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Bone & Joint Research
Vol. 13, Issue 7 | Pages 321 - 331
3 Jul 2024
Naito T Yamanaka Y Tokuda K Sato N Tajima T Tsukamoto M Suzuki H Kawasaki M Nakamura E Sakai A

Aims

The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

Methods

Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 149 - 156
4 Apr 2024
Rajamäki A Lehtovirta L Niemeläinen M Reito A Parkkinen J Peräniemi S Vepsäläinen J Eskelinen A

Aims. Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium. Methods. Periprosthetic metal concentrations in the synovia and histopathological samples were analyzed from 230 patients from our institution from October 2016 to December 2019. An ordinal regression model was calculated to investigate the effect of the accumulated metals on the histopathological reaction of the synovia. Results. Median metal concentrations were as follows: cobalt: 0.69 μg/g (interquartile range (IQR) 0.10 to 6.10); chromium: 1.1 μg/g (IQR 0.27 to 4.10); and titanium: 1.6 μg/g (IQR 0.90 to 4.07). Moderate ALVAL scores were found in 30% (n = 39) of the revised knees. There were ten patients with an ALVAL score of 6 or more who were revised for suspected periprosthetic joint infection (PJI), aseptic loosening, or osteolysis. R2 varied between 0.269 and 0.369 for the ordinal regression models. The most important variables were model type, indication for revision, and cobalt and chromium in the ordinal regression models. Conclusion. We found that metal particles released from the knee prosthesis can accumulate in the periprosthetic tissues. Several patients revised for suspected culture-negative PJI had features of an ALVAL reaction, which is a novel finding. Therefore, ALVAL-type reactions can also be found around knee prostheses, but they are mostly mild and less common than those found around metal-on-metal prostheses. Cite this article: Bone Joint Res 2024;13(4):149–156


Bone & Joint Research
Vol. 13, Issue 2 | Pages 66 - 82
5 Feb 2024
Zhao D Zeng L Liang G Luo M Pan J Dou Y Lin F Huang H Yang W Liu J

Aims

This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA.

Methods

Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization.


Bone & Joint Open
Vol. 4, Issue 3 | Pages 158 - 167
10 Mar 2023
Landers S Hely R Hely A Harrison B Page RS Maister N Gwini SM Gill SD

Aims

This study investigated the effects of transcatheter arterial embolization (TAE) on pain, function, and quality of life in people with early-stage symptomatic knee osteoarthritis (OA) compared to a sham procedure.

Methods

A total of 59 participants with symptomatic Kellgren-Lawrence grade 2 knee OA were randomly allocated to TAE or a sham procedure. The intervention group underwent TAE of one or more genicular arteries. The control group received a blinded sham procedure. The primary outcome was knee pain at 12 months according to the Knee injury and Osteoarthritis Outcome Score (KOOS) pain scale. Secondary outcomes included self-reported function and quality of life (KOOS, EuroQol five-dimension five-level questionnaire (EQ-5D-5L)), self-reported Global Change, six-minute walk test, 30-second chair stand test, and adverse events. Subgroup analyses compared participants who received complete embolization of all genicular arteries (as distinct from embolization of some arteries) (n = 17) with the control group (n = 29) for KOOS and Global Change scores at 12 months. Continuous variables were analyzed with quantile regression, adjusting for baseline scores. Dichotomized variables were analyzed with chi-squared tests.


Bone & Joint Research
Vol. 10, Issue 4 | Pages 269 - 276
1 Apr 2021
Matsubara N Nakasa T Ishikawa M Tamura T Adachi N

Aims

Meniscal injuries are common and often induce knee pain requiring surgical intervention. To develop effective strategies for meniscus regeneration, we hypothesized that a minced meniscus embedded in an atelocollagen gel, a firm gel-like material, may enhance meniscus regeneration through cell migration and proliferation in the gel. Hence, the objective of this study was to investigate cell migration and proliferation in atelocollagen gels seeded with autologous meniscus fragments in vitro and examine the therapeutic potential of this combination in an in vivo rabbit model of massive meniscus defect.

Methods

A total of 34 Japanese white rabbits (divided into defect and atelocollagen groups) were used to produce the massive meniscus defect model through a medial patellar approach. Cell migration and proliferation were evaluated using immunohistochemistry. Furthermore, histological evaluation of the sections was performed, and a modified Pauli’s scoring system was used for the quantitative evaluation of the regenerated meniscus.


Aims

Proliferation, migration, and differentiation of anterior cruciate ligament (ACL) remnant and surrounding cells are fundamental processes for ACL reconstruction; however, the interaction between ACL remnant and surrounding cells is unclear. We hypothesized that ACL remnant cells preserve the capability to regulate the surrounding cells’ activity, collagen gene expression, and tenogenic differentiation. Moreover, extracorporeal shock wave (ESW) would not only promote activity of ACL remnant cells, but also enhance their paracrine regulation of surrounding cells.

Methods

Cell viability, proliferation, migration, and expression levels of Collagen-I (COL-I) A1, transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF) were compared between ACL remnant cells untreated and treated with ESW (0.15 mJ/mm2, 1,000 impulses, 4 Hz). To evaluate the subsequent effects on the surrounding cells, bone marrow stromal cells (BMSCs)’ viability, proliferation, migration, and levels of Type I Collagen, Type III Collagen, and tenogenic gene (Scx, TNC) expression were investigated using coculture system.


The Bone & Joint Journal
Vol. 101-B, Issue 10 | Pages 1238 - 1247
1 Oct 2019
Soreide E Denbeigh JM Lewallen EA Thaler R Xu W Berglund L Yao JJ Martinez A Nordsletten L van Wijnen AJ Kakar S

Aims

Options for the treatment of intra-articular ligament injuries are limited, and insufficient ligament reconstruction can cause painful joint instability, loss of function, and progressive development of degenerative arthritis. This study aimed to assess the capability of a biologically enhanced matrix material for ligament reconstruction to withstand tensile forces within the joint and enhance ligament regeneration needed to regain joint function.

Materials and Methods

A total of 18 New Zealand rabbits underwent bilateral anterior cruciate ligament reconstruction by autograft, FiberTape, or FiberTape-augmented autograft. Primary outcomes were biomechanical assessment (n = 17), microCT (µCT) assessment (n = 12), histological evaluation (n = 12), and quantitative polymerase chain reaction (qPCR) analysis (n = 6).


The Bone & Joint Journal
Vol. 101-B, Issue 7 | Pages 824 - 831
1 Jul 2019
Mahmoud EE Adachi N Mawas AS Deie M Ochi M

Aim

Mesenchymal stem cells (MSCs) have several properties that may support their use as an early treatment option for osteoarthritis (OA). This study investigated the role of multiple injections of allogeneic bone marrow-derived stem cells (BMSCs) to alleviate the progression of osteoarthritic changes in the various structures of the mature rabbit knee in an anterior cruciate ligament (ACL)-deficient OA model.

Materials and Methods

Two months after bilateral section of the ACL of Japanese white rabbits aged nine months or more, either phosphate buffered saline (PBS) or 1 x 106 MSCs were injected into the knee joint in single or three consecutive doses. After two months, the articular cartilage and meniscus were assessed macroscopically, histologically, and immunohistochemically using collagen I and II.


The Bone & Joint Journal
Vol. 100-B, Issue 11 | Pages 1471 - 1476
1 Nov 2018
Weston JT Watts CD Mabry TM Hanssen AD Berry DJ Abdel MP

Aims

The results of irrigation and debridement with component retention (IDCR) in the treatment of acutely infected total knee arthroplasties (TKAs) have been variable. The aim of this study was to assess the outcome after IDCR when combined with chronic antibiotic suppression. We also evaluated survivorship free from subsequent infection, removal of the components, and death, as well as the risk factors for failure.

Patients and Methods

This was a single-centre retrospective review of 134 infected primary TKAs that were treated with IDCR. Infections within four weeks of the procedure were defined as acute postoperative infections, and those occurring more than four weeks after the procedure with symptoms for less than three weeks were defined as acute haematogenous infections. Patients were treated with intravenous antibiotics for four to six weeks, followed by chronic oral antibiotic suppression. Estimates of survival were made using a competing risk analysis. The mean follow-up was five years (2.1 to 13).


The Bone & Joint Journal
Vol. 99-B, Issue 11 | Pages 1477 - 1481
1 Nov 2017
Hernandez NM Taunton MJ Perry KI Mara KC Hanssen AD Abdel MP

Aims

Patients with flexion instability after total knee arthroplasty (TKA) often present with a recurrent effusion, which may be a haemarthrosis. While the radiographic factors contributing to flexion instability have been elucidated, the clinical diagnosis remains challenging. Our aim, in this study, was to determine the mean white cell count and differential profile in pre-operative aspirations of synovial fluid in a consecutive series of patients undergoing revision TKA for flexion instability.

Patients and Methods

Between 2000 and 2010, 60 patients undergoing aseptic revision TKA for flexion instability were identified. The results of the pre-operative aspiration of synovial fluid were available for 53 patients (88%). These patients were 1:2 matched to 106 patients who underwent aseptic TKA for indications other than flexion instability. The mean age of the patients at revision TKA was 65 years (44 to 82) and 55% were women. The mean follow-up was 4.3 years (2 to 10.2).


The Bone & Joint Journal
Vol. 99-B, Issue 6 | Pages 788 - 792
1 Jun 2017
Bradley B Middleton S Davis N Williams M Stocker M Hockings M Isaac DL

Aims

Unicompartmental knee arthroplasty (UKA) has been successfully performed in the United States healthcare system on outpatients. Despite differences in healthcare structure and financial environment, we hypothesised that it would be feasible to replicate this success and perform UKA with safe day of surgery discharge within the NHS, in the United Kingdom. This has not been reported in any other United Kingdom centres.

Patients and Methods

We report our experience of implementing a pathway to allow safe day of surgery discharge following UKA. Data were prospectively collected on 72 patients who underwent UKA as a day case between December 2011 and September 2015.


The Bone & Joint Journal
Vol. 99-B, Issue 3 | Pages 344 - 350
1 Mar 2017
Metcalfe AJ Clark DA Kemp MA Eldridge JD

Aims

The Bereiter trochleoplasty has been used in our unit for 12 years to manage recurrent patellar instability in patients with severe trochlea dysplasia. The aim of this study was to document the outcome of a large consecutive cohort of patients who have undergone this operation.

Patients and Methods

Between June 2002 and August 2013, 214 consecutive trochleoplasties were carried out in 185 patients. There were 133 women and 52 men with a mean age of 21.3 years (14 to 38). All patients were offered yearly clinical and radiological follow-up. They completed the following patient reported outcome scores (PROMs): International Knee Documentation Committee subjective scale, the Kujala score, the Western Ontario and McMaster Universities Arthritis Index score and the short-form (SF)-12.


The Bone & Joint Journal
Vol. 98-B, Issue 10_Supple_B | Pages 34 - 40
1 Oct 2016
Emerson RH Alnachoukati O Barrington J Ennin K

Aims

Approved by the Food and Drug Administration in 2004, the Phase III Oxford Medial Partial Knee is used to treat anteromedial osteoarthritis (AMOA) in patients with an intact anterior cruciate ligament. This unicompartmental knee arthroplasty (UKA) is relatively new in the United States, and therefore long-term American results are lacking.

Patients and Methods

This is a single surgeon, retrospective study based on prospectively collected data, analysing a consecutive series of primary UKAs using the Phase III mobile-bearing Oxford Knee and Phase III instrumentation.

Between July 2004 and December 2006, the senior author (RHE) carried out a medial UKA in 173 patients (213 knees) for anteromedial osteoarthritis or avascular necrosis (AVN).

A total of 95 patients were men and 78 were women. Their mean age at surgery was 67 years (38 to 89) and mean body mass index 29.87 kg/m2 (17 to 62).

The mean follow-up was ten years (4 to 11).


Bone & Joint Research
Vol. 5, Issue 9 | Pages 436 - 441
1 Sep 2016
Pinsornsak P Naratrikun K Kanitnate S Sangkomkamhang T

Objectives

The purpose of this study was to compare the joint space width between one-leg and both-legs standing radiographs in order to diagnose a primary osteoarthritis of the knee.

Methods

Digital radiographs of 100 medial osteoarthritic knees in 50 patients were performed. The patients had undergone one-leg standing anteroposterior (AP) views by standing on the affected leg while a both-legs standing AP view was undertaken while standing on both legs. The severity of the osteoarthritis was evaluated using the joint space width and Kellgren-Lawrence (KL) radiographic classification. The t-test was used for statistical analysis.


The Bone & Joint Journal
Vol. 97-B, Issue 9 | Pages 1220 - 1225
1 Sep 2015
Chen LB Wang H Tie K Mohammed A Qi YJ

A total of 22 patients with a tibial avulsion fracture involving the insertion of the posterior cruciate ligament (PCL) with grade II or III posterior laxity were reduced and fixed arthroscopically using routine anterior and double posteromedial portals. A double-strand Ethibond suture was inserted into the joint and wrapped around the PCL from anterior to posterior to secure the ligament above the avulsed bony fragment. Two tibial bone tunnels were created using the PCL reconstruction guide, aiming at the medial and lateral borders of the tibial bed. The ends of the suture were pulled out through the bone tunnels and tied over the tibial cortex between the openings of the tunnels to reduce and secure the bony fragment. Satisfactory reduction of the fracture was checked arthroscopically and radiographically.

The patients were followed-up for a mean of 24.5 months (19 to 28). Bone union occurred six weeks post-operatively. At final follow-up, all patients had a negative posterior drawer test and a full range of movement. KT-1000 arthrometer examination showed that the mean post-operative side-to-side difference improved from 10.9 mm (standard deviation (sd) 0.7) pre-operatively to 1.5 mm (sd 0.6) (p = 0.001). The mean Tegner and the International Knee Documentation Committee scores improved significantly (p = 0.001). The mean Lysholm score at final follow-up was 92.0 (85 to 96).

We conclude that this technique is convenient, reliable and minimally invasive and successfully restores the stability and function of the knee.

Cite this article: Bone Joint J 2015;97-B:1220–5.


The Bone & Joint Journal
Vol. 96-B, Issue 10 | Pages 1319 - 1324
1 Oct 2014
Oh JS Youm YS Cho SD Choi SW Cho YJ

Previous studies support the important role of vascular endothelial growth factor (VEGF) and syndecan-4 in the pathogenesis of osteoarthritis (OA). Both VEGF and syndecan-4 are expressed by chondrocytes and both are involved in the regulation of matrix metalloproteinase-3, resulting in the activation of aggrecanase II (ADAMTS-5), which is essential in the pathogenesis of OA. However, the relationship between VEGF and syndecan-4 has not been established. As a pilot study, we assayed the expression of VEGF and syndecan-4 in cartilage samples and cultured chondrocytes from osteoarthritic knee joints and analysed the relationship between these two factors.

Specimens were collected from 21 female patients (29 knees) who underwent total knee replacement due to severe medial OA of the knee (Kellgren–Lawrence grade 4). Articular cartilage samples, obtained from bone and cartilage excised during surgery, were analysed and used for chondrocyte culture. We found that the levels of expression of VEGF and syndecan-4 mRNA did not differ significantly between medial femoral cartilage with severe degenerative changes and lateral femoral cartilage that appeared grossly normal (p = 0.443 and 0.622, respectively). Likewise, the levels of expression of VEGF and syndecan-4 mRNA were similar in cultured chondrocytes from medial and lateral femoral cartilage. The levels of expression of VEGF and syndecan-4 mRNAs were significantly and positively correlated in cartilage explant (r = 0.601, p = 0.003) but not in cultured chondrocytes. These results suggest that there is a close relationship between VEGF and syndecan-4 in the cartilage of patients with OA. Further studies are needed to determine the exact pathway by which these two factors interact in the pathogenesis of OA.

Cite this article: Bone Joint J 2014;96-B:1319–24.


The Bone & Joint Journal
Vol. 96-B, Issue 6 | Pages 759 - 764
1 Jun 2014
Tibrewal S Malagelada F Jeyaseelan L Posch F Scott G

Peri-prosthetic infection is amongst the most common causes of failure following total knee replacement (TKR). In the presence of established infection, thorough joint debridement and removal of all components is necessary following which new components may be implanted. This can be performed in one or two stages; two-stage revision with placement of an interim antibiotic-loaded spacer is regarded by many to be the standard procedure for eradication of peri-prosthetic joint infection.

We present our experience of a consecutive series of 50 single-stage revision TKRs for established deep infection performed between 1979 and 2010. There were 33 women and 17 men with a mean age at revision of 66.8 years (42 to 84) and a mean follow-up of 10.5 years (2 to 24). The mean time between the primary TKR and the revision procedure was 2.05 years (1 to 8).

Only one patient required a further revision for recurrent infection, representing a success rate of 98%. Nine patients required further revision for aseptic loosening, according to microbiological testing of biopsies taken at the subsequent surgery. Three other patients developed a further septic episode but none required another revision.

These results suggest that a single-stage revision can produce comparable results to a two-stage revision. Single-stage revision offers a reduction in costs as well as less morbidity and inconvenience for patients.

Cite this article: Bone Joint J 2014;96-B:759–64.


Bone & Joint Research
Vol. 3, Issue 6 | Pages 203 - 211
1 Jun 2014
Onur T Wu R Metz L Dang A

Objectives

Our objective in this article is to test the hypothesis that type 2 diabetes mellitus (T2DM) is a factor in the onset and progression of osteoarthritis, and to characterise the quality of the articular cartilage in an appropriate rat model.

Methods

T2DM rats were obtained from the UC Davis group and compared with control Lewis rats. The diabetic rats were sacrificed at ages from six to 12 months, while control rats were sacrificed at six months only. Osteoarthritis severity was determined via histology in four knee quadrants using the OARSI scoring guide. Immunohistochemical staining was also performed as a secondary form of osteoarthritic analysis.


Bone & Joint Research
Vol. 3, Issue 4 | Pages 89 - 94
1 Apr 2014
Cook JL Hung CT Kuroki K Stoker AM Cook CR Pfeiffer FM Sherman SL Stannard JP

Cartilage repair in terms of replacement, or regeneration of damaged or diseased articular cartilage with functional tissue, is the ‘holy grail’ of joint surgery. A wide spectrum of strategies for cartilage repair currently exists and several of these techniques have been reported to be associated with successful clinical outcomes for appropriately selected indications. However, based on respective advantages, disadvantages, and limitations, no single strategy, or even combination of strategies, provides surgeons with viable options for attaining successful long-term outcomes in the majority of patients. As such, development of novel techniques and optimisation of current techniques need to be, and are, the focus of a great deal of research from the basic science level to clinical trials. Translational research that bridges scientific discoveries to clinical application involves the use of animal models in order to assess safety and efficacy for regulatory approval for human use. This review article provides an overview of animal models for cartilage repair.

Cite this article: Bone Joint Res 2014;4:89–94.


The Bone & Joint Journal
Vol. 95-B, Issue 4 | Pages 478 - 485
1 Apr 2013
Naveed MA Ackroyd CE Porteous AJ

We present the ten- to 15-year follow-up of 31 patients (34 knees), who underwent an Elmslie-Trillat tibial tubercle osteotomy for chronic, severe patellar instability, unresponsive to non-operative treatment. The mean age of the patients at the time of surgery was 31 years (18 to 46) and they were reviewed post-operatively, at four years (2 to 8) and then at 12 years (10 to 15). All patients had pre-operative knee radiographs and Cox and Insall knee scores. Superolateral portal arthroscopy was performed per-operatively to document chondral damage and after the osteotomy to assess the stability of the patellofemoral joint. A total of 28 knees (82%) had a varying degree of damage to the articular surface. At final follow-up 25 patients (28 knees) were available for review and underwent clinical examination, radiographs of the knee, and Cox and Insall scoring. Six patients who had no arthroscopic chondral abnormality showed no or only early signs of osteoarthritis on final radiographs; while 12 patients with lower grade chondral damage (grade 1 to 2) showed early to moderate signs of osteoarthritis and six out of ten knees with higher grade chondral damage (grade 3 to 4) showed marked evidence of osteoarthritis; four of these had undergone a knee replacement. In the 22 patients (24 knees) with complete follow-up, 19 knees (79.2%) were reported to have a good or excellent outcome at four years, while 15 knees (62.5%) were reported to have the same at long-term follow-up. The functional and radiological results show that the extent of pre-operatively sustained chondral damage is directly related to the subsequent development of patellofemoral osteoarthritis.

Cite this article: Bone Joint J 2013;95-B:478–85.