY checklist for cohort studies. Studies were eligible if they reported the effects of combined malnutrition and obesity on outcomes from skeletal trauma or elective orthopaedic surgery.


Bone & Joint Research
Vol. 13, Issue 9 | Pages 497 - 506
16 Sep 2024
Hsieh H Yen H Hsieh W Lin C Pan Y Jaw F Janssen SJ Lin W Hu M Groot O

Aims. Advances in treatment have extended the life expectancy of patients with metastatic bone disease (MBD). Patients could experience more skeletal-related events (SREs) as a result of this progress. Those who have already experienced a SRE could encounter another local management for a subsequent SRE, which is not part of the treatment for the initial SRE. However, there is a noted gap in research on the rate and characteristics of subsequent SREs requiring further localized treatment, obligating clinicians to extrapolate from experiences with initial SREs when confronting subsequent ones. This study aimed to investigate the proportion of MBD patients developing subsequent SREs requiring local treatment, examine if there are prognostic differences at the initial treatment between those with single versus subsequent SREs, and determine if clinical, oncological, and prognostic features differ between initial and subsequent SRE treatments. Methods. This retrospective study included 3,814 adult patients who received local treatment – surgery and/or radiotherapy – for bone metastasis between 1 January 2010 and 31 December 2019. All included patients had at least one SRE requiring local treatment. A subsequent SRE was defined as a second SRE requiring local treatment. Clinical, oncological, and prognostic features were compared between single SREs and subsequent SREs using Mann-Whitney U test, Fisher’s exact test, and Kaplan–Meier curve. Results. Of the 3,814 patients with SREs, 3,159 (83%) patients had a single SRE and 655 (17%) patients developed a subsequent SRE. Patients who developed subsequent SREs generally had characteristics that favoured longer survival, such as higher BMI, higher albumin levels, fewer comorbidities, or lower neutrophil count. Once the patient got to the point of subsequent SRE, their clinical and oncological characteristics and one-year survival (28%) were not as good as those with only a single SRE (35%; p < 0.001), indicating that clinicians’ experiences when treating the initial SRE are not similar when treating a subsequent SRE. Conclusion. This study found that 17% of patients required treatments for a second, subsequent SRE, and the current clinical guideline did not provide a specific approach to this clinical condition. We observed that referencing the initial treatment, patients in the subsequent SRE group had longer six-week, 90-day, and one-year median survival than patients in the single SRE group. Once patients develop a subsequent SRE, they have a worse one-year survival rate than those who receive treatment for a single SRE. Future research should identify prognostic factors and assess the applicability of existing survival prediction models for better management of subsequent SREs. Cite this article: Bone Joint Res 2024;13(9):497–506


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 1021 - 1030
1 Sep 2024
Oto J Herranz R Fuertes M Plana E Verger P Baixauli F Amaya JV Medina P

Aims

Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers.

Methods

We prospectively recruited 107 patients in the preoperative period of prosthetic surgery, 71 with a suspicion of PJI and 36 who underwent arthroplasty for non-septic indications as controls, and obtained citrated plasma. PJI was confirmed in 50 patients. We measured NET markers, inflammation markers, DNaseI activity, haemostatic markers, and the thrombin generation test (TGT). We analyzed the ability of plasma from confirmed PJI and controls to induce NETosis and to degrade in vitro-generated NETs, and explored the therapeutic restoration of the impairment to degrade NETs of PJI plasma with recombinant human DNaseI. Finally, we assessed the contribution of these markers to the diagnosis of PJI.


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 935 - 941
1 Sep 2024
Ailaney N Guirguis PG Ginnetti JG Balkissoon R Myers TG Ramirez G Thirukumaran CP Ricciardi BF

Aims

The purpose of this study was to determine the association between prior sleeve gastrectomy in patients undergoing primary total hip and knee arthroplasty, and 90-day complications, incidence of revision arthroplasty, and patient-reported outcome scores at final follow-up.

Methods

This is a retrospective, single-centre analysis. Patients undergoing primary hip or knee arthroplasty with a prior sleeve gastrectomy were eligible for inclusion (n = 80 patients). A morbidly obese control group was established from the same institutional registry using a 1:2 match, for cases:controls with arthroplasty based on propensity score using age, sex, pre-sleeve gastrectomy BMI, Current Procedural Terminology code to identify anatomical location, and presurgical haemoglobin A1C. Outcomes included 90-day complications, incidence of revision arthroplasty, and patient-reported outcome scores at final follow-up. Multivariable logistic regressions evaluated associations of underlying preoperative demographic and treatment characteristics with outcomes.


Bone & Joint Research
Vol. 13, Issue 8 | Pages 372 - 382
1 Aug 2024
Luger M Böhler C Puchner SE Apprich S Staats K Windhager R Sigmund IK

Aims

Serum inflammatory parameters are widely used to aid in diagnosing a periprosthetic joint infection (PJI). Due to their limited performances in the literature, novel and more accurate biomarkers are needed. Serum albumin-to-globulin ratio (AGR) and serum CRP-to-albumin ratio (CAR) have previously been proposed as potential new parameters, but results were mixed. The aim of this study was to assess the diagnostic accuracy of AGR and CAR in diagnosing PJI and to compare them to the established and widely used marker CRP.

Methods

From 2015 to 2022, a consecutive series of 275 cases of revision total hip (n = 129) and knee arthroplasty (n = 146) were included in this retrospective cohort study. Based on the 2021 European Bone and Joint Infection Society (EBJIS) definition, 144 arthroplasties were classified as septic. Using receiver operating characteristic curve (ROC) analysis, the ideal thresholds and diagnostic performances were calculated. The areas under the curve (AUCs) were compared using the z-test.


Bone & Joint 360
Vol. 13, Issue 3 | Pages 35 - 36
3 Jun 2024

The June 2024 Spine Roundup360 looks at: Intraoperative navigation increases the projected lifetime cancer risk in patients undergoing surgery for adolescent idiopathic scoliosis; Intrawound vancomycin powder reduces delayed deep surgical site infections following posterior spinal fusion for adolescent idiopathic scoliosis; Characterizing negative online reviews of spine surgeons; Proximal junctional failure after surgical instrumentation in adult spinal deformity: biomechanical assessment of proximal instrumentation stiffness; Nutritional supplementation and wound healing: a randomized controlled trial.


The Bone & Joint Journal
Vol. 106-B, Issue 5 | Pages 492 - 500
1 May 2024
Miwa S Yamamoto N Hayashi K Takeuchi A Igarashi K Tada K Taniguchi Y Morinaga S Asano Y Tsuchiya H

Aims

Surgical site infection (SSI) after soft-tissue sarcoma (STS) resection is a serious complication. The purpose of this retrospective study was to investigate the risk factors for SSI after STS resection, and to develop a nomogram that allows patient-specific risk assessment.

Methods

A total of 547 patients with STS who underwent tumour resection between 2005 and 2021 were divided into a development cohort and a validation cohort. In the development cohort of 402 patients, the least absolute shrinkage and selection operator (LASSO) regression model was used to screen possible risk factors of SSI. To select risk factors and construct the prediction nomogram, multivariate logistic regression was used. The predictive power of the nomogram was evaluated by receiver operating curve (ROC) analysis in the validation cohort of 145 patients.


Bone & Joint Open
Vol. 5, Issue 4 | Pages 350 - 360
23 Apr 2024
Wang S Chen Z Wang K Li H Qu H Mou H Lin N Ye Z

Aims

Radiotherapy is a well-known local treatment for spinal metastases. However, in the presence of postoperative systemic therapy, the efficacy of radiotherapy on local control (LC) and overall survival (OS) in patients with spinal metastases remains unknown. This study aimed to evaluate the clinical outcomes of post-surgical radiotherapy for spinal metastatic non-small-cell lung cancer (NSCLC) patients, and to identify factors correlated with LC and OS.

Methods

A retrospective, single-centre review was conducted of patients with spinal metastases from NSCLC who underwent surgery followed by systemic therapy at our institution from January 2018 to September 2022. Kaplan-Meier analysis and log-rank tests were used to compare the LC and OS between groups. Associated factors for LC and OS were assessed using Cox proportional hazards regression analysis.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 184 - 192
18 Apr 2024
Morita A Iida Y Inaba Y Tezuka T Kobayashi N Choe H Ike H Kawakami E

Aims

This study was designed to develop a model for predicting bone mineral density (BMD) loss of the femur after total hip arthroplasty (THA) using artificial intelligence (AI), and to identify factors that influence the prediction. Additionally, we virtually examined the efficacy of administration of bisphosphonate for cases with severe BMD loss based on the predictive model.

Methods

The study included 538 joints that underwent primary THA. The patients were divided into groups using unsupervised time series clustering for five-year BMD loss of Gruen zone 7 postoperatively, and a machine-learning model to predict the BMD loss was developed. Additionally, the predictor for BMD loss was extracted using SHapley Additive exPlanations (SHAP). The patient-specific efficacy of bisphosphonate, which is the most important categorical predictor for BMD loss, was examined by calculating the change in predictive probability when hypothetically switching between the inclusion and exclusion of bisphosphonate.


Bone & Joint Open
Vol. 5, Issue 3 | Pages 210 - 217
13 Mar 2024
Mthethwa PG Marais LC Aldous CM

Aims

The aim of this study is to determine the predictors of overall survival (OS) and predictive factors of poor prognosis of conventional high-grade osteosarcoma of the limbs in a single-centre in South Africa.

Methods

We performed a retrospective cross-sectional analysis to identify the prognostic factors that predict the OS of patients with histologically confirmed high-grade conventional osteosarcoma of the limbs over ten years. We employed the Cox proportional regression model and the Kaplan-Meier method for statistical analysis.


Bone & Joint Research
Vol. 13, Issue 2 | Pages 52 - 65
1 Feb 2024
Yao C Sun J Luo W Chen H Chen T Chen C Zhang B Zhang Y

Aims

To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism.

Methods

In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed.


The Bone & Joint Journal
Vol. 106-B, Issue 2 | Pages 203 - 211
1 Feb 2024
Park JH Won J Kim H Kim Y Kim S Han I

Aims. This study aimed to compare the performance of survival prediction models for bone metastases of the extremities (BM-E) with pathological fractures in an Asian cohort, and investigate patient characteristics associated with survival. Methods. This retrospective cohort study included 469 patients, who underwent surgery for BM-E between January 2009 and March 2022 at a tertiary hospital in South Korea. Postoperative survival was calculated using the PATHFx3.0, SPRING13, OPTIModel, SORG, and IOR models. Model performance was assessed with area under the curve (AUC), calibration curve, Brier score, and decision curve analysis. Cox regression analyses were performed to evaluate the factors contributing to survival. Results. The SORG model demonstrated the highest discriminatory accuracy with AUC (0.80 (95% confidence interval (CI) 0.76 to 0.85)) at 12 months. In calibration analysis, the PATHfx3.0 and OPTIModel models underestimated survival, while the SPRING13 and IOR models overestimated survival. The SORG model exhibited excellent calibration with intercepts of 0.10 (95% CI -0.13 to 0.33) at 12 months. The SORG model also had lower Brier scores than the null score at three and 12 months, indicating good overall performance. Decision curve analysis showed that all five survival prediction models provided greater net benefit than the default strategy of operating on either all or no patients. Rapid growth cancer and low serum albumin levels were associated with three-, six-, and 12-month survival. Conclusion. State-of-art survival prediction models for BM-E (PATHFx3.0, SPRING13, OPTIModel, SORG, and IOR models) are useful clinical tools for orthopaedic surgeons in the decision-making process for the treatment in Asian patients, with SORG models offering the best predictive performance. Rapid growth cancer and serum albumin level are independent, statistically significant factors contributing to survival following surgery of BM-E. Further refinement of survival prediction models will bring about informed and patient-specific treatment of BM-E. Cite this article: Bone Joint J 2024;106-B(2):203–211


Bone & Joint Research
Vol. 13, Issue 1 | Pages 28 - 39
10 Jan 2024
Toya M Kushioka J Shen H Utsunomiya T Hirata H Tsubosaka M Gao Q Chow SK Zhang N Goodman SB

Aims

Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice.

Methods

We used a murine model of chronic inflammation induced by continuous intramedullary delivery of lipopolysaccharide-contaminated polyethylene particles (cPE) using an osmotic pump. Specimens were evaluated using micro-CT and histomorphometric analyses. Sex-specific osteogenic and osteoclastic differentiation potentials were also investigated in vitro, including alkaline phosphatase, Alizarin Red, tartrate-resistant acid phosphatase staining, and gene expression using reverse transcription polymerase chain reaction (RT-PCR).


Bone & Joint Open
Vol. 4, Issue 11 | Pages 899 - 905
24 Nov 2023
Orfanos G Nantha Kumar N Redfern D Burston B Banerjee R Thomas G

Aims

We aim to evaluate the usefulness of postoperative blood tests by investigating the incidence of abnormal results following total joint replacement (TJR), as well as identifying preoperative risk factors for abnormal blood test results postoperatively, especially pertaining to anaemia and acute kidney injury (AKI).

Methods

This is a retrospective cohort study of patients who had elective TJR between January and December 2019 at a tertiary centre. Data gathered included age at time of surgery, sex, BMI, American Society of Anesthesiologists (ASA) grade, preoperative and postoperative laboratory test results, haemoglobin (Hgb), white blood count (WBC), haematocrit (Hct), platelets (Plts), sodium (Na+), potassium (K+), creatinine (Cr), estimated glomerular filtration rate (eGFR), and Ferritin (ug/l). Abnormal blood tests, AKI, electrolyte imbalance, anaemia, transfusion, reoperation, and readmission within one year were reported.


Bone & Joint Open
Vol. 4, Issue 11 | Pages 832 - 838
3 Nov 2023
Pichler L Li Z Khakzad T Perka C Pumberger M Schömig F

Aims

Implant-related postoperative spondylodiscitis (IPOS) is a severe complication in spine surgery and is associated with high morbidity and mortality. With growing knowledge in the field of periprosthetic joint infection (PJI), equivalent investigations towards the management of implant-related infections of the spine are indispensable. To our knowledge, this study provides the largest description of cases of IPOS to date.

Methods

Patients treated for IPOS from January 2006 to December 2020 were included. Patient demographics, parameters upon admission and discharge, radiological imaging, and microbiological results were retrieved from medical records. CT and MRI were analyzed for epidural, paravertebral, and intervertebral abscess formation, vertebral destruction, and endplate involvement. Pathogens were identified by CT-guided or intraoperative biopsy, intraoperative tissue sampling, or implant sonication.


The Bone & Joint Journal
Vol. 105-B, Issue 11 | Pages 1149 - 1158
1 Nov 2023
Chen B Zhang JH Duckworth AD Clement ND

Aims. Hip fractures are a major cause of morbidity and mortality, and malnutrition is a crucial determinant of these outcomes. This meta-analysis aims to determine whether oral nutritional supplementation (ONS) improves postoperative outcomes in older patients with a hip fracture. Methods. A systematic literature search was conducted in August 2022. ONS was defined as high protein-based diet strategies containing (or not containing) carbohydrates, fat, vitamins, and minerals. Randomized trials documenting ONS in older patients with hip fracture (aged ≥ 50 years) were included. Two reviewers evaluated study eligibility, conducted data extraction, and assessed study quality. Results. There were 812 studies identified, of which 18 studies involving 1,522 patients met the inclusion criteria. The overall meta-analysis demonstrated that ONS was associated with significantly elevated albumin levels (weighted mean difference (WMD) 1.24 (95% confidence interval (CI) 0.95 to 1.53)), as well as a significant risk reduction in infective complications (odds ratio (OR) 0.54 (95% CI 0.39 to 0.76)), pressure ulcers (OR 0.54 (95% CI 0.33 to 0.88)), and total complications (OR 0.57 (95% CI 0.42 to 0.79)). Length of hospital stay (LOS) was also significantly reduced (WMD -2.36 (95% CI -4.14 to -0.58)), particularly in rehabilitation LOS (WMD -4.17 (95% CI -7.08 to -1.26)). There was a tendency towards a lower mortality risk (OR 0.93 (95% CI 0.62 to 1.4)) and readmission (OR 0.52 (95% CI 0.16 to 1.73)), although statistical significance was not achieved (p = 0.741 and p = 0.285, respectively). The overall compliance with ONS ranged from 64.7% to 100%, but no factors influencing compliance were identified. Conclusion. This meta-analysis is the first to quantitatively demonstrate that ONS could nearly halve the risk of infective complications, pressure ulcers, total complications, as well as improve serum albumin and reduce LOS. ONS should be a regular and integrated part of the perioperative care of these patients, especially given that the compliance with ONS is acceptable. Cite this article: Bone Joint J 2023;105-B(11):1149–1158


Bone & Joint Research
Vol. 12, Issue 10 | Pages 667 - 676
19 Oct 2023
Forteza-Genestra MA Antich-Rosselló M Ramis-Munar G Calvo J Gayà A Monjo M Ramis JM

Aims

Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants.

Methods

pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized by nanoparticle tracking analysis (NTA), protein content, and purity. OA conditions were induced in human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml tumour necrosis factor alpha (TNFα)) and treated with 1 × 109 particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG), and collagen content were quantified, and a histological study was performed. EV uptake was monitored using PKH26 labelled EVs.