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Bone & Joint Open
Vol. 3, Issue 11 | Pages 877 - 884
14 Nov 2022
Archer H Reine S Alshaikhsalama A Wells J Kohli A Vazquez L Hummer A DiFranco MD Ljuhar R Xi Y Chhabra A

Aims

Hip dysplasia (HD) leads to premature osteoarthritis. Timely detection and correction of HD has been shown to improve pain, functional status, and hip longevity. Several time-consuming radiological measurements are currently used to confirm HD. An artificial intelligence (AI) software named HIPPO automatically locates anatomical landmarks on anteroposterior pelvis radiographs and performs the needed measurements. The primary aim of this study was to assess the reliability of this tool as compared to multi-reader evaluation in clinically proven cases of adult HD. The secondary aims were to assess the time savings achieved and evaluate inter-reader assessment.

Methods

A consecutive preoperative sample of 130 HD patients (256 hips) was used. This cohort included 82.3% females (n = 107) and 17.7% males (n = 23) with median patient age of 28.6 years (interquartile range (IQR) 22.5 to 37.2). Three trained readers’ measurements were compared to AI outputs of lateral centre-edge angle (LCEA), caput-collum-diaphyseal (CCD) angle, pelvic obliquity, Tönnis angle, Sharp’s angle, and femoral head coverage. Intraclass correlation coefficients (ICC) and Bland-Altman analyses were obtained.


Bone & Joint Open
Vol. 5, Issue 3 | Pages 154 - 161
1 Mar 2024
Homma Y Zhuang X Watari T Hayashi K Baba T Kamath A Ishijima M

Aims. It is important to analyze objectively the hammering sound in cup press-fit technique in total hip arthroplasty (THA) in order to better understand the change of the sound during impaction. We hypothesized that a specific characteristic would present in a hammering sound with successful fixation. We designed the study to quantitatively investigate the acoustic characteristics during cementless cup impaction in THA. Methods. In 52 THAs performed between November 2018 and April 2022, the acoustic parameters of the hammering sound of 224 impacts of successful press-fit fixation, and 55 impacts of unsuccessful press-fit fixation, were analyzed. The successful fixation was defined if the following two criteria were met: 1) intraoperatively, the stability of the cup was retained after manual application of the torque test; and 2) at one month postoperatively, the cup showed no translation on radiograph. Each hammering sound was converted to sound pressures in 24 frequency bands by fast Fourier transform analysis. Basic patient characteristics were assessed as potential contributors to the hammering sound. Results. The median sound pressure (SP) of successful fixation at 0.5 to 1.0 kHz was higher than that of unsuccessful fixation (0.0694 (interquartile range (IQR) 0.04721 to 0.09576) vs 0.05425 (IQR 0.03047 to 0.06803), p < 0.001). The median SP of successful fixation at 3.5 to 4.0 kHz and 4.0 to 4.5 kHz was lower than that of unsuccessful fixation (0.0812 (IQR 0.05631 to 0.01161) vs 0.1233 (IQR 0.0730 to 0.1449), p < 0.001; and 0.0891 (IQR 0.0526 to 0.0891) vs 0.0885 (IQR 0.0716 to 0.1048); p < 0.001, respectively). There was a statistically significant positive relationship between body weight and SP at 0.5 to 1.0 kHz (p < 0.001). Multivariate analyses indicated that the SP at 0.5 to 1.0 kHz and 3.5 to 4.0 kHz was independently associated with the successful fixation. Conclusion. The frequency bands of 0.5 to 1.0 and 3.5 to 4.0 kHz were the key to distinguish the sound characteristics between successful and unsuccessful press-fit cup fixation. Cite this article: Bone Jt Open 2024;5(3):154–161


Bone & Joint Open
Vol. 4, Issue 3 | Pages 154 - 161
28 Mar 2023
Homma Y Zhuang X Watari T Hayashi K Baba T Kamath A Ishijima M

Aims. It is important to analyze objectively the hammering sound in cup press-fit technique in total hip arthroplasty (THA) in order to better understand the change of the sound during impaction. We hypothesized that a specific characteristic would present in a hammering sound with successful fixation. We designed the study to quantitatively investigate the acoustic characteristics during cementless cup impaction in THA. Methods. In 52 THAs performed between November 2018 and April 2022, the acoustic parameters of the hammering sound of 224 impacts of successful press-fit fixation, and 55 impacts of unsuccessful press-fit fixation, were analyzed. The successful fixation was defined if the following two criteria were met: 1) intraoperatively, the stability of the cup was retained after manual application of the torque test; and 2) at one month postoperatively, the cup showed no translation on radiograph. Each hammering sound was converted to sound pressures in 24 frequency bands by fast Fourier transform analysis. Basic patient characteristics were assessed as potential contributors to the hammering sound. Results. The median sound pressure (SP) of successful fixation at 0.5 to 1.0 kHz was higher than that of unsuccessful fixation (0.0694 (interquartile range (IQR) 0.04721 to 0.09576) vs 0.05425 (IQR 0.03047 to 0.06803), p < 0.001). The median SP of successful fixation at 3.5 to 4.0 kHz and 4.0 to 4.5 kHz was lower than that of unsuccessful fixation (0.0812 (IQR 0.05631 to 0.01161) vs 0.1233 (IQR 0.0730 to 0.1449), p < 0.001; and 0.0891 (IQR 0.0526 to 0.0891) vs 0.0885 (IQR 0.0716 to 0.1048); p < 0.001, respectively). There was a statistically significant positive relationship between body weight and SP at 0.5 to 1.0 kHz (p < 0.001). Multivariate analyses indicated that the SP at 0.5 to 1.0 kHz and 3.5 to 4.0 kHz was independently associated with the successful fixation. Conclusion. The frequency bands of 0.5 to 1.0 and 3.5 to 4.0 kHz were the key to distinguish the sound characteristics between successful and unsuccessful press-fit cup fixation. Cite this article: Bone Jt Open 2024;4(3):154–161


The Bone & Joint Journal
Vol. 97-B, Issue 10_Supple_A | Pages 40 - 44
1 Oct 2015
Thienpont E Lavand'homme P Kehlet H

Total knee arthroplasty (TKA) is a major orthopaedic intervention. The length of a patient's stay has been progressively reduced with the introduction of enhanced recovery protocols: day-case surgery has become the ultimate challenge.

This narrative review shows the potential limitations of day-case TKA. These constraints may be social, linked to patient’s comorbidities, or due to surgery-related adverse events (e.g. pain, post-operative nausea and vomiting, etc.).

Using patient stratification, tailored surgical techniques and multimodal opioid-sparing analgesia, day-case TKA might be achievable in a limited group of patients. The younger, male patient without comorbidities and with an excellent social network around him might be a candidate.

Demographic changes, effective recovery programmes and less invasive surgical techniques such as unicondylar knee arthroplasty, may increase the size of the group of potential day-case patients.

The cost reduction achieved by day-case TKA needs to be balanced against any increase in morbidity and mortality and the cost of advanced follow-up at a distance with new technology. These factors need to be evaluated before adopting this ultimate ‘fast-track’ approach.

Cite this article: Bone Joint J 2015;97-B(10 Suppl A):40–4.


Bone & Joint Open
Vol. 4, Issue 6 | Pages 457 - 462
26 Jun 2023
Bredgaard Jensen C Gromov K Petersen PB Jørgensen CC Kehlet H Troelsen A

Aims

Medial unicompartmental knee arthroplasty (mUKA) is an advised treatment for anteromedial knee osteoarthritis. While long-term survival after mUKA is well described, reported incidences of short-term surgical complications vary and the effect of surgical usage on complications is less established. We aimed to describe the overall occurrence and treatment of surgical complications within 90 days of mUKA, as well as occurrence in high-usage centres compared to low-usage centres.

Methods

mUKAs performed in eight fast-track centres from February 2010 to June 2018 were included from the Lundbeck Foundation Centre for Fast-track Hip and Knee Replacement Database. All readmissions within 90 days of surgery underwent chart review and readmissions related to the surgical wound or the prosthesis were recorded. Centres were categorized as high-usage centres when using mUKA in ≥ 20% of annual knee arthroplasties. The occurrence of complications between high- and low-usage centres were compared using Fisher’s exact test.


The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 573 - 581
1 Jun 2024
van Houtert WFC Strijbos DO Bimmel R Krijnen WP Jager J van Meeteren NLU van der Sluis G

Aims

To investigate the impact of consecutive perioperative care transitions on in-hospital recovery of patients who had primary total knee arthroplasty (TKA) over an 11-year period.

Methods

This observational cohort study used electronic health record data from all patients undergoing preoperative screening for primary TKA at a Northern Netherlands hospital between 2009 and 2020. In this timeframe, three perioperative care transitions were divided into four periods: Baseline care (Joint Care, n = 171; May 2009 to August 2010), Function-tailored (n = 404; September 2010 to October 2013), Fast-track (n = 721; November 2013 to May 2018), and Prehabilitation (n = 601; June 2018 to December 2020). In-hospital recovery was measured using inpatient recovery of activities (IROA), length of stay (LOS), and discharge to preoperative living situation (PLS). Multivariable regression models were used to analyze the impact of each perioperative care transition on in-hospital recovery.


The Bone & Joint Journal
Vol. 106-B, Issue 4 | Pages 303 - 306
1 Apr 2024
Staats K Kayani B Haddad FS


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1100 - 1110
1 Oct 2024
Arenas-Miquelez A Barco R Cabo Cabo FJ Hachem A

Bone defects are frequently observed in anterior shoulder instability. Over the last decade, knowledge of the association of bone loss with increased failure rates of soft-tissue repair has shifted the surgical management of chronic shoulder instability. On the glenoid side, there is no controversy about the critical glenoid bone loss being 20%. However, poor outcomes have been described even with a subcritical glenoid bone defect as low as 13.5%. On the humeral side, the Hill-Sachs lesion should be evaluated concomitantly with the glenoid defect as the two sides of the same bipolar lesion which interact in the instability process, as described by the glenoid track concept. We advocate adding remplissage to every Bankart repair in patients with a Hill-Sachs lesion, regardless of the glenoid bone loss. When critical or subcritical glenoid bone loss occurs in active patients (> 15%) or bipolar off-track lesions, we should consider anterior glenoid bone reconstructions. The techniques have evolved significantly over the last two decades, moving from open procedures to arthroscopic, and from screw fixation to metal-free fixation. The new arthroscopic techniques of glenoid bone reconstruction procedures allow precise positioning of the graft, identification, and treatment of concomitant injuries with low morbidity and faster recovery. Given the problems associated with bone resorption and metal hardware protrusion, the new metal-free techniques for Latarjet or free bone block procedures seem a good solution to avoid these complications, although no long-term data are yet available. Cite this article: Bone Joint J 2024;106-B(10):1100–1110


Bone & Joint Research
Vol. 13, Issue 1 | Pages 4 - 18
2 Jan 2024
Wang Y Wu Z Yan G Li S Zhang Y Li G Wu C

Aims. cAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect. Methods. CREB1 activity and expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) in cells and tissues were measured by immunoblotting and immunohistochemical (IHC) staining. The effect of 666-15 on chondrocyte viability and apoptosis was examined by cell counting kit-8 (CCK-8) assay, JC-10, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. The effect of 666-15 on the microstructure of subchondral bone, and the synthesis and catabolism of cartilage, in anterior cruciate ligament transection mice were detected by micro-CT, safranin O and fast green (S/F), immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA). Results. CREB1 was hyperactive in osteoarthritic articular cartilage, interleukin (IL)-1β-treated cartilage explants, and IL-1β- or carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-treated chondrocytes. 666-15 enhanced cell viability of OA-like chondrocytes and alleviated IL-1β- or CCCP-induced chondrocyte injury through inhibition of mitochondrial dysfunction-associated apoptosis. Moreover, inhibition of CREB1 by 666-15 suppressed expression of ADAMTS4. Additionally, 666-15 alleviated joint degeneration in an ACLT mouse model. Conclusion. Hyperactive CREB1 played a critical role in OA development, and 666-15 exerted anti-IL-1β or anti-CCCP effects in vitro as well as joint-protective effects in vivo. 666-15 may therefore be used as a promising anti-OA drug. Cite this article: Bone Joint Res 2024;13(1):4–18


Bone & Joint Research
Vol. 12, Issue 2 | Pages 121 - 132
1 Feb 2023
Mo H Wang Z He Z Wan J Lu R Wang C Chen A Cheng P

Aims. Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA. Methods. After inhibiting Peli1 expression in chondrocytes with small interfering RNA (siRNA), interleukin (IL)-1β was used to simulate inflammation, and OA-related indicators such as synthesis, decomposition, inflammation, and apoptosis were detected. Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signalling pathway were detected. After inhibiting the expression of Peli1 in macrophages Raw 264.7 with siRNA and intervening with lipopolysaccharide (LPS), the polarization index of macrophages was detected, and the supernatant of macrophage medium was extracted as conditioned medium to act on chondrocytes and detect the apoptosis index. The OA model of mice was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity to reduce the expression of Peli1. The degree of cartilage destruction and synovitis were evaluated by haematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and immunohistochemistry. Results. In chondrocytes, knockdown of Peli1 produced anti-inflammatory and anti-apoptotic effects by targeting the TLR and NF-κB signalling pathways. We found that in macrophages, knockdown of Peli1 can inhibit M1-type polarization of macrophages. In addition, the corresponding conditioned culture medium of macrophages applied to chondrocytes can also produce an anti-apoptotic effect. During in vivo experiments, the results have also shown that knockdown Peli1 reduces cartilage destruction and synovial inflammation. Conclusion. Knockdown of Peli1 has a therapeutic effect on OA, which therefore makes it a potential therapeutic target for OA. Cite this article: Bone Joint Res 2023;12(2):121–132


Bone & Joint Research
Vol. 13, Issue 11 | Pages 659 - 672
20 Nov 2024
Mo H Sun K Hou Y Ruan Z He Z Liu H Li L Wang Z Guo F

Aims. Osteoarthritis (OA) is a common degenerative disease. PA28γ is a member of the 11S proteasome activator and is involved in the regulation of several important cellular processes, including cell proliferation, apoptosis, and inflammation. This study aimed to explore the role of PA28γ in the occurrence and development of OA and its potential mechanism. Methods. A total of 120 newborn male mice were employed for the isolation and culture of primary chondrocytes. OA-related indicators such as anabolism, catabolism, inflammation, and apoptosis were detected. Effects and related mechanisms of PA28γ in chondrocyte endoplasmic reticulum (ER) stress were studied using western blotting, real-time polymerase chain reaction (PCR), and immunofluorescence. The OA mouse model was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity of 15 12-week-old male mice to reduce the expression of PA28γ. The degree of cartilage destruction was evaluated by haematoxylin and eosin (HE) staining, safranin O/fast green staining, toluidine blue staining, and immunohistochemistry. Results. We found that PA28γ knockdown in chondrocytes can effectively improve anabolism and catabolism and inhibit inflammation, apoptosis, and ER stress. Moreover, PA28γ knockdown affected the phosphorylation of IRE1α and the expression of TRAF2, thereby affecting the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signalling pathways, and finally affecting the inflammatory response of chondrocytes. In addition, we found that PA28γ knockdown can promote the phosphorylation of signal transducer and activator of transcription 3 (STAT3), thereby inhibiting ER stress in chondrocytes. The use of Stattic (an inhibitor of STAT3 phosphorylation) enhanced ER stress. In vivo, we found that PA28γ knockdown effectively reduced cartilage destruction in a mouse model of OA induced by the DMM surgery. Conclusion. PA28γ knockdown in chondrocytes can inhibit anabolic and catabolic dysregulation, inflammatory response, and apoptosis in OA. Moreover, PA28γ knockdown in chondrocytes can inhibit ER stress by promoting STAT3 phosphorylation. Cite this article: Bone Joint Res 2024;13(11):659–672


Bone & Joint Research
Vol. 9, Issue 7 | Pages 429 - 439
1 Jul 2020
Tahir M Chaudhry EA Zaffar Z Anwar K Mamoon MAH Ahmad M Jamali AR Mehboob G

Aims. We hypothesized that the wide-awake local anaesthesia with no tourniquet (WALANT) technique is cost-effective, easy to use, safe, and reproducible, with a low learning curve towards mastery, having a high patient satisfaction rate. Furthermore, WALANT would be a suitable alternative for the austere and developing nation environments where lack of funds and resources are a common issue. Methods. This was a randomized control trial of 169 patients who required surgery for closed isolated distal radius fractures. The study was performed between March 2016 and April 2019 at a public sector level 1 trauma centre. General anaesthesia was used in 56 patients, Bier’s block in 58 patients, and WALANT in 55 patients. Data were collected on pre-, peri-, and postoperative parameters, clinical outcome, hospital costs, and patient satisfaction. One-way analysis of variance (ANOVA) was used with a p-value of 0.05 being significant. Results. Operations with WALANT proceeded sooner, and patients recovered faster, resulting in mean fewer missed working days (7.8 (SD 1.67)) compared with general anaesthesia (20.1 (SD 7.37)) or Bier’s block (14.1 (SD 7.65)) (p < 0.001). The WALANT patients did not develop complications, while the other patients did (p < 0.04). Clinical outcomes did not differ, nor did surgeon qualification affect clinical outcomes. Mean hospital costs were lower for WALANT ($428.50 (SD 77.71)) than for general anaesthesia ($630.63 (SD 114.77)) or Bier’s block ($734.00 (SD 37.54)) (p < 0.001). Patient satisfaction was also higher (p < 0.001). Conclusion. WALANT for distal radius fractures results in a faster recovery, is more cost-effective, has similar clinical outcomes, and has fewer complications than general anaesthesia or Bier's block. This makes WALANT an attractive technique in any setting, but especially in middle- and low-income countries. Cite this article: Bone Joint Res 2020;9(7):429–439


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 × 10. 9. 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. Results. Significantly higher content of DNA and collagen was observed for the pEV-treated group compared to control and cEV groups. No differences were found in GAG quantification nor in EVs uptake within any treated group. Conclusion. In conclusion, pEVs showed better performance than cEVs in our in vitro OA model. Although further studies are needed, pEVs are shown as a potential alternative to cEVs for cell-free regenerative medicine. Cite this article: Bone Joint Res 2023;12(10):667–676


Bone & Joint Research
Vol. 10, Issue 11 | Pages 723 - 733
1 Nov 2021
Garner AJ Dandridge OW Amis AA Cobb JP van Arkel RJ

Aims. Bi-unicondylar arthroplasty (Bi-UKA) is a bone and anterior cruciate ligament (ACL)-preserving alternative to total knee arthroplasty (TKA) when the patellofemoral joint is preserved. The aim of this study is to investigate the clinical outcomes and biomechanics of Bi-UKA. Methods. Bi-UKA subjects (n = 22) were measured on an instrumented treadmill, using standard gait metrics, at top walking speeds. Age-, sex-, and BMI-matched healthy (n = 24) and primary TKA (n = 22) subjects formed control groups. TKA subjects with preoperative patellofemoral or tricompartmental arthritis or ACL dysfunction were excluded. The Oxford Knee Score (OKS) and EuroQol five-dimension questionnaire (EQ-5D) were compared. Bi-UKA, then TKA, were performed on eight fresh frozen cadaveric knees, to investigate knee extensor efficiency under controlled laboratory conditions, using a repeated measures study design. Results. Bi-UKA walked 20% faster than TKA (Bi-UKA mean top walking speed 6.7 km/h (SD 0.9),TKA 5.6 km/h (SD 0.7), p < 0.001), exhibiting nearer-normal vertical ground reaction forces in maximum weight acceptance and mid-stance, with longer step and stride lengths compared to TKA (p < 0.048). Bi-UKA subjects reported higher OKS (p = 0.004) and EQ-5D (p < 0.001). In vitro, Bi-UKA generated the same extensor moment as native knees at low flexion angles, while reduced extensor moment was measured following TKA (p < 0.003). Conversely, at higher flexion angles, the extensor moment of TKA was normal. Over the full range, the extensor mechanism was more efficient following Bi-UKA than TKA (p < 0.028). Conclusion. Bi-UKA had more normal gait characteristics and improved patient-reported outcomes, compared to matched TKA subjects. This can, in part, be explained by differences in extensor efficiency. Cite this article: Bone Joint Res 2021;10(11):723–733


Bone & Joint Research
Vol. 10, Issue 8 | Pages 548 - 557
25 Aug 2021
Tao Z Zhou Y Zeng B Yang X Su M

Aims. MicroRNA-183 (miR-183) is known to play important roles in osteoarthritis (OA) pain. The aims of this study were to explore the specific functions of miR-183 in OA pain and to investigate the underlying mechanisms. Methods. Clinical samples were collected from patients with OA, and a mouse model of OA pain was constructed by surgically induced destabilization of the medial meniscus (DMM). Reverse transcription quantitative polymerase chain reaction was employed to measure the expression of miR-183, transforming growth factor α (TGFα), C-C motif chemokine ligand 2 (CCL2), proinflammatory cytokines (interleukin (IL)-6, IL-1β, and tumour necrosis factor-α (TNF-α)), and pain-related factors (transient receptor potential vanilloid subtype-1 (TRPV1), voltage-gated sodium 1.3, 1.7, and 1.8 (Nav1.3, Nav1.7, and Nav1.8)). Expression of miR-183 in the dorsal root ganglia (DRG) of mice was evaluated by in situ hybridization. TGFα, CCL2, and C-C chemokine receptor type 2 (CCR2) levels were examined by immunoblot analysis and interaction between miR-183 and TGFα, determined by luciferase reporter assay. The extent of pain in mice was measured using a behavioural assay, and OA severity assessed by Safranin O and Fast Green staining. Immunofluorescent staining was conducted to examine the infiltration of macrophages in mouse DRG. Results. miR-183 was downregulated in tissue samples from patients and mice with OA. In DMM mice, overexpression of miR-183 inhibited the expression of proinflammatory cytokines (IL-6, IL-1β, TNF-α) and pain-related factors (TRPV1, Nav1.3, Nav1.7, Nav1.8) in DRG. OA pain was relieved by miR-183-mediated inhibition of macrophage infiltration, and dual luciferase reporter assay demonstrated that miR-183 directly targeted TGFα. Conclusion. Our data demonstrate that miR-183 can ameliorate OA pain by inhibiting the TGFα-CCL2/CCR2 signalling axis, providing an excellent therapeutic target for OA treatment. Cite this article: Bone Joint Res 2021;10(8):548–557


Bone & Joint Open
Vol. 2, Issue 12 | Pages 1089 - 1095
21 Dec 2021
Luo W Ali MS Limb R Cornforth C Perry DC

Aims. The Patient-Reported Outcomes Measurement Information System (PROMIS) has demonstrated faster administration, lower burden of data capture and reduced floor and ceiling effects compared to traditional Patient Reported Outcomes Measurements (PROMs). We investigated the suitability of PROMIS Mobility score in assessing physical function in the sequelae of childhood hip disease. Methods. In all, 266 adolscents (aged ≥ 12 years) and adults were identified with a prior diagnosis of childhood hip disease (either Perthes’ disease (n = 232 (87.2%)) or Slipped Capital Femoral Epiphysis (n = 34 (12.8%)) with a mean age of 27.73 years (SD 12.24). Participants completed the PROMIS Mobility Computer Adaptive Test, the Non-Arthritic Hip Score (NAHS), EuroQol five-dimension five-level questionnaire, and the Numeric Pain Rating Scale. We investigated the correlation between the PROMIS Mobility and other tools to assess use in this population and any clustering of outcome scores. Results. There was a strong correlation between the PROMIS Mobility and other established PROMs; NAHS (rs = 0.79; p < 0.001). There was notable clustering in PROMIS at the upper end of the distribution score (42.5%), with less seen in the NAHS (20.3%). However, the clustering was broadly similar between PROMIS Mobility and the comparable domains of the NAHS; function (53.6%), and activity (35.0%). Conclusion. PROMIS Mobility strongly correlated with other tools demonstrating convergent construct validity. There was clustering of physical function scores at the upper end of the distributions, which may reflect truncation of the data caused by participants having excellent outcomes. There were elements of disease not captured within PROMIS Mobility alone, and difficulties in differentiating those with the highest levels of function. Cite this article: Bone Jt Open 2021;2(12):1089–1095


Aims. This study aimed to investigate whether human umbilical cord mesenchymal stem cells (UC-MSCs) can prevent articular cartilage degradation and explore the underlying mechanisms in a rat osteoarthritis (OA) model induced by monosodium iodoacetate (MIA). Methods. Human UC-MSCs were characterized by their phenotype and multilineage differentiation potential. Two weeks after MIA induction in rats, human UC-MSCs were intra-articularly injected once a week for three weeks. The therapeutic effect of human UC-MSCs was evaluated by haematoxylin and eosin, toluidine blue, Safranin-O/Fast green staining, and Mankin scores. Markers of joint cartilage injury and pro- and anti-inflammatory markers were detected by immunohistochemistry. Results. Histopathological analysis showed that intra-articular injection of human UC-MSCs significantly inhibited the progression of OA, as demonstrated by reduced cartilage degradation, increased Safranin-O staining, and lower Mankin scores. Immunohistochemistry showed that human UC-MSC treatment down-regulated the expression of matrix metalloproteinase-13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), and enhanced the expression of type II collagen and ki67 in the articular cartilage. Furthermore, human UC-MSCs significantly decreased the expression of interleukin (IL)-1β and tumour necrosis factor-α (TNF-α), while increasing TNF-α-induced protein 6 and IL-1 receptor antagonist. Conclusion. Our results demonstrated that human UC-MSCs ameliorate MIA-induced OA by preventing cartilage degradation, restoring the proliferation of chondrocytes, and inhibiting the inflammatory response, which implies that human UC-MSCs may be a promising strategy for the treatment of OA. Cite this article: Bone Joint Res 2021;10(3):226–236


Bone & Joint Research
Vol. 9, Issue 10 | Pages 731 - 741
28 Oct 2020
He Z Nie P Lu J Ling Y Guo J Zhang B Hu J Liao J Gu J Dai B Feng Z

Aims. Osteoarthritis (OA) is a disabling joint disorder and mechanical loading is an important pathogenesis. This study aims to investigate the benefits of less mechanical loading created by intermittent tail suspension for knee OA. Methods. A post-traumatic OA model was established in 20 rats (12 weeks old, male). Ten rats were treated with less mechanical loading through intermittent tail suspension, while another ten rats were treated with normal mechanical loading. Cartilage damage was determined by gross appearance, Safranin O/Fast Green staining, and immunohistochemistry examinations. Subchondral bone changes were analyzed by micro-CT and tartrate-resistant acid phosphatase (TRAP) staining, and serum inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA). Results. Our radiographs showed that joint space was significantly enlarged in rats with less mechanical loading. Moreover, cartilage destruction was attenuated in the less mechanical loading group with lower histological damage scores, and lower expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, matrix metalloproteinase (MMP)-3, and MMP-13. In addition, subchondral bone abnormal changes were ameliorated in OA rats with less mechanical loading, as reduced bone mineral density (BMD), bone volume/tissue volume (BV/TV), and number of osteophytes and osteoclasts in the subchondral bone were observed. Finally, the level of serum inflammatory cytokines was significantly downregulated in the less mechanical loading group compared with the normal mechanical loading group, as well as the expression of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), caspase-1, and interleukin 1β (IL-1β) in the cartilage. Conclusion. Less mechanical loading alleviates cartilage destruction, subchondral bone changes, and secondary inflammation in OA joints. This study provides fundamental insights into the benefit of non-weight loading rest for patients with OA. Cite this article: Bone Joint Res 2020;9(10):731–741


Bone & Joint Research
Vol. 5, Issue 7 | Pages 287 - 293
1 Jul 2016
Ismail H Phedy P Kholinne E Djaja YP Kusnadi Y Merlina M Yulisa ND

Objectives. To explore the therapeutic potential of combining bone marrow-derived mesenchymal stem cells (BM-MSCs) and hydroxyapatite (HA) granules to treat nonunion of the long bone. Methods. Ten patients with an atrophic nonunion of a long bone fracture were selectively divided into two groups. Five subjects in the treatment group were treated with the combination of 15 million autologous BM-MSCs, 5g/cm. 3. (HA) granules and internal fixation. Control subjects were treated with iliac crest autograft, 5g/cm. 3. HA granules and internal fixation. The outcomes measured were post-operative pain (visual analogue scale), level of functionality (LEFS and DASH), and radiograph assessment. Results. Post-operative pain evaluation showed no significant differences between the two groups. The treatment group demonstrated faster initial radiographic and functional improvements. Statistically significant differences in functional scores were present during the first (p = 0.002), second (p = 0.005) and third (p = 0.01) month. Both groups achieved similar outcomes by the end of one-year follow-up. No immunologic or neoplastic side effects were reported. Conclusions. All cases of nonunion of a long bone presented in this study were successfully treated using autologous BM-MSCs. The combination of autologous BM-MSCs and HA granules is a safe method for treating nonunion. Patients treated with BM-MSCs had faster initial radiographic and functional improvements. By the end of 12 months, both groups had similar outcomes. Cite this article: H.D. Ismail, P. Phedy, E. Kholinne, Y. P. Djaja, Y. Kusnadi, M. Merlina, N. D. Yulisa. Mesenchymal stem cell implantation in atrophic nonunion of the long bones: A translational study. Bone Joint Res 2016;5:287–293. DOI: 10.1302/2046-3758.57.2000587


Bone & Joint Research
Vol. 9, Issue 3 | Pages 108 - 119
1 Mar 2020
Akhbari P Karamchandani U Jaggard MKJ Graça G Bhattacharya R Lindon JC Williams HRT Gupte CM

Aims. Metabolic profiling is a top-down method of analysis looking at metabolites, which are the intermediate or end products of various cellular pathways. Our primary objective was to perform a systematic review of the published literature to identify metabolites in human synovial fluid (HSF), which have been categorized by metabolic profiling techniques. A secondary objective was to identify any metabolites that may represent potential biomarkers of orthopaedic disease processes. Methods. A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines using the MEDLINE, Embase, PubMed, and Cochrane databases. Studies included were case series, case control series, and cohort studies looking specifically at HSF. Results. The primary analysis, which pooled the results from 17 published studies and four meeting abstracts, identified over 200 metabolites. Seven of these studies (six published studies, one meeting abstract) had asymptomatic control groups and collectively suggested 26 putative biomarkers in osteoarthritis, inflammatory arthropathies, and trauma. These can broadly be categorized into amino acids plus related metabolites, fatty acids, ketones, and sugars. Conclusion. The role of metabolic profiling in orthopaedics is fast evolving with many metabolites already identified in a variety of pathologies. However, these results need to be interpreted with caution due to the presence of multiple confounding factors in many of the studies. Future research should include largescale epidemiological metabolic profiling studies incorporating various confounding factors with appropriate statistical analysis to account for multiple testing of the data. Cite this article:Bone Joint Res. 2020;9(3):108–119


Bone & Joint Research
Vol. 12, Issue 1 | Pages 33 - 45
16 Jan 2023
Li B Ding T Chen H Li C Chen B Xu X Huang P Hu F Guo L

Aims

Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis.

Methods

Minus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes. Chondrocytes were then stimulated to secrete exosomal miR-9-5p by cyclic tensile strain. Intra-articular injection of exosomal miR-9-5p into the model induced by destabilized medial meniscus (DMM) surgery was conducted to alleviate OA progression.


Bone & Joint Research
Vol. 8, Issue 5 | Pages 199 - 206
1 May 2019
Romanò CL Tsuchiya H Morelli I Battaglia AG Drago L

Implant-related infection is one of the leading reasons for failure in orthopaedics and trauma, and results in high social and economic costs. Various antibacterial coating technologies have proven to be safe and effective both in preclinical and clinical studies, with post-surgical implant-related infections reduced by 90% in some cases, depending on the type of coating and experimental setup used. Economic assessment may enable the cost-to-benefit profile of any given antibacterial coating to be defined, based on the expected infection rate with and without the coating, the cost of the infection management, and the cost of the coating. After reviewing the latest evidence on the available antibacterial coatings, we quantified the impact caused by delaying their large-scale application. Considering only joint arthroplasties, our calculations indicated that for an antibacterial coating, with a final user’s cost price of €600 and able to reduce post-surgical infection by 80%, each year of delay to its large-scale application would cause an estimated 35 200 new cases of post-surgical infection in Europe, equating to additional hospital costs of approximately €440 million per year. An adequate reimbursement policy for antibacterial coatings may benefit patients, healthcare systems, and related research, as could faster and more affordable regulatory pathways for the technologies still in the pipeline. This could significantly reduce the social and economic burden of implant-related infections in orthopaedics and trauma. Cite this article: C. L. Romanò, H. Tsuchiya, I. Morelli, A. G. Battaglia, L. Drago. Antibacterial coating of implants: are we missing something? Bone Joint Res 2019;8:199–206. DOI: 10.1302/2046-3758.85.BJR-2018-0316


Bone & Joint Research
Vol. 13, Issue 3 | Pages 110 - 123
7 Mar 2024
Xu J Ruan Z Guo Z Hou L Wang G Zheng Z Zhang X Liu H Sun K Guo F

Aims

Osteoarthritis (OA) is the most common chronic pathema of human joints. The pathogenesis is complex, involving physiological and mechanical factors. In previous studies, we found that ferroptosis is intimately related to OA, while the role of Sat1 in chondrocyte ferroptosis and OA, as well as the underlying mechanism, remains unclear.

Methods

In this study, interleukin-1β (IL-1β) was used to simulate inflammation and Erastin was used to simulate ferroptosis in vitro. We used small interfering RNA (siRNA) to knock down the spermidine/spermine N1-acetyltransferase 1 (Sat1) and arachidonate 15-lipoxygenase (Alox15), and examined damage-associated events including inflammation, ferroptosis, and oxidative stress of chondrocytes. In addition, a destabilization of the medial meniscus (DMM) mouse model of OA induced by surgery was established to investigate the role of Sat1 inhibition in OA progression.


Bone & Joint Research
Vol. 12, Issue 4 | Pages 259 - 273
6 Apr 2023
Lu R Wang Y Qu Y Wang S Peng C You H Zhu W Chen A

Aims

Osteoarthritis (OA) is a prevalent joint disorder with inflammatory response and cartilage deterioration as its main features. Dihydrocaffeic acid (DHCA), a bioactive component extracted from natural plant (gynura bicolor), has demonstrated anti-inflammatory properties in various diseases. We aimed to explore the chondroprotective effect of DHCA on OA and its potential mechanism.

Methods

In vitro, interleukin-1 beta (IL-1β) was used to establish the mice OA chondrocytes. Cell counting kit-8 evaluated chondrocyte viability. Western blotting analyzed the expression levels of collagen II, aggrecan, SOX9, inducible nitric oxide synthase (iNOS), IL-6, matrix metalloproteinases (MMPs: MMP1, MMP3, and MMP13), and signalling molecules associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Immunofluorescence analysis assessed the expression of aggrecan, collagen II, MMP13, and p-P65. In vivo, a destabilized medial meniscus (DMM) surgery was used to induce mice OA knee joints. After injection of DHCA or a vehicle into the injured joints, histological staining gauged the severity of cartilage damage.


Bone & Joint Research
Vol. 12, Issue 4 | Pages 274 - 284
11 Apr 2023
Du X Jiang Z Fang G Liu R Wen X Wu Y Hu S Zhang Z

Aims

This study aimed to investigate the role and mechanism of meniscal cell lysate (MCL) in fibroblast-like synoviocytes (FLSs) and osteoarthritis (OA).

Methods

Meniscus and synovial tissue were collected from 14 patients with and without OA. MCL and FLS proteins were extracted and analyzed by liquid chromatography‒mass spectrometry (LC‒MS). The roles of MCL and adenine nucleotide translocase 3 (ANT3) in FLSs were examined by enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunofluorescence, and transmission electron microscopy. Histological analysis was performed to determine ANT3 expression levels in a male mouse model.


Bone & Joint Research
Vol. 11, Issue 11 | Pages 835 - 842
17 Nov 2022
Wiesli MG Livio F Achermann Y Gautier E Wahl P

Aims

There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO4) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO4 applied locally to treat ODAI.

Methods

A total of 30 operations with ceftriaxone-loaded CaSO4 had been performed in 28 patients. Ceftriaxone was applied as a single local antibiotic in 21 operations and combined with vancomycin in eight operations, and in an additional operation with vancomycin and amphotericin B. Sampling of wound fluid was performed from drains or aspirations. Ceftriaxone concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS).


Bone & Joint Research
Vol. 13, Issue 6 | Pages 279 - 293
7 Jun 2024
Morris JL Letson HL McEwen PC Dobson GP

Aims

Adenosine, lidocaine, and Mg2+ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

Methods

Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 137 - 148
1 Apr 2024
Lu Y Ho T Huang C Yeh S Chen S Tsao Y

Aims

Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA).

Methods

Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers.


Bone & Joint Research
Vol. 7, Issue 12 | Pages 620 - 628
1 Dec 2018
Tätting L Sandberg O Bernhardsson M Ernerudh J Aspenberg† P

Objectives. Cortical and cancellous bone healing processes appear to be histologically different. They also respond differently to anti-inflammatory agents. We investigated whether the leucocyte composition on days 3 and 5 after cortical and cancellous injuries to bone was different, and compared changes over time using day 3 as the baseline. Methods. Ten-week-old male C56/Bl6J mice were randomized to either cancellous injury in the proximal tibia or cortical injury in the femoral diaphysis. Regenerating tissues were analyzed with flow cytometry at days 3 and 5, using panels with 15 antibodies for common macrophage and lymphocyte markers. The cellular response from day 3 to 5 was compared in order to identify differences in how cancellous and cortical bone healing develop. Results. Between day 3 and 5, the granulocytes increased in the cancellous model, whereas the lymphocytes (T cells, B cells, NK cells) and monocytes (CD11b+, F4/80+, CD206+, CD14+) increased in the cortical model. Conclusion. These results suggest an acute type of inflammation in cancellous bone healing, and a more chronic inflammation in cortical healing. This might explain, in part, why cancellous healing is faster and more resistant to anti-inflammatory drugs than are diaphyseal fractures. Cite this article: L. Tätting, O. Sandberg, M. Bernhardsson, J. Ernerudh, P. Aspenberg. Different composition of leucocytes in cortical and cancellous bone healing in a mouse model. Bone Joint Res 2018;7:620–628. DOI: 10.1302/2046-3758.712.BJR-2017-0366.R2


Bone & Joint Open
Vol. 3, Issue 11 | Pages 850 - 858
2 Nov 2022
Khoriati A Fozo ZA Al-Hilfi L Tennent D

Aims

The management of mid-shaft clavicle fractures (MSCFs) has evolved over the last three decades. Controversy exists over which specific fracture patterns to treat and when. This review aims to synthesize the literature in order to formulate an appropriate management algorithm for these injuries in both adolescents and adults.

Methods

This is a systematic review of clinical studies comparing the outcomes of operative and nonoperative treatments for MSCFs in the past 15 years. The literature was searched using, PubMed, Google scholar, OVID Medline, and Embase. All databases were searched with identical search terms: mid-shaft clavicle fractures (± fixation) (± nonoperative).


The Bone & Joint Journal
Vol. 105-B, Issue 7 | Pages 795 - 800
1 Jul 2023
Parsons N Achten J Costa ML

Aims

To report the outcomes of patients with a fracture of the distal tibia who were treated with intramedullary nail versus locking plate in the five years after participating in the Fixation of Distal Tibia fracture (FixDT) trial.

Methods

The FixDT trial reported the results for 321 patients randomized to nail or locking plate fixation in the first 12 months after their injury. In this follow-up study, we report the results of 170 of the original participants who agreed to be followed up until five years. Participants reported their Disability Rating Index (DRI) and health-related quality of life (EuroQol five-dimension three-level questionnaire) annually by self-reported questionnaire. Further surgical interventions related to the fracture were also recorded.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 588 - 595
17 Oct 2024
Breu R Avelar C Bertalan Z Grillari J Redl H Ljuhar R Quadlbauer S Hausner T

Aims

The aim of this study was to create artificial intelligence (AI) software with the purpose of providing a second opinion to physicians to support distal radius fracture (DRF) detection, and to compare the accuracy of fracture detection of physicians with and without software support.

Methods

The dataset consisted of 26,121 anonymized anterior-posterior (AP) and lateral standard view radiographs of the wrist, with and without DRF. The convolutional neural network (CNN) model was trained to detect the presence of a DRF by comparing the radiographs containing a fracture to the inconspicuous ones. A total of 11 physicians (six surgeons in training and five hand surgeons) assessed 200 pairs of randomly selected digital radiographs of the wrist (AP and lateral) for the presence of a DRF. The same images were first evaluated without, and then with, the support of the CNN model, and the diagnostic accuracy of the two methods was compared.


Bone & Joint Research
Vol. 12, Issue 3 | Pages 212 - 218
9 Mar 2023
Buchalter DB Kirby DJ Anil U Konda SR Leucht P

Aims

Glucose-insulin-potassium (GIK) is protective following cardiac myocyte ischaemia-reperfusion (IR) injury, however the role of GIK in protecting skeletal muscle from IR injury has not been evaluated. Given the similar mechanisms by which cardiac and skeletal muscle sustain an IR injury, we hypothesized that GIK would similarly protect skeletal muscle viability.

Methods

A total of 20 C57BL/6 male mice (10 control, 10 GIK) sustained a hindlimb IR injury using a 2.5-hour rubber band tourniquet. Immediately prior to tourniquet placement, a subcutaneous osmotic pump was placed which infused control mice with saline (0.9% sodium chloride) and treated mice with GIK (40% glucose, 50 U/l insulin, 80 mEq/L KCl, pH 4.5) at a rate of 16 µl/hr for 26.5 hours. At 24 hours following tourniquet removal, bilateral (tourniqueted and non-tourniqueted) gastrocnemius muscles were triphenyltetrazolium chloride (TTC)-stained to quantify percentage muscle viability. Bilateral peroneal muscles were used for gene expression analysis, serum creatinine and creatine kinase activity were measured, and a validated murine ethogram was used to quantify pain before euthanasia.


Bone & Joint Open
Vol. 5, Issue 10 | Pages 937 - 943
22 Oct 2024
Gregor RH Hooper GJ Frampton C

Aims

The aim of this study was to determine whether obesity had a detrimental effect on the long-term performance and survival of medial unicompartmental knee arthroplasties (UKAs).

Methods

This study reviewed prospectively collected functional outcome scores and revision rates of all medial UKA patients with recorded BMI performed in Christchurch, New Zealand, from January 2011 to September 2021. Patient-reported outcome measures (PROMs) were the primary outcome of this study, with all-cause revision rate analyzed as a secondary outcome. PROMs were taken preoperatively, at six months, one year, five years, and ten years postoperatively. There were 873 patients who had functional scores recorded at five years and 164 patients had scores recorded at ten years. Further sub-group analysis was performed based on the patient’s BMI. Revision data were available through the New Zealand Joint Registry for 2,323 UKAs performed during this time period.


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.


Bone & Joint Research
Vol. 12, Issue 3 | Pages 219 - 230
10 Mar 2023
Wang L Li S Xiao H Zhang T Liu Y Hu J Xu D Lu H

Aims

It has been established that mechanical stimulation benefits tendon-bone (T-B) healing, and macrophage phenotype can be regulated by mechanical cues; moreover, the interaction between macrophages and mesenchymal stem cells (MSCs) plays a fundamental role in tissue repair. This study aimed to investigate the role of macrophage-mediated MSC chondrogenesis in load-induced T-B healing in depth.

Methods

C57BL/6 mice rotator cuff (RC) repair model was established to explore the effects of mechanical stimulation on macrophage polarization, transforming growth factor (TGF)-β1 generation, and MSC chondrogenesis within T-B enthesis by immunofluorescence and enzyme-linked immunosorbent assay (ELISA). Macrophage depletion was performed by clodronate liposomes, and T-B healing quality was evaluated by histology and biomechanics. In vitro, bone marrow-derived macrophages (BMDMs) were stretched with CELLOAD-300 load system and macrophage polarization was identified by flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). MSC chondrogenic differentiation was measured by histochemical analysis and qRT-PCR. ELISA and qRT-PCR were performed to screen the candidate molecules that mediated the pro-chondrogenic function of mechanical stimulated BMDMs.


Bone & Joint Research
Vol. 13, Issue 3 | Pages 127 - 135
22 Mar 2024
Puetzler J Vallejo Diaz A Gosheger G Schulze M Arens D Zeiter S Siverino C Richards RG Moriarty TF

Aims

Fracture-related infection (FRI) is commonly classified based on the time of onset of symptoms. Early infections (< two weeks) are treated with debridement, antibiotics, and implant retention (DAIR). For late infections (> ten weeks), guidelines recommend implant removal due to tolerant biofilms. For delayed infections (two to ten weeks), recommendations are unclear. In this study we compared infection clearance and bone healing in early and delayed FRI treated with DAIR in a rabbit model.

Methods

Staphylococcus aureus was inoculated into a humeral osteotomy in 17 rabbits after plate osteosynthesis. Infection developed for one week (early group, n = 6) or four weeks (delayed group, n = 6) before DAIR (systemic antibiotics: two weeks, nafcillin + rifampin; four weeks, levofloxacin + rifampin). A control group (n = 5) received revision surgery after four weeks without antibiotics. Bacteriology of humerus, soft-tissue, and implants was performed seven weeks after revision surgery. Bone healing was assessed using a modified radiological union scale in tibial fractures (mRUST).


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.


Bone & Joint Open
Vol. 4, Issue 8 | Pages 602 - 611
21 Aug 2023
James HK Pattison GTR Griffin J Fisher JD Griffin DR

Aims

To evaluate if, for orthopaedic trainees, additional cadaveric simulation training or standard training alone yields superior radiological and clinical outcomes in patients undergoing dynamic hip screw (DHS) fixation or hemiarthroplasty for hip fracture.

Methods

This was a preliminary, pragmatic, multicentre, parallel group randomized controlled trial in nine secondary and tertiary NHS hospitals in England. Researchers were blinded to group allocation. Overall, 40 trainees in the West Midlands were eligible: 33 agreed to take part and were randomized, five withdrew after randomization, 13 were allocated cadaveric training, and 15 were allocated standard training. The intervention was an additional two-day cadaveric simulation course. The control group received standard on-the-job training. Primary outcome was implant position on the postoperative radiograph: tip-apex distance (mm) (DHS) and leg length discrepancy (mm) (hemiarthroplasty). Secondary clinical outcomes were procedure time, length of hospital stay, acute postoperative complication rate, and 12-month mortality. Procedure-specific secondary outcomes were intraoperative radiation dose (for DHS) and postoperative blood transfusion requirement (hemiarthroplasty).


Bone & Joint Research
Vol. 13, Issue 11 | Pages 647 - 658
12 Nov 2024
Li K Zhang Q

Aims

The incidence of limb fractures in patients living with HIV (PLWH) is increasing. However, due to their immunodeficiency status, the operation and rehabilitation of these patients present unique challenges. Currently, it is urgent to establish a standardized perioperative rehabilitation plan based on the concept of enhanced recovery after surgery (ERAS). This study aimed to validate the effectiveness of ERAS in the perioperative period of PLWH with limb fractures.

Methods

A total of 120 PLWH with limb fractures, between January 2015 and December 2023, were included in this study. We established a multidisciplinary team to design and implement a standardized ERAS protocol. The demographic, surgical, clinical, and follow-up information of the patients were collected and analyzed retrospectively.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 522 - 535
4 Sep 2023
Zhang G Li L Luo Z Zhang C Wang Y Kang X

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.


Bone & Joint Open
Vol. 3, Issue 11 | Pages 913 - 923
28 Nov 2022
Hareendranathan AR Wichuk S Punithakumar K Dulai S Jaremko J

Aims

Studies of infant hip development to date have been limited by considering only the changes in appearance of a single ultrasound slice (Graf’s standard plane). We used 3D ultrasound (3DUS) to establish maturation curves of normal infant hip development, quantifying variation by age, sex, side, and anteroposterior location in the hip.

Methods

We analyzed 3DUS scans of 519 infants (mean age 64 days (6 to 111 days)) presenting at a tertiary children’s hospital for suspicion of developmental dysplasia of the hip (DDH). Hips that did not require ultrasound follow-up or treatment were classified as ‘typically developing’. We calculated traditional DDH indices like α angle (αSP), femoral head coverage (FHCSP), and several novel indices from 3DUS like the acetabular contact angle (ACA) and osculating circle radius (OCR) using custom software.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 585 - 593
1 Aug 2022
Graham SM Jalal MMK Lalloo DG Hamish R. W. Simpson A

Aims

A number of anti-retroviral therapies (ART) have been implicated in potentially contributing to HIV-associated bone disease. The aim of this study was to evaluate the effect of combination ART on the fracture healing process.

Methods

A total of 16 adult male Wistar rats were randomly divided into two groups (n = eight each): Group 1 was given a combination of Tenfovir 30 mg, Lamivudine 30 mg, and Efavirenz 60 mg per day orally, whereas Group 2 was used as a control. After one week of medication preload, all rats underwent a standardized surgical procedure of mid-shaft tibial osteotomy fixed by intramedullary nail with no gap at the fracture site. Progress in fracture healing was monitored regularly for eight weeks. Further evaluations were carried out after euthanasia by micro-CT, mechanically and histologically. Two blinded orthopaedic surgeons used the Radiological Union Scoring system for the Tibia (RUST) to determine fracture healing.


Bone & Joint Open
Vol. 5, Issue 3 | Pages 236 - 242
22 Mar 2024
Guryel E McEwan J Qureshi AA Robertson A Ahluwalia R

Aims

Ankle fractures are common injuries and the third most common fragility fracture. In all, 40% of ankle fractures in the frail are open and represent a complex clinical scenario, with morbidity and mortality rates similar to hip fracture patients. They have a higher risk of complications, such as wound infections, malunion, hospital-acquired infections, pressure sores, veno-thromboembolic events, and significant sarcopaenia from prolonged bed rest.

Methods

A modified Delphi method was used and a group of experts with a vested interest in best practice were invited from the British Foot and Ankle Society (BOFAS), British Orthopaedic Association (BOA), Orthopaedic Trauma Society (OTS), British Association of Plastic & Reconstructive Surgeons (BAPRAS), British Geriatric Society (BGS), and the British Limb Reconstruction Society (BLRS).


Bone & Joint Open
Vol. 5, Issue 9 | Pages 793 - 799
20 Sep 2024
Cederqvist S Flinkkilä T Tuominen A Sormaala M Ylinen J Kautiainen H Sirniö K Pamilo K Kiviranta I Paloneva J

Aims

Rotator cuff disease (RCD) can considerably decrease quality of life. Here, we investigated whether health-related quality of life (HRQoL) influences the need for surgery in patients with RCD.

Methods

We performed an analysis of 417 patients with symptomatic RCD who were recruited from two hospitals between June 2008 and December 2014 to be randomized to receive non-surgical or surgical treatment. After a three-month rehabilitation period, 36-Item Short-Form Health Survey questionnaire (SF-36), shoulder pain (visual analogue scale (VAS)), and shoulder function (Constant-Murley score) data were available from 191 still-symptomatic patients who were eligible for surgery. A control group was formed from 87 excluded patients who were no longer eligible for surgery due to relief of symptoms.


Bone & Joint Open
Vol. 4, Issue 8 | Pages 612 - 620
21 Aug 2023
Martin J Johnson NA Shepherd J Dias J

Aims

There is ambiguity surrounding the degree of scaphoid union required to safely allow mobilization following scaphoid waist fracture. Premature mobilization could lead to refracture, but late mobilization may cause stiffness and delay return to normal function. This study aims to explore the risk of refracture at different stages of scaphoid waist fracture union in three common fracture patterns, using a novel finite element method.

Methods

The most common anatomical variant of the scaphoid was modelled from a CT scan of a healthy hand and wrist using 3D Slicer freeware. This model was uploaded into COMSOL Multiphysics software to enable the application of physiological enhancements. Three common waist fracture patterns were produced following the Russe classification. Each fracture had differing stages of healing, ranging from 10% to 90% partial union, with increments of 10% union assessed. A physiological force of 100 N acting on the distal pole was applied, with the risk of refracture assessed using the Von Mises stress.


Bone & Joint Open
Vol. 5, Issue 2 | Pages 94 - 100
5 Feb 2024
Mancino F Kayani B Gabr A Fontalis A Plastow R Haddad FS

Anterior cruciate ligament (ACL) injuries are among the most common and debilitating knee injuries in professional athletes with an incidence in females up to eight-times higher than their male counterparts. ACL injuries can be career-threatening and are associated with increased risk of developing knee osteoarthritis in future life. The increased risk of ACL injury in females has been attributed to various anatomical, developmental, neuromuscular, and hormonal factors. Anatomical and hormonal factors have been identified and investigated as significant contributors including osseous anatomy, ligament laxity, and hamstring muscular recruitment. Postural stability and impact absorption are associated with the stabilizing effort and stress on the ACL during sport activity, increasing the risk of noncontact pivot injury. Female patients have smaller diameter hamstring autografts than males, which may predispose to increased risk of re-rupture following ACL reconstruction and to an increased risk of chondral and meniscal injuries. The addition of an extra-articular tenodesis can reduce the risk of failure; therefore, it should routinely be considered in young elite athletes. Prevention programs target key aspects of training including plyometrics, strengthening, balance, endurance and stability, and neuromuscular training, reducing the risk of ACL injuries in female athletes by up to 90%. Sex disparities in access to training facilities may also play an important role in the risk of ACL injuries between males and females. Similarly, football boots, pitches quality, and football size and weight should be considered and tailored around females’ characteristics. Finally, high levels of personal and sport-related stress have been shown to increase the risk of ACL injury which may be related to alterations in attention and coordination, together with increased muscular tension, and compromise the return to sport after ACL injury. Further investigations are still necessary to better understand and address the risk factors involved in ACL injuries in female athletes.

Cite this article: Bone Jt Open 2024;5(2):94–100.


Bone & Joint Open
Vol. 5, Issue 2 | Pages 117 - 122
9 Feb 2024
Chaturvedi A Russell H Farrugia M Roger M Putti A Jenkins PJ Feltbower S

Aims

Occult (clinical) injuries represent 15% of all scaphoid fractures, posing significant challenges to the clinician. MRI has been suggested as the gold standard for diagnosis, but remains expensive, time-consuming, and is in high demand. Conventional management with immobilization and serial radiography typically results in multiple follow-up attendances to clinic, radiation exposure, and delays return to work. Suboptimal management can result in significant disability and, frequently, litigation.

Methods

We present a service evaluation report following the introduction of a quality-improvement themed, streamlined, clinical scaphoid pathway. Patients are offered a removable wrist splint with verbal and written instructions to remove it two weeks following injury, for self-assessment. The persistence of pain is the patient’s guide to ‘opt-in’ and to self-refer for a follow-up appointment with a senior emergency physician. On confirmation of ongoing signs of clinical scaphoid injury, an urgent outpatient ‘fast’-wrist protocol MRI scan is ordered, with instructions to maintain wrist immobilization. Patients with positive scan results are referred for specialist orthopaedic assessment via a virtual fracture clinic.


Bone & Joint Open
Vol. 4, Issue 9 | Pages 713 - 719
19 Sep 2023
Gregersen MG Justad-Berg RT Gill NEQ Saatvedt O Aas LK Molund M

Aims

Treatment of Weber B ankle fractures that are stable on weightbearing radiographs but unstable on concomitant stress tests (classified SER4a) is controversial. Recent studies indicate that these fractures should be treated nonoperatively, but no studies have compared alternative nonoperative options. This study aims to evaluate patient-reported outcomes and the safety of fracture treatment using functional orthosis versus cast immobilization.

Methods

A total of 110 patients with Weber B/SER4a ankle fractures will be randomized (1:1 ratio) to receive six weeks of functional orthosis treatment or cast immobilization with a two-year follow-up. The primary outcome is patient-reported ankle function and symptoms measured by the Manchester-Oxford Foot and Ankle Questionnaire (MOxFQ); secondary outcomes include Olerud-Molander Ankle Score, radiological evaluation of ankle congruence in weightbearing and gravity stress tests, and rates of treatment-related adverse events. The Regional Committee for Medical and Health Research (approval number 277693) has granted ethical approval, and the study is funded by South-Eastern Norway Regional Health Authority (grant number 2023014).


Bone & Joint Open
Vol. 5, Issue 11 | Pages 977 - 983
5 Nov 2024
Danielsen O Jensen CB Varnum C Jakobsen T Andersen MR Bieder MJ Overgaard S Jørgensen CC Kehlet H Gromov K Lindberg-Larsen M

Aims

Day-case success rates after primary total hip arthroplasty (THA), total knee arthroplasty (TKA), and medial unicompartmental knee arthroplasty (mUKA) may vary, and detailed data are needed on causes of not being discharged. The aim of this study was to analyze the association between surgical procedure type and successful day-case surgery, and to analyze causes of not being discharged on the day of surgery when eligible and scheduled for day-case THA, TKA, and mUKA.

Methods

A multicentre, prospective consecutive cohort study was carried out from September 2022 to August 2023. Patients were screened for day-case eligibility using well defined inclusion and exclusion criteria, and discharged when fulfilling predetermined discharge criteria. Day-case eligible patients were scheduled for surgery with intended start of surgery before 1.00 pm.