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Bone & Joint Research
Vol. 12, Issue 6 | Pages 387 - 396
26 Jun 2023
Xu J Si H Zeng Y Wu Y Zhang S Shen B

Aims. Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease. Methods. We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes. Results. TWAS identified 295 genes with permutation p-values < 0.05 for skeletal muscle and 79 genes associated for the whole blood, such as RCHY1 (PTWAS = 0.001). Those genes were enriched in 112 gene ontology (GO) terms and five Kyoto Encyclopedia of Genes and Genomes pathways, such as ‘chemical carcinogenesis - reactive oxygen species’ (LogP value = −2.139). Further comparing the TWAS significant genes with the differentially expressed genes identified by mRNA expression profiles of LSS found 18 overlapped genes, such as interleukin 15 receptor subunit alpha (IL15RA) (PTWAS = 0.040, PmRNA = 0.010). Moreover, 71 common GO terms were detected for the enrichment results of TWAS and mRNA expression profiles, such as negative regulation of cell differentiation (LogP value = −2.811). Conclusion. This study revealed the genetic mechanism behind the pathological changes in LSS, and may provide novel insights for the early diagnosis and intervention of LSS. Cite this article: Bone Joint Res 2023;12(6):387–396


Bone & Joint Open
Vol. 5, Issue 10 | Pages 825 - 831
3 Oct 2024
Afghanyar Y Afghanyar B Loweg L Drees P Gercek E Dargel J Rehbein P Kutzner KP

Aims. Limited implant survival due to aseptic cup loosening is most commonly responsible for revision total hip arthroplasty (THA). Advances in implant designs and materials have been crucial in addressing those challenges. Vitamin E-infused highly cross-linked polyethylene (VEPE) promises strong wear resistance, high oxidative stability, and superior mechanical strength. Although VEPE monoblock cups have shown good mid-term performance and excellent wear patterns, long-term results remain unclear. This study evaluated migration and wear patterns and clinical and radiological outcomes at a minimum of ten years’ follow-up. Methods. This prospective observational study investigated 101 cases of primary THA over a mean duration of 129 months (120 to 149). At last follow-up, 57 cases with complete clinical and radiological outcomes were evaluated. In all cases, the acetabular component comprised an uncemented titanium particle-coated VEPE monoblock cup. Patients were assessed clinically and radiologically using the Harris Hip Score, visual analogue scale (pain and satisfaction), and an anteroposterior radiograph. Cup migration and polyethylene wear were measured using Einzel-Bild-Röntgen-Analyze software. All complications and associated treatments were documented until final follow-up. Results. Clinical assessment showed persistent major improvement in all scores. On radiological assessment, only one case showed a lucent line (without symptoms). At last follow-up, wear and migration were below the critical thresholds. No cup-related revisions were needed, indicating an outstanding survival rate of 100%. Conclusion. Isoelastic VEPE cups offer high success rates and may prevent osteolysis, aseptic loosening, and the need for revision surgeries in the long term. However, longer follow-up is needed to validate our findings and confirm the advantages offered by this cup. Cite this article: Bone Jt Open 2024;5(10):825–831


Bone & Joint Research
Vol. 13, Issue 10 | Pages 596 - 610
21 Oct 2024
Toegel S Martelanz L Alphonsus J Hirtler L Gruebl-Barabas R Cezanne M Rothbauer M Heuberer P Windhager R Pauzenberger L

Aims. This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated. Methods. Specimens of the humeral head and synovial tissue from 12 patients with OmA, seven patients with CTA, and four body donors were processed histologically for examination using different histopathological scores. Osteochondral sections were immunohistochemically stained for collagen type I, collagen type II, collagen neoepitope C1,2C, collagen type X, and osteocalcin, prior to semiquantitative analysis. Matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 levels were analyzed in synovial fluid using enzyme-linked immunosorbent assay (ELISA). Results. Cartilage degeneration of the humeral head was associated with the histological presentation of: 1) pannus overgrowing the cartilage surface; 2) pores in the subchondral bone plate; and 3) chondrocyte clusters in OmA patients. In contrast, hyperplasia of the synovial lining layer was revealed as a significant indicator of inflammatory processes predominantly in CTA. The abundancy of collagen I, collagen II, and the C1,2C neoepitope correlated significantly with the histopathological degeneration of humeral head cartilage. No evidence for differences in MMP levels between OmA and CTA patients was found. Conclusion. This study provides a comprehensive histological characterization of humeral cartilage and synovial tissue within the glenohumeral joint, both in normal and diseased states. It highlights synovitis and pannus formation as histopathological hallmarks of OmA and CTA, indicating their roles as drivers of joint inflammation and cartilage degradation, and as targets for therapeutic strategies such as rotator cuff reconstruction and synovectomy. Cite this article: Bone Joint Res 2024;13(10):596–610


Bone & Joint Research
Vol. 12, Issue 12 | Pages 722 - 733
6 Dec 2023
Fu T Chen W Wang Y Chang C Lin T Wong C

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


Aims. In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD. Methods. An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD. Results. A correlation between DDIT4 expression levels and disc degeneration was shown with human nucleus pulposus and needle-punctured rat disc specimens. We confirmed that DDIT4 was responsible for activating the ROS-TXNIP-NLRP3 axis during oxidative stress-induced pyroptosis in rat nucleus pulposus in vitro. Mitochondria were damaged during oxidative stress, and DDIT4 contributed to mitochondrial damage and ROS production. In addition, siDDIT4@G5-P-HA hydrogels showed good delivery activity of siDDIT4 to NPCs. In vitro studies illustrated the potential of the siDDIT4@G5-P-HA hydrogel for alleviating IVDD in rats. Conclusion. DDIT4 is a key player in mediating pyroptosis and IVDD in NPCs through the ROS-TXNIP-NLRP3 axis. Additionally, siDDIT4@G5-P-HA hydrogel has been found to relieve IVDD in rats. Our research offers an innovative treatment option for IVDD. Cite this article: Bone Joint Res 2024;13(5):247–260


Bone & Joint Research
Vol. 13, Issue 12 | Pages 750 - 763
11 Dec 2024
Xie C Gong J Zheng C Zhang J Gao J Tian C Guo X Dai S Gao T

Aims. This meta-analysis and systematic review aimed to comprehensively investigate the effects of vitamin K supplementation on bone mineral density (BMD) at various sites and bone metabolism in middle-aged and older adults. Methods. The databases of PubMed, Web of Science, and Cochrane Library were thoroughly searched from inception to July 2023. Results. The results revealed that vitamin K supplementation increased BMD at the lumbar spine (p = 0.035). Moreover, the pooled effects demonstrated a notable increase in carboxylated osteocalcin (cOC) (p = 0.004), a decrease in uncarboxylated osteocalcin (ucOC) (p < 0.001), and no significant effect on total osteocalcin (tOC) (p = 0.076). Accordingly, the ratio of cOC to ucOC (p = 0.002) significantly increased, while the ratio of ucOC to tOC decreased (p = 0.043). However, there was no significant effect of vitamin K supplementation on other bone metabolism markers, such as cross-linked telopeptide of type 1 collagen (NTx), bone alkaline phosphatase (BAP), and procollagen I N-terminal propeptide (PINP). Subgroup analysis revealed that vitamin K notably enhanced bone health in females by increasing lumbar spine BMD (p = 0.028) and decreasing ucOC (p < 0.001). Vitamin K, especially vitamin K2, exhibited effects on maintaining or increasing lumbar spine BMD, and influencing the balance of cOC and ucOC. Conclusion. This review suggests that the beneficial effects of vitamin K supplementation on bone health primarily involve enhancing the carboxylation of OC rather than altering the total amount of OC. Cite this article: Bone Joint Res 2024;13(12):750–763


Bone & Joint Research
Vol. 12, Issue 11 | Pages 691 - 701
3 Nov 2023
Dai Z Chen Y He E Wang H Guo W Wu Z Huang K Zhao Q

Aims. Osteoporosis is characterized by decreased trabecular bone volume, and microarchitectural deterioration in the medullary cavity. Interleukin-19 (IL-19), a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. The aim of our study was to investigate the effect of IL-19 on osteoporosis. Methods. Blood and femoral bone marrow suspension IL-19 levels were first measured in the lipopolysaccharide (LPS)-induced bone loss model. Small interfering RNA (siRNA) was applied to knock down IL-19 for further validation. Thereafter, osteoclast production was stimulated with IL-19 in combination with mouse macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). The effect of IL-19 was subsequently evaluated using tartrate-resistant acid phosphatase (TRAP) staining and quantitative real-time polymerase chain reaction (RT-qPCR). The effect of IL-19 on osteoprotegerin (OPG) was then assessed using in vitro recombinant IL-19 treatment of primary osteoblasts and MLO-Y4 osteoblast cell line. Finally, transient transfection experiments and chromatin immunoprecipitation (ChIP) experiments were used to examine the exact mechanism of action. Results. In the LPS-induced bone loss mouse model, the levels of IL-19 in peripheral blood serum and femoral bone marrow suspension were significantly increased. The in vivo results indicated that global IL-19 deletion had no significant effect on RANKL content in the serum and bone marrow, but could increase the content of OPG in serum and femoral bone marrow, suggesting that IL-19 inhibits OPG expression in bone marrow mesenchymal stem cells (BMSCs) and thus increases bone resorption. Conclusion. IL-19 promotes bone resorption by suppressing OPG expression in BMSCs in a LPS-induced bone loss mouse model, which highlights the potential benefits and side effects of IL-19 for future clinical applications. Cite this article: Bone Joint Res 2023;12(11):691–701


Bone & Joint Research
Vol. 13, Issue 11 | Pages 682 - 693
26 Nov 2024
Wahl P Heuberger R Pascucci A Imwinkelried T Fürstner M Icken N Schläppi M Pourzal R Gautier E

Aims. Highly cross-linked polyethylene (HXLPE) greatly reduces wear in total hip arthroplasty, compared to conventional polyethylene (CPE). Cross-linking is commonly achieved by irradiation. This study aimed to compare the degree of cross-linking and in vitro wear rates across a cohort of retrieved and unused polyethylene cups/liners from various brands. Methods. Polyethylene acetabular cups/liners were collected at one centre from 1 April 2021 to 30 April 2022. The trans-vinylene index (TVI) and oxidation index (OI) were determined by Fourier-transform infrared spectrometry. Wear was measured using a pin-on-disk test. Results. A total of 47 specimens from ten brands were included. The TVI was independent of time in vivo. A linear correlation (R. 2. = 0.995) was observed between the old and current TVI standards, except for vitamin E-containing polyethylene. The absorbed irradiation dose calculated from the TVI corresponded to product specifications for all but two products. For one electron beam-irradiated HXLPE, a mean dose of 241% (SD 18%) of specifications was determined. For another, gamma-irradiated HXLPE, a mean 41% (SD 13%) of specifications was determined. Lower wear was observed for higher TVI. Conclusion. The TVI is a reliable measure of the absorbed irradiation dose and does not alter over time in vivo. The products of various brands differ by manufacturing details and consequently cross-linking characteristics. Absorption and penetration of electron radiation and gamma radiation differ, potentially leading to higher degrees of cross-linking for electron radiation. There is a non-linear, inverse correlation between TVI and in vitro wear. The wear resistance of the HXLPE with low TVI was reduced and more comparable to CPE. Cite this article: Bone Joint Res 2024;13(11):682–693


Bone & Joint Research
Vol. 13, Issue 6 | Pages 261 - 271
1 Jun 2024
Udomsinprasert W Mookkhan N Tabtimnark T Aramruang T Ungsudechachai T Saengsiwaritt W Jittikoon J Chaikledkaew U Honsawek S

Aims. This study aimed to determine the expression and clinical significance of a cartilage protein, cartilage oligomeric matrix protein (COMP), in knee osteoarthritis (OA) patients. Methods. A total of 270 knee OA patients and 93 healthy controls were recruited. COMP messenger RNA (mRNA) and protein levels in serum, synovial fluid, synovial tissue, and fibroblast-like synoviocytes (FLSs) of knee OA patients were determined using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry. Results. COMP protein levels were significantly elevated in serum and synovial fluid of knee OA patients, especially those in the advanced stages of the disease. Serum COMP was significantly correlated with radiological severity as well as measures of body composition, physical performance, knee pain, and disability. Receiver operating characteristic curve analysis unveiled a diagnostic value of serum COMP as a biomarker of knee OA (41.64 ng/ml, area under the curve (AUC) = 1.00), with a sensitivity of 99.6% and a specificity of 100.0%. Further analysis uncovered that COMP mRNA expression was markedly upregulated in the inflamed synovium of knee OA, consistent with immunohistochemical staining revealing localization of COMP protein in the lining and sub-lining layers of knee OA inflamed synovium. Most notably, relative COMP mRNA expression in knee OA synovium was positively associated with its protein levels in serum and synovial fluid of knee OA patients. In human knee OA FLSs activated with tumour necrosis factor-alpha, COMP mRNA expression was considerably up-regulated in a time-dependent manner. Conclusion. All results indicate that COMP might serve as a supportive diagnostic marker for knee OA in conjunction with the standard diagnostic methods. Cite this article: Bone Joint Res 2024;13(6):261–271


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. Results. Mean callus volume was larger in the elastic fixation group (1,755 mm. 3. (standard error of the mean (SEM) 297)) than in the stiff fixation group (258 mm. 3. (SEM 65)). Pathological observation found that the expression levels of osterix (OSX), collagen, type I, alpha 1 (COL1α1), and alkaline phosphatase (ALP) in the callus of the elastic fixation group were higher than those of the stiff fixation group. The protein sequence of the callus revealed 199 DEPs, 124 of which were highly expressed in the elastic fixation group. In the in vitro study, it was observed that a stress of 200 g led to upregulation of thrombospondin 1 (THBS1) and osteoglycin (OGN) expression in bone marrow mesenchymal stem cells (BMSCs). Additionally, these genes were found to be upregulated during the osteogenic differentiation process of the BMSCs. Conclusion. Elastic fixation can promote fracture healing and osteoblast differentiation in callus, and the ability of elastic fixation to promote osteogenic differentiation of BMSCs may be achieved by upregulating genes such as THBS1 and OGN. Cite this article: Bone Joint Res 2024;13(10):559–572


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1141 - 1149
1 Oct 2024
Saleem J Rawi B Arnander M Pearse E Tennent D

Aims. Extensive literature exists relating to the management of shoulder instability, with a more recent focus on glenoid and humeral bone loss. However, the optimal timing for surgery following a dislocation remains unclear. There is concern that recurrent dislocations may worsen subsequent surgical outcomes, with some advocating stabilization after the first dislocation. The aim of this study was to determine if the recurrence of instability following arthroscopic stabilization in patients without significant glenoid bone loss was influenced by the number of dislocations prior to surgery. Methods. A systematic review and meta-analysis was performed using the PubMed, EMBASE, Orthosearch, and Cochrane databases with the following search terms: ((shoulder or glenohumeral) and (dislocation or subluxation) and arthroscopic and (Bankart or stabilisation or stabilization) and (redislocation or re-dislocation or recurrence or instability)). Methodology followed the PRISMA guidelines. Data and outcomes were synthesized by two independent reviewers, and papers were assessed for bias and quality. Results. Overall, 35 studies including 7,995 shoulders were eligible for analysis, with a mean follow-up of 32.7 months (12 to 159.5). The rate of post-stabilization instability was 9.8% in first-time dislocators, 9.1% in recurrent dislocators, and 8.5% in a mixed cohort. A descriptive analysis investigated the influence of recurrent instability or age in the risk of instability post-stabilization, with an association seen with increasing age and a reduced risk of recurrence post-stabilization. Conclusion. Using modern arthroscopic techniques, patients sustaining an anterior shoulder dislocation without glenoid bone loss can expect a low risk of recurrence postoperatively, and no significant difference was found between first-time and recurrent dislocators. Furthermore, high-risk cohorts can expect a low, albeit slightly higher, rate of redislocation. With the findings of this study, patients and clinicians can be more informed as to the likely outcomes of arthroscopic stabilization within this patient subset. Cite this article: Bone Joint J 2024;106-B(10):1141–1149


Bone & Joint Open
Vol. 4, Issue 5 | Pages 299 - 305
2 May 2023
Shevenell BE Mackenzie J Fisher L McGrory B Babikian G Rana AJ

Aims. Obesity is associated with an increased risk of hip osteoarthritis, resulting in an increased number of total hip arthroplasties (THAs) performed annually. This study examines the peri- and postoperative outcomes of morbidly obese (MO) patients (BMI ≥ 40 kg/m. 2. ) compared to healthy weight (HW) patients (BMI 18.5 to < 25 kg/m. 2. ) who underwent a THA using the anterior-based muscle-sparing (ABMS) approach. Methods. This retrospective cohort study observes peri- and postoperative outcomes of MO and HW patients who underwent a primary, unilateral THA with the ABMS approach. Data from surgeries performed by three surgeons at a single institution was collected from January 2013 to August 2020 and analyzed using Microsoft Excel and Stata 17.0. Results. This study compares 341 MO to 1,140 HW patients. Anaesthesia, surgery duration, and length of hospital stay was significantly lower in HW patients compared to MO. There was no difference in incidence of pulmonary embolism, periprosthetic fracture, or dislocation between the two groups. The rate of infection in MO patients (1.47%) was significantly higher than HW patients (0.14%). Preoperative patient-reported outcome measures (PROMs) show a significantly higher pain level in MO patients and a significantly lower score in functional abilities. Overall, six-week and one-year postoperative data show higher levels of pain, lower levels of functional improvement, and lower satisfaction scores in the MO group. Conclusion. The comorbidities of obesity are well studied; however, the implications of THA using the ABMS approach have not been studied. Our peri- and postoperative results demonstrate significant improvements in PROMs in MO patients undergoing THA. However, the incidence of deep infection was significantly higher in this group compared with HW patients. Cite this article: Bone Jt Open 2023;4(5):299–305


Bone & Joint Research
Vol. 12, Issue 10 | Pages 615 - 623
3 Oct 2023
Helwa-Shalom O Saba F Spitzer E Hanhan S Goren K Markowitz SI Shilo D Khaimov N Gellman YN Deutsch D Blumenfeld A Nevo H Haze A

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. Methods. A reproducible large OCI was created in the right leg femoral trochlea of 93 rats. The OCIs were treated with 0.1, 0.5, 1.0, 2.5, or 5.0 μg/μl recombinant human amelogenin protein (rHAM. +. ) dissolved in propylene glycol alginate (PGA) carrier, or with PGA carrier alone. The degree of healing was evaluated 12 weeks after treatment by morphometric analysis and histological evaluation. Cell recruitment to the site of injury as well as the origin of the migrating cells were assessed four days after treatment with 0.5 μg/μl rHAM. +. using immunohistochemistry and immunofluorescence. Results. A total of 12 weeks after treatment, 0.5 μg/μl rHAM. +. brought about significant repair of the subchondral bone and cartilage. Increased expression of proteoglycan and type II collagen and decreased expression of type I collagen were revealed at the surface of the defect, and an elevated level of type X collagen at the newly developed tide mark region. Conversely, the control group showed osteoarthritic alterations. Recruitment of cells expressing the mesenchymal stem cell (MSC) markers CD105 and STRO-1, from adjacent bone marrow toward the OCI, was noted four days after treatment. Conclusion. We found that 0.5 μg/μl rHAM. +. induced in vivo healing of injured articular cartilage and subchondral bone in a rat model, preventing the destructive post-traumatic osteoarthritic changes seen in control OCIs, through paracrine recruitment of cells a few days after treatment. Cite this article: Bone Joint Res 2023;12(10):615–623


The Bone & Joint Journal
Vol. 106-B, Issue 3 | Pages 277 - 285
1 Mar 2024
Pinto D Hussain S Leo DG Bridgens A Eastwood D Gelfer Y

Aims. Children with spinal dysraphism can develop various musculoskeletal deformities, necessitating a range of orthopaedic interventions, causing significant morbidity, and making considerable demands on resources. This systematic review aimed to identify what outcome measures have been reported in the literature for children with spinal dysraphism who undergo orthopaedic interventions involving the lower limbs. Methods. A PROSPERO-registered systematic literature review was performed following PRISMA guidelines. All relevant studies published until January 2023 were identified. Individual outcomes and outcome measurement tools were extracted verbatim. The measurement tools were assessed for reliability and validity, and all outcomes were grouped according to the Outcome Measures Recommended for use in Randomized Clinical Trials (OMERACT) filters. Results. From 91 eligible studies, 27 individual outcomes were identified, including those related to clinical assessment (n = 12), mobility (n = 4), adverse events (n = 6), investigations (n = 4), and miscellaneous (n = 1). Ten outcome measurement tools were identified, of which Hoffer’s Functional Ambulation Scale was the most commonly used. Several studies used unvalidated measurement tools originally developed for other conditions, and 26 studies developed new measurement tools. On the OMERACT filter, most outcomes reported pathophysiology and/or the impact on life. There were only six patient- or parent-reported outcomes, and none assessed the quality of life. Conclusion. The outcomes that were reported were heterogenous, lack validation and failed to incorporate patient or family perceptions. Until outcomes can be reported unequivocally, research in this area will remain limited. Our findings should guide the development of a core outcome set, which will allow consistency in the reporting of outcomes for this condition. Cite this article: Bone Joint J 2024;106-B(3):277–285


Bone & Joint Research
Vol. 12, Issue 10 | Pages 636 - 643
10 Oct 2023
Hamilton V Sheikh S Szczepanska A Maskell N Hamilton F Reid JP Bzdek BR Murray JRD

Aims. Orthopaedic surgery uses many varied instruments with high-speed, high-impact, thermal energy and sometimes heavy instruments, all of which potentially result in aerosolization of contaminated blood, tissue, and bone, raising concerns for clinicians’ health. This study quantifies the aerosol exposure by measuring the number and size distribution of the particles reaching the lead surgeon during key orthopaedic operations. Methods. The aerosol yield from 17 orthopaedic open surgeries (on the knee, hip, and shoulder) was recorded at the position of the lead surgeon using an Aerodynamic Particle Sizer (APS; 0.5 to 20 μm diameter particles) sampling at 1 s time resolution. Through timestamping, detected aerosol was attributed to specific procedures. Results. Diathermy (electrocautery) and oscillating bone saw use had a high aerosol yield (> 100 particles detected per s) consistent with high exposure to aerosol in the respirable range (< 5 µm) for the lead surgeon. Pulsed lavage, reaming, osteotome use, and jig application/removal were medium aerosol yield (10 to 100 particles s. -1. ). However, pulsed lavage aerosol was largely attributed to the saline jet, osteotome use was always brief, and jig application/removal had a large variability in the associated aerosol yield. Suctioning (with/without saline irrigation) had a low aerosol yield (< 10 particles s. -1. ). Most surprisingly, other high-speed procedures, such as drilling and screwing, had low aerosol yields. Conclusion. This work suggests that additional precautions should be recommended for diathermy and bone sawing, such as enhanced personal protective equipment or the use of suction devices to reduce exposure. Cite this article: Bone Joint Res 2023;12(10):636–643


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1190 - 1196
1 Oct 2024
Gelfer Y McNee AE Harris JD Mavrotas J Deriu L Cashman J Wright J Kothari A

Aims. The aim of this study was to gain a consensus for best practice of the assessment and management of children with idiopathic toe walking (ITW) in order to provide a benchmark for practitioners and guide the best consistent care. Methods. An established Delphi approach with predetermined steps and degree of agreement based on a standardized protocol was used to determine consensus. The steering group members and Delphi survey participants included members from the British Society of Children’s Orthopaedic Surgery (BSCOS) and the Association of Paediatric Chartered Physiotherapists (APCP). The statements included definition, assessment, treatment indications, nonoperative and operative interventions, and outcomes. Descriptive statistics were used for analysis of the Delphi survey results. The AGREE checklist was followed for reporting the results. Results. A total of 227 participants (54% APCP and 46% BSCOS members) completed the first round, and 222 participants (98%) completed the second round. Out of 54 proposed statements included in the first round Delphi, 17 reached ‘consensus in’, no statements reached ‘consensus out’, and 37 reached ‘no consensus’. These 37 statements were then discussed, reworded, amalgamated, or deleted before the second round Delphi of 29 statements. A total of 12 statements reached ‘consensus in’, four ‘consensus out’, and 13 ‘no consensus’. In the final consensus meeting, 13 statements were voted upon. Five were accepted, resulting in a total of 31 approved statements. Conclusion. In the aspects of practice where sufficient evidence is not available, a consensus statement can provide a strong body of opinion that acts as a benchmark for excellence in clinical care. This statement can assist clinicians managing children with ITW to ensure consistent and reliable practice, and reduce geographical variability in practice and outcomes. It will enable those treating ITW to share the published consensus document with both carers and patient groups. Cite this article: Bone Joint J 2024;106-B(10):1190–1196


The Bone & Joint Journal
Vol. 105-B, Issue 10 | Pages 1099 - 1107
1 Oct 2023
Henry JK Shaffrey I Wishman M Palma Munita J Zhu J Cody E Ellis S Deland J Demetracopoulos C

Aims. The Vantage Total Ankle System is a fourth-generation low-profile fixed-bearing implant that has been available since 2016. We aimed to describe our early experience with this implant. Methods. This is a single-centre retrospective review of patients who underwent primary total ankle arthroplasty (TAA) with a Vantage implant between November 2017 and February 2020, with a minimum of two years’ follow-up. Four surgeons contributed patients. The primary outcome was reoperation and revision rate of the Vantage implant at two years. Secondary outcomes included radiological alignment, peri-implant complications, and pre- and postoperative patient-reported outcomes. Results. There were 168 patients (171 ankles) included with a mean follow-up of 2.81 years (2 to 4.6) and mean age of 63.0 years (SD 9.4). Of the ten ankles with implant failure (5.8%), six had loosening of the tibial component. In the remaining four failed implants, one was due to periprosthetic joint infection (PJI), one was due to loosening of the talar component, and two were due to loosening of both the tibial and talar components. Seven patients underwent reoperation: irrigation and debridement for superficial infection (n = 4); bone grafting for cysts (n = 2); and open reduction internal fixation (n = 1). Asymptomatic peri-implant lucency/subsidence occurred in 20.1% of ankles, with the majority involving the tibial component (n = 25). There were statistically significant improvements in PROMs in all domains. Conclusion. Short-term results of this implant demonstrate early survival comparable to the reported survivorship of similar low-profile, non-stemmed implants. Radiological lucency occurred more commonly at the tibial component, and revisions occurred primarily due to loosening of the tibial component. Further research is needed to evaluate longer-term survivorship. Cite this article: Bone Joint J 2023;105-B(10):1099–1107


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. Results. LASSO regression analysis selected possible risk factors for SSI, including age, diabetes, operating time, skin graft or flap, resected tumour size, smoking, and radiation therapy. Multivariate analysis revealed that age, diabetes, smoking during the previous year, operating time, and radiation therapy were independent risk factors for SSI. A nomogram was developed based on the results of multivariate logistic regression analysis. In the development cohort, the incidence of SSI was 4.5% in the low-risk group (risk score < 6.89) and 26.6% in the high-risk group (risk score ≥ 6.89; p < 0.001). In the validation cohort, the incidence of SSI was 2.0% in the low-risk group and 15.9% in the high-risk group (p = 0.004). Conclusion. Our nomogram will enable surgeons to assess the risk of SSI in patients with STS. In patients with high risk of SSI, frequent monitoring and aggressive interventions should be considered to prevent this. Cite this article: Bone Joint J 2024;106-B(5):492–500


Bone & Joint Research
Vol. 13, Issue 3 | Pages 101 - 109
4 Mar 2024
Higashihira S Simpson SJ Morita A Suryavanshi JR Arnold CJ Natoli RM Greenfield EM

Aims. Biofilm infections are among the most challenging complications in orthopaedics, as bacteria within the biofilms are protected from the host immune system and many antibiotics. Halicin exhibits broad-spectrum activity against many planktonic bacteria, and previous studies have demonstrated that halicin is also effective against Staphylococcus aureus biofilms grown on polystyrene or polypropylene substrates. However, the effectiveness of many antibiotics can be substantially altered depending on which orthopaedically relevant substrates the biofilms grow. This study, therefore, evaluated the activity of halicin against less mature and more mature S. aureus biofilms grown on titanium alloy, cobalt-chrome, ultra-high molecular weight polyethylene (UHMWPE), devitalized muscle, or devitalized bone. Methods. S. aureus-Xen36 biofilms were grown on the various substrates for 24 hours or seven days. Biofilms were incubated with various concentrations of halicin or vancomycin and then allowed to recover without antibiotics. Minimal biofilm eradication concentrations (MBECs) were defined by CFU counting and resazurin reduction assays, and were compared with the planktonic minimal inhibitory concentrations (MICs). Results. Halicin continued to exert significantly (p < 0.01) more antibacterial activity against biofilms grown on all tested orthopaedically relevant substrates than vancomycin, an antibiotic known to be affected by biofilm maturity. For example, halicin MBECs against both less mature and more mature biofilms were ten-fold to 40-fold higher than its MIC. In contrast, vancomycin MBECs against the less mature biofilms were 50-fold to 200-fold higher than its MIC, and 100-fold to 400-fold higher against the more mature biofilms. Conclusion. Halicin is a promising antibiotic that should be tested in animal models of orthopaedic infection. Cite this article: Bone Joint Res 2024;13(3):101–109


Bone & Joint Open
Vol. 4, Issue 11 | Pages 873 - 880
17 Nov 2023
Swaby L Perry DC Walker K Hind D Mills A Jayasuriya R Totton N Desoysa L Chatters R Young B Sherratt F Latimer N Keetharuth A Kenison L Walters S Gardner A Ahuja S Campbell L Greenwood S Cole A

Aims. Scoliosis is a lateral curvature of the spine with associated rotation, often causing distress due to appearance. For some curves, there is good evidence to support the use of a spinal brace, worn for 20 to 24 hours a day to minimize the curve, making it as straight as possible during growth, preventing progression. Compliance can be poor due to appearance and comfort. A night-time brace, worn for eight to 12 hours, can achieve higher levels of curve correction while patients are supine, and could be preferable for patients, but evidence of efficacy is limited. This is the protocol for a randomized controlled trial of ‘full-time bracing’ versus ‘night-time bracing’ in adolescent idiopathic scoliosis (AIS). Methods. UK paediatric spine clinics will recruit 780 participants aged ten to 15 years-old with AIS, Risser stage 0, 1, or 2, and curve size (Cobb angle) 20° to 40° with apex at or below T7. Patients are randomly allocated 1:1, to either full-time or night-time bracing. A qualitative sub-study will explore communication and experiences of families in terms of bracing and research. Patient and Public Involvement & Engagement informed study design and will assist with aspects of trial delivery and dissemination. Discussion. The primary outcome is ‘treatment failure’ (Cobb angle progression to 50° or more before skeletal maturity); skeletal maturity is at Risser stage 4 in females and 5 in males, or ‘treatment success’ (Cobb angle less than 50° at skeletal maturity). The comparison is on a non-inferiority basis (non-inferiority margin 11%). Participants are followed up every six months while in brace, and at one and two years after skeletal maturity. Secondary outcomes include the Scoliosis Research Society 22 questionnaire and measures of quality of life, psychological effects of bracing, adherence, anxiety and depression, sleep, satisfaction, and educational attainment. All data will be collected through the British Spine Registry. Cite this article: Bone Jt Open 2023;4(11):873–880