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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 Mg. 2+. (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. Results. Despite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased. Conclusion. At 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials. Cite this article: Bone Joint Res 2024;13(6):279–293


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.


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 11 | Pages 881 - 888
21 Nov 2023
Denyer S Eikani C Sheth M Schmitt D Brown N

Aims

The diagnosis of periprosthetic joint infection (PJI) can be challenging as the symptoms are similar to other conditions, and the markers used for diagnosis have limited sensitivity and specificity. Recent research has suggested using blood cell ratios, such as platelet-to-volume ratio (PVR) and platelet-to-lymphocyte ratio (PLR), to improve diagnostic accuracy. The aim of the study was to further validate the effectiveness of PVR and PLR in diagnosing PJI.

Methods

A retrospective review was conducted to assess the accuracy of different marker combinations for diagnosing chronic PJI. A total of 573 patients were included in the study, of which 124 knees and 122 hips had a diagnosis of chronic PJI. Complete blood count and synovial fluid analysis were collected. Recently published blood cell ratio cut-off points were applied to receiver operating characteristic curves for all markers and combinations. The area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values were calculated.


The Bone & Joint Journal
Vol. 103-B, Issue 1 | Pages 113 - 122
1 Jan 2021
Kayani B Tahmassebi J Ayuob A Konan S Oussedik S Haddad FS

Aims

The primary aim of this study was to compare the postoperative systemic inflammatory response in conventional jig-based total knee arthroplasty (conventional TKA) versus robotic-arm assisted total knee arthroplasty (robotic TKA). Secondary aims were to compare the macroscopic soft tissue injury, femoral and tibial bone trauma, localized thermal response, and the accuracy of component positioning between the two treatment groups.

Methods

This prospective randomized controlled trial included 30 patients with osteoarthritis of the knee undergoing conventional TKA versus robotic TKA. Predefined serum markers of inflammation and localized knee temperature were collected preoperatively and postoperatively at six hours, day 1, day 2, day 7, and day 28 following TKA. Blinded observers used the Macroscopic Soft Tissue Injury (MASTI) classification system to grade intraoperative periarticular soft tissue injury and bone trauma. Plain radiographs were used to assess the accuracy of achieving the planned postioning of the components in both groups.


The Bone & Joint Journal
Vol. 102-B, Issue 11 | Pages 1527 - 1534
3 Nov 2020
Orita K Minoda Y Sugama R Ohta Y Ueyama H Takemura S Nakamura H

Aims

Vitamin E-infused highly cross-linked polyethylene (E1) has recently been introduced in total knee arthroplasty (TKA). An in vitro wear simulator study showed that E1 reduced polyethylene wear. However there is no published information regarding in vivo wear. Previous reports suggest that newly introduced materials which reduce in vitro polyethylene wear do not necessarily reduce in vivo polyethylene wear. To assist in the evaluation of the newly introduced material before widespread use, we established an in vivo polyethylene wear particle analysis for TKA. The aim of this study was to compare in vivo polyethylene wear particle generation between E1 and conventional polyethylene (ArCom) in TKA.

Methods

A total of 34 knees undergoing TKA (17 each with ArCom or E1) were investigated. Except for the polyethylene insert material, the prostheses used for both groups were identical. Synovial fluid was obtained at a mean of 3.4 years (SD 1.3) postoperatively. The in vivo polyethylene wear particles were isolated from the synovial fluid using a previously validated method and examined by scanning electron microscopy.


Bone & Joint Research
Vol. 9, Issue 9 | Pages 543 - 553
1 Sep 2020
Bakirci E Tschan K May RD Ahmad SS Kleer B Gantenbein B

Aims

The anterior cruciate ligament (ACL) is known to have a poor wound healing capacity, whereas other ligaments outside of the knee joint capsule such as the medial collateral ligament (MCL) apparently heal more easily. Plasmin has been identified as a major component in the synovial fluid that varies among patients. The aim of this study was to test whether plasmin, a component of synovial fluid, could be a main factor responsible for the poor wound healing capacity of the ACL.

Methods

The effects of increasing concentrations of plasmin (0, 0.1, 1, 10, and 50 µg/ml) onto the wound closing speed (WCS) of primary ACL-derived ligamentocytes (ACL-LCs) were tested using wound scratch assay and time-lapse phase-contrast microscopy. Additionally, relative expression changes (quantitative PCR (qPCR)) of major LC-relevant genes and catabolic genes were investigated. The positive controls were 10% fetal calf serum (FCS) and platelet-derived growth factor (PDGF).


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). Results. In the flexion instability group, the median total cell count was 312 cells/µL (interquartile range (IQR) 104 to 624), with a mean distribution of 45% macrophages (2% to 90%), 30% lymphocytes (1% to 69%), 18% neutrophils (0% to 80%), 0.5% eosinophils (0% to 6%) and 7% other cells (0% to 42%; mainly synovial cells). There was no significant difference in the median total cell count (p = 0.14) or mean distribution of macrophages (p = 0.42), lymphocytes (p = 0.38), neutrophils (p = 0.19) and eosinophils (p = 0.89) between the flexion instability and control groups. There was a significant difference in the percentage of bloody serosanguineous aspirations which was 58% in the flexion instability group and 18% in the control group (odds ratio = 6.5; p = 0.0001). Conclusions. In the group of patients who underwent revision TKA for flexion instability, most had a mean cell count and differential similar to those who underwent revision for other aseptic indications. However, bloody serosanguineous aspirations were 6.5 times more common in those with flexion instability confirming that many of the recurrent effusions seen in this condition are haemarthroses. Cite this article: Bone Joint J 2017;99-B:1477–81


The Bone & Joint Journal
Vol. 98-B, Issue 4 | Pages 437 - 441
1 Apr 2016
Middleton S Toms A

We explored the literature surrounding whether allergy and hypersensitivity has a clinical basis for implant selection in total knee arthroplasty (TKA). In error, the terms hypersensitivity and allergy are often used synonymously. Although a relationship is present, we could not find any evidence of implant failure due to allergy. There is however increasing basic science that suggests a link between loosening and metal ion production. This is not an allergic response but is a potential problem. With a lack of evidence logically there can be no justification to use ‘hypoallergenic’ implants in patients who have pre-existing skin sensitivity to the metals used in TKA.

Cite this article: Bone Joint J 2016;98-B:437–41.


Bone & Joint Research
Vol. 3, Issue 4 | Pages 108 - 116
1 Apr 2014
Cheng K Giebaly D Campbell A Rumley A Lowe G

Objective

Mortality rates reported by the National Joint Registry for England and Wales (NJR) were higher following cemented total knee replacement (TKR) compared with uncemented procedures. The aim of this study is to examine and compare the effects of cemented and uncemented TKR on the activation of selected markers of inflammation, endothelium, and coagulation, and on the activation of selected cytokines involved in the various aspects of the systemic response following surgery.

Methods

This was a single centre, prospective, case-control study. Following enrolment, blood samples were taken pre-operatively, and further samples were collected at day one and day seven post-operatively. One patient in the cemented group developed a deep-vein thrombosis confirmed on ultrasonography and was excluded, leaving 19 patients in this cohort (mean age 67.4, (sd 10.62)), and one patient in the uncemented group developed a post-operative wound infection and was excluded, leaving 19 patients (mean age 66.5, (sd 7.82)).


Bone & Joint Research
Vol. 3, Issue 3 | Pages 82 - 88
1 Mar 2014
Abdel MP Morrey ME Barlow JD Grill DE Kolbert CP An KN Steinmann SP Morrey BF Sanchez-Sotelo J

Objectives

The goal of this study was to determine whether intra-articular administration of the potentially anti-fibrotic agent decorin influences the expression of genes involved in the fibrotic cascade, and ultimately leads to less contracture, in an animal model.

Methods

A total of 18 rabbits underwent an operation on their right knees to form contractures. Six limbs in group 1 received four intra-articular injections of decorin; six limbs in group 2 received four intra-articular injections of bovine serum albumin (BSA) over eight days; six limbs in group 3 received no injections. The contracted limbs of rabbits in group 1 were biomechanically and genetically compared with the contracted limbs of rabbits in groups 2 and 3, with the use of a calibrated joint measuring device and custom microarray, respectively.


The Bone & Joint Journal
Vol. 95-B, Issue 3 | Pages 295 - 300
1 Mar 2013
Cawley DT Kelly N McGarry JP Shannon FJ

The optimum cementing technique for the tibial component in cemented primary total knee replacement (TKR) remains controversial. The technique of cementing, the volume of cement and the penetration are largely dependent on the operator, and hence large variations can occur. Clinical, experimental and computational studies have been performed, with conflicting results. Early implant migration is an indication of loosening. Aseptic loosening is the most common cause of failure in primary TKR and is the product of several factors. Sufficient penetration of cement has been shown to increase implant stability.

This review discusses the relevant literature regarding all aspects of the cementing of the tibial component at primary TKR.

Cite this article: Bone Joint J 2013;95-B:295–300.


Bone & Joint Research
Vol. 1, Issue 10 | Pages 238 - 244
1 Oct 2012
Naraoka T Ishibashi Y Tsuda E Yamamoto Y Kusumi T Kakizaki I Toh S

Objectives

This study aimed to investigate time-dependent gene expression of injured human anterior cruciate ligament (ACL), and to evaluate the histological changes of the ACL remnant in terms of cellular characterisation.

Methods

Injured human ACL tissues were harvested from 105 patients undergoing primary ACL reconstruction and divided into four phases based on the period from injury to surgery. Phase I was < three weeks, phase II was three to eight weeks, phase III was eight to 20 weeks, and phase IV was ≥ 21 weeks. Gene expressions of these tissues were analysed in each phase by quantitative real-time polymerase chain reaction using selected markers (collagen types 1 and 3, biglycan, decorin, α-smooth muscle actin, IL-6, TGF-β1, MMP-1, MMP-2 and TIMP-1). Immunohistochemical staining was also performed using primary antibodies against CD68, CD55, Stat3 and phosphorylated-Stat3 (P-Stat3).


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 8 | Pages 1065 - 1070
1 Aug 2011
Tanavalee A Honsawek S Rojpornpradit T Sakdinakiattikoon M Ngarmukos S

We compared inflammation in the knee after total knee replacement (TKR) for primary osteoarthritis between two groups of patients undergoing joint replacement with and without synovectomy. A total of 67 patients who underwent unilateral TKR were randomly divided into group I, TKR without synovectomy, and group II, TKR with synovectomy. Clinical outcomes, serial serum inflammatory markers (including interleukin-6 (IL-6), CRP and ESR) and the difference in temperature of the skin of the knee, compared with the contralateral side, were sequentially evaluated until 26 weeks after surgery.

Pre-operatively, there were no statistically different clinical parameters between groups I and II. At the 26-week follow-up, both groups had a similarly significantly improved American Knee Society clinical score (p < 0.001) and functional score (p < 0.001) with no differences between the groups. Similar changes in serial inflammatory markers were found in both groups, including mean peak levels of IL-6 (189 pg/ml (sd 53.4) versus 201 pg/ml (sd 49.4) for groups I and II, respectively) and CRP (91 mg/L (sd 24.1) versus 88 mg/L (sd 23.4), respectively) on the first post-operative day, returning to pre-operative values at two and six weeks, respectively. The mean peak level of ESR for the respective two groups was 46 mm/hr versus 48 mm/hr at two weeks, which had still not returned to its pre-operative mean value at 26 weeks. The elevation in the skin temperature appeared to mirror the peak elevation of the ESR, with a range of 2.5° C to 4.5° C with some reduction at 26 weeks but still exceeding the pre-operative value.

We concluded that synovectomy at the time of TKR does not provide any benefit to the clinical outcome or shorten the duration of the inflammatory response after surgery.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 2 | Pages 205 - 209
1 Feb 2011
Willis-Owen CA Keene GC Oakeshott RD

Metallosis is a rare cause of failure after total knee replacement and has only previously been reported when there has been abnormal metal-on-metal contact. We describe 14 patients (15 knees) whose total knee replacement required revision for a new type of early failure caused by extensive metallosis. A modification of a cementless rotating platform implant, which had previously had excellent long-term survival, had been used in each case. The change was in the form of a new porous-beaded surface on the femoral component to induce cementless fixation, which had been used successfully in the fixation of acetabular and tibial components. This modification appeared to have resulted in metallosis due to abrasive two-body wear. The component has subsequently been recalled and is no longer in use. The presentation, investigation, and findings at revision are described and a possible aetiology and its implications are discussed.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 12 | Pages 1575 - 1578
1 Dec 2009
Jaiswal PK Macmull S Bentley G Carrington RWJ Skinner JA Briggs TWR

Smoking is known to have an adverse effect on wound healing and musculoskeletal conditions. This case-controlled study looked at whether smoking has a deleterious effect in the outcome of autologous chondrocyte implantation for the treatment of full thickness chondral defects of the knee.

The mean Modified Cincinatti Knee score was statistically significantly lower in smokers (n = 48) than in non-smokers (n = 66) both before and after surgery (p < 0.05). Smokers experienced significantly less improvement in the knee score two years after surgery (p < 0.05). Graft failures were only seen in smokers (p = 0.016). There was a strong negative correlation between the number of cigarettes smoked and the outcome following surgery (Pearson’s correlation coefficient −0.65, p = 0.004).

These results suggest that patients who smoke have worse pre-operative function and obtain less benefit from this procedure than non-smokers. The counselling of patients undergoing autologous chondrocyte implantation should include smoking, not only as a general cardiopulmonary risk but also because poorer results can be expected in smokers following this procedure.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 12 | Pages 1585 - 1593
1 Dec 2008
Henricson A Linder L Nilsson KG

We compared the performance of uncemented trabecular metal tibial components in total knee replacement with that of cemented tibial components in patients younger than 60 years over two years using radiostereophotogrammetric analysis (RSA). A total of 22 consecutive patients (mean age 53 years, 33 to 59, 26 knees) received an uncemented NexGen trabecular metal cruciate-retaining monobloc tibial component and 19 (mean 53 years, 44 to 59, 21 knees) a cemented NexGen Option cruciate-retaining modular tibial component.

All the trabecular metal components migrated during the initial three months and then stabilised. The exception was external rotation, which did not stabilise until 12 months. Unlike conventional metal-backed implants which displayed a tilting migration comprising subsidence and lift-off from the tibial tray, most of the trabecular metal components showed subsidence only, probably due to the elasticity of the implant.

This pattern of subsidence is regarded as being beneficial for uncemented fixation.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 12 | Pages 1596 - 1602
1 Dec 2006
Muller SD Deehan DJ Holland JP Outterside SE Kirk LMG Gregg PJ McCaskie AW

The role of modular tibial implants in total knee replacement is not fully defined. We performed a prospective randomised controlled clinical trial using radiostereophotogrammetric analysis to compare the performance of an all-polyethylene tibia with a metal-backed cruciate-retaining condylar design, PFC-∑ total knee replacement for up to 24 months. There were 51 patients who were randomised into two treatment groups. There were 10 subsequent withdrawals, leaving 21 all-polyethylene and 20 metal-backed tibial implants. No patient was lost to follow-up. There were no significant demographic differences between the groups. At two years one metal-backed implant showed migration > 1 mm, but no polyethylene implant reached this level. There was a significant increase in the SF-12 and Oxford knee scores after operation in both groups.

In an uncomplicated primary total knee replacement the all-polyethylene PFC-∑ tibial prosthesis showed no statistical difference in migration from that of the metal-backed counterpart. There was no difference in the clinical results as assessed by the SF-12, the Oxford knee score, alignment or range of movement at 24 months, although these assessment measures were not statistically powered in this study.