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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 99 - 99
14 Nov 2024
Umrath F Liang C Jud S Alexander D Danalache M
Full Access

Introduction. Osteoarthritis (OA) often results from joint misloading, which affects chondrocyte calcium signaling through mechano-sensitive receptors such as Piezo1, -2, and TRPV4. Activation of Piezo1, especially under inflammatory conditions, can trigger premature chondrocyte apoptosis. Intra-articular glucocorticoid therapy, while beneficial against inflammation and pain in osteoarthritis, may induce oxidative stress and chondrotoxicity at higher doses. This study aims to assess the effects of glucocorticoids, particularly triamcinolone, on chondrocyte elasticity and mechanosignaling. Method. Chondrocytes isolated from articular condyles obtained from patients undergoing knee replacement surgery (n= 5) were cultured for 7 days in triamcinolone acetonide (TA) at different concentrations (0.2µM – 2mM). Cytoskeletal changes were assessed by F-actin labeling. Cell elasticity was measured using atomic force microscopy (AFM). Labeling cells (n=6 patients) with the calcium-sensitive dye (Fluo-4) enabled monitoring changes in intracellular calcium fluorescence intensity during guided single-cell mechanical indentation (500 nN) by AFM. Result. Cell exposure to 2 mM TA led to cell death and crystallization of TA in the cell culture media. However, the concentration of TA for intra-articular application is 46 times higher at 92.1 mM (40 mg/ml). The maximal pharmacological effect on viable cells was observed at 0.2 mM. AFM results showed a significant decrease of elasticity (p<0.001), alongside significantly higher calcium intensities both prior to and during mechanical stimulation in the TA-treated samples (p<0.05). Conclusion. Administration of TA significantly impacts the mechanical properties of chondrocytes, reducing cellular elasticity while simultaneously enhancing calcium-dependent mechanosensitivity. This data suggests a correlation between glucocorticoid-induced changes in cell elasticity and cell mechanosensitivity. Finding ways to minimize the effect of glucocorticoids on cell mechanosensitivity could help to make future therapies safer and reduce side effects


In osteoarthritis, chondrocytes acquire a hypertrophic phenotype that contributes to matrix degradation. Inflammation is proposed as trigger for the shift to a hypertrophic phenotype. Using in vitro culture of human chondrocytes and cartilage explants we could not find evidence for a role of inflammatory signalling activation. We found, however, that tissue repair macrophages may contribute to the onset of hypertrophy (doi: 10.1177/19476035211021907) Intra-articularly injected triamcinolone acetonide to inhibit inflammation in a murine model of collagenase-induced osteoarthritis, increased synovial macrophage numbers and osteophytosis, confirming the role of macrophages in chondrocyte hypertrophy occurring in osteophyte formation (doi: 10.1111/bph.15780). In search of targets to inhibit chondrocyte hypertrophy, we combined existing microarray data of different cartilage layers of murine growth plate and murine articular cartilage after induction of collagenase-induced osteoarthritis. We identified common differentially expressed genes and selected those known to be associated to inflammation. This revealed EPHA2, a tyrosine kinase receptor, as a new target. Using in silico, in vitro and in vivo models we demonstrated that inhibition of EPHA2 might be a promising treatment for osteoarthritis. Recently, single cell RNA-seq. has revealed detailed information about different populations of chondrocytes in articular cartilage during osteoarthritis. We re-analysed a published scRNA-seq data set of healthy and osteoarthritic cartilage to obtain the differentially expressed genes in the population of hypertrophic chondrocytes compared to the other chondrocytes, applied pathway analyses and then used drug databases to search for upstream inhibitors of these pathways. This drug repurposing approach led to the selection of 6 drugs that were screened and tested using several in vitro models with human chondrocytes and cartilage explants. In this lecture I will present this sequence of studies to highlight different approaches and models that can be used in the quest for a disease modifying drug for osteoarthritis


The Bone & Joint Journal
Vol. 104-B, Issue 10 | Pages 1142 - 1147
3 Oct 2022
van den Berg C van der Zwaard B Halperin J van der Heijden B

Aims

The aim of this retrospective study was to evaluate the rate of conversion to surgical release after a steroid injection in patients with a trigger finger, and to analyze which patient- and trigger finger-related factors affect the outcome of an injection.

Methods

The medical records of 500 patients (754 fingers) treated for one or more trigger fingers with a steroid injection or with surgical release, between 1 January 2016 and 1 April 2020 with a follow-up of 12 months, were analyzed. Conversion to surgical release was recorded as an unsuccessful treatment after an injection. The effect of patient- and trigger finger-related characteristics on the outcome of an injection was assessed using stepwise manual backward multivariate logistic regression analysis.


Bone & Joint 360
Vol. 10, Issue 3 | Pages 35 - 37
1 Jun 2021


Bone & Joint 360
Vol. 10, Issue 2 | Pages 26 - 28
1 Apr 2021


Bone & Joint 360
Vol. 10, Issue 1 | Pages 28 - 31
1 Feb 2021


The Bone & Joint Journal
Vol. 103-B, Issue 2 | Pages 353 - 359
1 Feb 2021
Cho C Min B Bae K Lee K Kim DH

Aims

Ultrasound (US)-guided injections are widely used in patients with conditions of the shoulder in order to improve their accuracy. However, the clinical efficacy of US-guided injections compared with blind injections remains controversial. The aim of this study was to compare the accuracy and efficacy of US-guided compared with blind corticosteroid injections into the glenohumeral joint in patients with primary frozen shoulder (FS).

Methods

Intra-articular corticosteroid injections were administered to 90 patients primary FS, who were randomly assigned to either an US-guided (n = 45) or a blind technique (n = 45), by a shoulder specialist. Immediately after injection, fluoroscopic images were obtained to assess the accuracy of the injection. The outcome was assessed using a visual analogue scale (VAS) for pain, the American Shoulder and Elbow Surgeons (ASES) score, the subjective shoulder value (SSV) and range of movement (ROM) for all patients at the time of presentation and at three, six, and 12 weeks after injection.


The Bone & Joint Journal
Vol. 102-B, Issue 5 | Pages 600 - 605
1 May 2020
Parker S Riley N Dean B

Aims

Base of thumb osteoarthritis (BTOA) is a common age-related disease which has a significant negative impact upon quality of life. Our aim was to assess current UK practice in secondary care with regard to the nature of non-surgical treatments, the surgical procedures most commonly performed, and factors influencing the surgical decision-making process.

Methods

Ten consecutive patients undergoing surgery for BTOA between March 2017 and May 2019 were prospectively identified in 15 UK centres. Demographic details, duration of symptoms, radiological grade, non-surgical management strategies, and surgery conducted were recorded. A supplementary consultant questionnaire consisting of four multiple-choice-questions (MCQ) based on hypothetical clinical scenarios was distributed.


The Bone & Joint Journal
Vol. 102-B, Issue 5 | Pages 606 - 610
1 May 2020
Nicholson JA Slader B Martindale A Mckie S Robinson CM

Aims

The primary aim of this study was to evaluate the efficacy of distension arthrography in the treatment of adhesive capsulitis of the shoulder. The secondary aim was to assess which patient and procedural factors predicted the recurrence of symptoms after the procedure.

Methods

All patients referred to our shoulder clinic over a ten-year period, between 2008 and 2018, with a clinical diagnosis of capsulitis and symptoms persisting for more than six months, were offered treatment with a distension arthrogram. All procedures were performed by one of five musculoskeletal radiologists, with a combination of steroid, local anaesthetic, and a distention volume of 10 ml, 30 ml, or 50 ml. Patient demographics, procedural details, recurrence of symptoms, and the need for further intervention were evaluated.


Bone & Joint Research
Vol. 8, Issue 2 | Pages 41 - 48
1 Feb 2019
Busse P Vater C Stiehler M Nowotny J Kasten P Bretschneider H Goodman SB Gelinsky M Zwingenberger S

Objectives. Intra-articular injections of local anaesthetics (LA), glucocorticoids (GC), or hyaluronic acid (HA) are used to treat osteoarthritis (OA). Contrast agents (CA) are needed to prove successful intra-articular injection or aspiration, or to visualize articular structures dynamically during fluoroscopy. Tranexamic acid (TA) is used to control haemostasis and prevent excessive intra-articular bleeding. Despite their common usage, little is known about the cytotoxicity of common drugs injected into joints. Thus, the aim of our study was to investigate the effects of LA, GC, HA, CA, and TA on the viability of primary human chondrocytes and tenocytes in vitro. Methods. Human chondrocytes and tenocytes were cultured in a medium with three different drug dilutions (1:2; 1:10; 1:100). The following drugs were used to investigate cytotoxicity: lidocaine hydrochloride 1%; bupivacaine 0.5%; triamcinolone acetonide; dexamethasone 21-palmitate; TA; iodine contrast media; HA; and distilled water. Normal saline served as a control. After an incubation period of 24 hours, cell numbers and morphology were assessed. Results. Using LA or GC, especially triamcinolone acetonide, a dilution of 1:100 resulted in only a moderate reduction of viability, while a dilution of 1:10 showed significantly fewer cell counts. TA and CA reduced viability significantly at a dilution of 1:2. Higher dilutions did not affect viability. Notably, HA showed no effects of cytotoxicity in all drug dilutions. Conclusion. The toxicity of common intra-articular injectable drugs, assessed by cell viability, is mainly dependent on the dilution of the drug being tested. LA are particularly toxic, whereas HA did not affect cell viability. Cite this article: P. Busse, C. Vater, M. Stiehler, J. Nowotny, P. Kasten, H. Bretschneider, S. B. Goodman, M. Gelinsky, S. Zwingenberger. Cytotoxicity of drugs injected into joints in orthopaedics. Bone Joint Res 2019;8:41–48. DOI: 10.1302/2046-3758.82.BJR-2018-0099.R1


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_15 | Pages 21 - 21
1 Nov 2018
Capar S van Osch G Verhaar J Bastiaansen-Jenniskens Y
Full Access

Joint injuries often result in inflammation and cartilage defects. When inflamed, the synovium secretes factors that prevent successful cartilage repair by inhibiting chondrogenic differentiation of progenitor cells. In particular the pro-inflammatory macrophages in the synovium are indicated to contribute to this anti-chondrogenic effect. Thus, we aimed to counteract the anti-chondrogenic effect of inflamed synovium by modulating synovial inflammation and its macrophages. Synovium tissue obtained from osteoarthritic patients undergoing a total knee replacement was cut into explants and cultured for 72 hours +/− 1 µM of the anti-inflammatory drug triamcinolone acetonide (TAA) (Sigma Aldrich). TAA significantly decreased gene expression of TNFA, IL1β and IL6, and increased expression of CCL18, IL1RA in synovial explants (all with p < 0.001). On the other hand, TAA significantly decreased the percentages of pro-inflammatory CD14+/CD80+ and CD14+/CD86+ macrophages in the synovium (both p < 0.001) as assessed by flow cytometry analyses. The percentages of anti-inflammatory CD14+/CD163+ macrophages, is significantly increased (p < 0.001) in TAA treated synovium. Conditioned medium (CM) from synovium explants downregulated the gene expression of cartilage matrix components collagen type-2 and aggrecan expression in chondrogenic MSCs. This chondrogenesis inhibiting effect was reduced by treating synovium with TAA during the production of the CM. Our findings indicate that reducing synovial inflammation might improve the joint environment for better cartilage repair, possibly by modulation of macrophage phenotypes


The Bone & Joint Journal
Vol. 100-B, Issue 9 | Pages 1138 - 1145
1 Sep 2018
Soreide E Murad MH Denbeigh JM Lewallen EA Dudakovic A Nordsletten L van Wijnen AJ Kakar S

Aims

Dupuytren’s contracture is a benign, myoproliferative condition affecting the palmar fascia that results in progressive contractures of the fingers. Despite increased knowledge of the cellular and connective tissue changes involved, neither a cure nor an optimum form of treatment exists. The aim of this systematic review was to summarize the best available evidence on the management of this condition.

Materials and Methods

A comprehensive database search for randomized controlled trials (RCTs) was performed until August 2017. We studied RCTs comparing open fasciectomy with percutaneous needle aponeurotomy (PNA), collagenase clostridium histolyticum (CCH) with placebo, and CCH with PNA, in addition to adjuvant treatments aiming to improve the outcome of open fasciectomy. A total of 20 studies, involving 1584 patients, were included.


Bone & Joint 360
Vol. 7, Issue 4 | Pages 15 - 17
1 Aug 2018


Aims

The aim of this study was to compare the efficacy of a corticosteroid injection for the treatment of carpal tunnel syndrome (CTS) in patients with and without Raynaud’s phenomenon.

Patients and Methods

In a prospective study, 139 patients with CTS were treated with a corticosteroid injection (10 mg triamcinolone acetonide); 34 had Raynaud’s phenomenon and 105 did not (control group). Grip strength, perception of touch with a Semmes-Weinstein monofilament and the Boston Carpal Tunnel Questionnaires (BCTQ) were assessed at baseline and at six, 12 and 24 weeks after the injection. The Cold Intolerance Severity Score (CISS) questionnaire was also assessed at baseline and 24 weeks after the injection.


Bone & Joint Research
Vol. 5, Issue 12 | Pages 602 - 609
1 Dec 2016
Muto T Kokubu T Mifune Y Inui A Sakata R Harada Y Takase F Kurosaka M

Objectives. Triamcinolone acetonide (TA) is widely used for the treatment of rotator cuff injury because of its anti-inflammatory properties. However, TA can also produce deleterious effects such as tendon degeneration or rupture. These harmful effects could be prevented by the addition of platelet-rich plasma (PRP), however, the anti-inflammatory and anti-degenerative effects of the combined use of TA and PRP have not yet been made clear. The objective of this study was to determine how the combination of TA and PRP might influence the inflammation and degeneration of the rotator cuff by examining rotator cuff-derived cells induced by interleukin (IL)-1ß. Methods. Rotator cuff-derived cells were seeded under inflammatory stimulation conditions (with serum-free medium with 1 ng/ml IL-1ß for three hours), and then cultured in different media: serum-free (control group), serum-free + TA (0.1mg/ml) (TA group), serum-free + 10% PRP (PRP group), and serum-free + TA (0.1mg/ml) + 10% PRP (TA+PRP group). Cell morphology, cell viability, and expression of inflammatory and degenerative mediators were assessed. Results. Exposure to TA significantly decreased cell viability and changed the cell morphology; these effects were prevented by the simultaneous administration of PRP. Compared with the control group, expression levels of inflammatory genes and reactive oxygen species production were reduced in the TA, PRP, and TA+PRP groups. PRP significantly decreased the expression levels of degenerative marker genes. Conclusions. The combination of TA plus PRP exerts anti-inflammatory and anti-degenerative effects on rotator cuff-derived cells stimulated by IL-1ß. This combination has the potential to relieve the symptoms of rotator cuff injury. Cite this article: T. Muto, T. Kokubu, Y. Mifune, A. Inui, R. Sakata, Y. Harada, F. Takase, M. Kurosaka. Effects of platelet-rich plasma and triamcinolone acetonide on interleukin-1ß-stimulated human rotator cuff-derived cells. Bone Joint Res 2016;5:602–609. DOI: 10.1302/2046-3758.512.2000582


Bone & Joint 360
Vol. 5, Issue 5 | Pages 34 - 35
1 Oct 2016


The Bone & Joint Journal
Vol. 98-B, Issue 8 | Pages 1027 - 1035
1 Aug 2016
Pereira LC Kerr J Jolles BM

Aims

Using a systematic review, we investigated whether there is an increased risk of post-operative infection in patients who have received an intra-articular corticosteroid injection to the hip for osteoarthritis prior to total hip arthroplasty (THA).

Methods

Studies dealing with an intra-articular corticosteroid injection to the hip and infection following subsequent THA were identified from databases for the period between 1990 to 2013. Retrieved articles were independently assessed for their methodological quality.


Bone & Joint 360
Vol. 5, Issue 4 | Pages 23 - 25
1 Aug 2016


The Bone & Joint Journal
Vol. 98-B, Issue 4 | Pages 498 - 503
1 Apr 2016
Mahadevan D Attwal M Bhatt R Bhatia M

Aims. The objective of this double-blind randomised controlled trial was to assess whether ultrasound guidance improved the efficacy of corticosteroid injections for Morton’s neuroma (MN). . Patients and Methods. In all, 50 feet (40 patients) were recruited for this study but five feet were excluded due to the patients declining further participation. The mean age of the remaining 36 patients (45 feet) was 57.8 years (standard deviation (. sd. ) 12.9) with a female preponderance (33F:12M). All patients were followed-up for 12 months. Treatment was randomised to an ultrasound guided (Group A) or non-ultrasound guided (Group B) injection of 40 mg triamcinolone acetonide and 2 ml 1% lignocaine, following ultrasound confirmation of the diagnosis. . Results. The mean visual analogue score for pain improved significantly in both groups (Group A – from 64 mm, . sd. 25 mm to 29 mm, . sd. 27; Group B – from 69 mm, . sd. 23 mm to 37 mm, . sd. 25) with no statistical difference between them at all time-points. The failure rate within 12 months of treatment was 11/23 (48%) and 12/22 (55%) in Groups A and B, respectively (p = 0.458). The improvement in Manchester Oxford Foot Questionnaire Index and patient satisfaction favoured Group A in the short-term (three months) that almost reached statistical significance (p = 0.059 and 0.066 respectively). However, this difference was not observed beyond three months. . Conclusion. This study has shown that ultrasound guidance did not demonstrably improve the efficacy of corticosteroid injections in patients with MN. Take home message: In the presence of a clear diagnosis of MN, a trained clinician who understands the forefoot anatomy may perform an injection without ultrasound guidance with good and safe results. Cite this article: Bone Joint J 2016;98-B:498–503


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_15 | Pages 21 - 21
1 Dec 2015
Nijsse B Kadic L De Waal Malefijt M Schreurs B
Full Access

Local infiltration analgesia (LIA) is promoted as an effective treatment modality for pain control after total knee arthroplasty (TKA) (1). A mixture of drugs is used to provide a multimodal analgesic effect. Previous studies reported that the use of these drugs is safe. After we carefully implemented a LIA study protocol in our practice, concerns raised about patient safety with probably higher infection rates. This forced us to perform an interim analysis after the first 58 cases. 58 patients underwent a unilateral TKA with a standardised LIA protocol (2), which consisted of a mixture of ropivacaine, epinephrine, and triamcinolone acetonide. Complications, knee function and patient satisfaction scores were prospectively recorded during regular outpatient control. Four patients (6.9%) presented with signs of periprosthetic joint infection (PJI) within two months after surgery. Baseline characteristics were similar between the infected and non infected group. All infections were treated with debridement and retention, and antimicrobial treatment was started. One patient who suffered an infection died during followup. At two years followup all implants could be retained. Knee function and KSS score were acceptable for the patients who suffered PJI. There is no consensus on the combination of drugs used for LIA. The application of corticosteroids in LIA is reported to be safe (3), but arguable results about the injection of local corticosteroids around knee arthroplasty surgery in the past have raised suspicion in literature (4). Combined with our unacceptable high rate of PJI, we believe that the current body of evidence, with small heterogeneous series, does not support the safe use of corticosteroids in LIA