Objectives. Recent studies have shown that systemic injection of rapamycin can prevent the development of osteoarthritis (OA)-like changes in human chondrocytes and reduce the severity of experimental OA. However, the systemic injection of rapamycin leads to many side effects. The purpose of this study was to determine the effects of intra-articular injection of Torin 1, which as a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin, on articular cartilage degeneration in a rabbit osteoarthritis model and to investigate the mechanism of Torin 1’s effects on experimental OA. Methods. Collagenase (type II) was injected twice into both knees of three-month-old rabbits to induce OA, combined with two intra–articular injections of Torin 1 (400 nM). Degeneration of articular cartilage was evaluated by histology using the Mankin scoring system at eight weeks after injection. Chondrocyte degeneration and autophagosomes were observed by transmission electron microscopy. Matrix metallopeptidase-13 (MMP-13) and vascular endothelial growth factor (VEGF) expression were analysed by quantitative RT-PCR (qPCR).Beclin-1 and light chain 3 (LC3) expression were examined by Western blotting. Results. Intra-articular injection of Torin 1 significantly reduced degeneration of the articular cartilage after induction of OA. Autophagosomes andBeclin-1 and LC3 expression were increased in the chondrocytes from Torin 1-treated rabbits. Torin 1 treatment also reduced MMP-13 and VEGF expression at eight weeks after collagenase injection. Conclusion. Our results demonstrate that intra-articular injection of Torin 1 reduces degeneration of articular cartilage in collagenase-induced OA, at least partially by autophagy activation, suggesting a novel therapeutic approach for preventing cartilage degeneration and treating OA. Cite this article: N-T. Cheng, A. Guo, Y-P. Cui. Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a rabbit osteoarthritis model. Bone Joint Res 2016;5:218–224. DOI: 10.1302/2046-3758.56.BJR-2015-0001

Aims. Intra-articular (IA) injection may be used when treating hip osteoarthritis (OA). Common injections include steroids, hyaluronic acid (HA), local anaesthetic, and platelet-rich plasma (PRP). Network meta-analysis allows for comparisons between two or more treatment groups and uses direct and indirect comparisons between interventions. This network meta-analysis aims to compare the efficacy of various IA injections used in the management of hip OA with a follow-up of up to six months. Methods. This systematic review and network meta-analysis used a Bayesian random-effects model to evaluate the direct and indirect comparisons among all treatment options. PubMed, Web of Science, Clinicaltrial.gov, EMBASE, MEDLINE, and the Cochrane Library were searched from inception to February 2023. Randomized controlled trials (RCTs) which evaluate the efficacy of HA, PRP, local anaesthetic, steroid, steroid+anaesthetic, HA+PRP, and physiological saline injection as a placebo, for patients with hip OA were included. Results. In this meta-analysis of 16 RCTs with a total of 1,735 participants, steroid injection was found to be significantly more effective than placebo injection on reported pain at three months, but no significant difference was observed at six months. Furthermore, steroid injection was considerably more effective than placebo injection for functional outcomes at three months, while the combination of HA+PRP injection was substantially more effective at six months. Conclusion. Evidence suggests that steroid injection is more effective than saline injection for the treatment of hip joint pain, and restoration of functional outcomes. Cite this article: Bone Joint J 2024;106-B(6):532–539

Aims. This study investigates the effects of intra-articular injection of adipose-derived mesenchymal stem cells (AdMSCs) and platelet-rich plasma (PRP) on lameness, pain, and quality of life in osteoarthritic canine patients. Methods. With informed owner consent, adipose tissue collected from adult dogs diagnosed with degenerative joint disease was enzymatically digested and cultured to passage 1. A small portion of cells (n = 4) surplus to clinical need were characterized using flow cytometry and tri-lineage differentiation. The impact and degree of osteoarthritis (OA) was assessed using the Liverpool Osteoarthritis in Dogs (LOAD) score, Modified Canine Osteoarthritis Staging Tool (mCOAST), kinetic gait analysis, and diagnostic imaging. Overall, 28 joints (25 dogs) were injected with autologous AdMSCs and PRP. The patients were followed up at two, four, eight, 12, and 24 weeks. Data were analyzed using two related-samples Wilcoxon signed-rank or Mann-Whitney U tests with statistical significance set at p < 0.05. Results. AdMSCs demonstrated stem cell-like characteristics. LOAD scores were significantly lower at week 4 compared with preinjection (p = 0.021). The mCOAST improved significantly after three months (p = 0.001) and six months (p = 0.001). Asymmmetry indices decreased from four weeks post-injection and remained significantly lower at six months (p = 0.025). Conclusion. These improvements in quality of life, reduction in pain on examination, and improved symmetry in dogs injected with AdMSCs and PRP support the effectiveness of this combined treatment for symptom modification in canine OA for six months. Cite this article: Bone Joint Res 2021;10(10):650–658

Total Knee Arthroplasty (TKA) improves the quality of life of osteoarthritic and rheumatoid arthritis patients, however, is associated with moderate to severe postoperative pain. There are multiple methods of managing postoperative pain that include epidural anesthesia but it prevents early mobilization and results in postoperative hypotension and spinal infection. Controlling local pain pathways through intra-articular administration of analgesics is a novel method and is inexpensive and simple. Hence, we assess the effects of postoperative epidural bupivacaine injection along with intra-articular injection in total knee replacement patients. The methodology included 100 patients undergoing TKA randomly divided into two groups, one administered with only epidural bupivacaine injection and the other with intra-articular cocktail injection. The results were measured based on a 10-point pain assessment scale, knee's range of motion (ROM), and Lysholm knee score. The VAS score was lower in the intra-articular cocktail group compared to the bupivacaine injection group until the end of 1-week post-administration (p<0.01). Among inter-group comparisons, we observed that the range of motion was significantly more in cocktail injection as compared to the bupivacaine group till the end of one week (p<0.05). Lysholm's score was significantly more in cocktail injection as compared to the bupivacaine group till the end of one week (p<0.05). Our study showed that both epidural bupivacaine injection and intra-articular injection were effective in reducing pain after TKA and have a comparable functional outcome at the end of 4 weeks follow up. However, the pain relief was faster in cases with intra-articular injection, providing the opportunity for early rehabilitation. Thus, we recommend the use of intra-articular cocktail injection for postoperative management of pain after total knee arthroplasty, which enables early rehabilitation and faster functional recovery of these patients

Aims. There is conflicting evidence on the safety of intra-articular injections of hyaluronic acid (HA) or corticosteroids (CSs) before total knee arthroplasty (TKA). We performed a meta-analysis of the relationship between intra-articular injections and subsequent infection rates after TKA. Methods. We searched PubMed, EMBASE, and the Cochrane Library for cohort studies that assessed the effect of preoperative injection of drugs into the joint cavity on the infection rate after TKA. The outcomes analyzed included the total infection rate, as well as those for different preoperative injection time periods and different drugs. Results. Eight studies, including 73,880 in the injection group and 126,187 in the control group, met the inclusion criteria. The injection group had a significantly higher postoperative infection rate than the control group (risk ratio (RR) 1.16; 95% confidence interval (CI) 1.07 to 1.27; p < 0.001; I. 2. = 32%). For patients who received injections up to three months preoperatively, the postoperative infection risk was significantly higher than that in the control group (RR 1.26; 95% CI 1.18 to 1.35; p＜0.001; I. 2. = 0%). There was no significant difference in the infection rates between the four-to-six-month injection and control groups (RR 1.12; 95% CI 0.93 to 1.35; p = 0.240; I. 2. = 75%) or between the seven-to-12-month injection and control groups (RR 1.02; 95% CI 0.94 to 1.12; p = 0.600; I. 2. = 0%). Conclusion. Current evidence suggests that intra-articular injections of CSs or HA before TKA increase the risk of postoperative infection. Injections administered more than three months before TKA do not significantly increase the risk of infection. Cite this article: Bone Joint Res 2022;11(3):171–179

Aims. Recent studies have suggested that corticosteroid injections into the knee may harm the joint resulting in cartilage loss and possibly accelerating the progression of osteoarthritis (OA). The aim of this study was to assess whether patients with, or at risk of developing, symptomatic osteoarthritis of the knee who receive intra-articular corticosteroid injections have an increased risk of requiring arthroplasty. Methods. We used data from the Osteoarthritis Initiative (OAI), a multicentre observational cohort study that followed 4,796 patients with, or at risk of developing, osteoarthritis of the knee on an annual basis with follow-up available up to nine years. Increased risk for symptomatic OA was defined as frequent knee symptoms (pain, aching, or stiffness) without radiological evidence of OA and two or more risk factors, while OA was defined by the presence of both femoral osteophytes and frequent symptoms in one or both knees. Missing data were imputed with multiple imputations using chained equations. Time-dependent propensity score matching was performed to match patients at the time of receving their first injection with controls. The effect of corticosteroid injections on the rate of subsequent (total and partial) knee arthroplasty was estimated using Cox proportional-hazards survival analyses. Results. After removing patients lost to follow-up, 3,822 patients remained in the study. A total of 249 (31.3%) of the 796 patients who received corticosteroid injections, and 152 (5.0%) of the 3,026 who did not, had knee arthroplasty. In the matched cohort, Cox proportional-hazards regression resulted in a hazard ratio of 1.57 (95% confidence interval (CI) 1.37 to 1.81; p < 0.001) and each injection increased the absolute risk of arthroplasty by 9.4% at nine years’ follow-up compared with those who did not receive injections. Conclusion. Corticosteroid injections seem to be associated with an increased risk of knee arthroplasty in patients with, or at risk of developing, symptomatic OA of the knee. These findings suggest that a conservative approach regarding the treatment of these patients with corticosteroid injections should be recommended. Cite this article: Bone Joint J 2020;102-B(5):586–592

Intra-articular punctures and injections are performed routinely on patients with injuries to and chronic diseases of joints, to release an effusion or haemarthrosis, or to inject drugs. The purpose of this study was to investigate the accuracy of placement of the needle during this procedure. A total of 76 cadaver acromioclavicular joints were injected with a solution containing methyl blue and subsequently dissected to distinguish intra- from peri-articular injection. In order to assess the importance of experience in achieving accurate placement, half of the injections were performed by an inexperienced resident and half by a skilled specialist. The specialist injected a further 20 cadaver acromioclavicular joints with the aid of an image intensifier. The overall frequency of peri-articular injection was much higher than expected at 43% (33 of 76) overall, with 42% (16 of 38) by the specialist and 45% (17 of 38) by the resident. The specialist entered the joint in all 20 cases when using the image intensifier. Correct positioning of the needle in the joint should be facilitated by fluoroscopy, thereby guaranteeing an intra-articular injection

To investigate the significance of a cluster of cases of glenohumeral chondrolysis occuring following the intra-articular injection of methylene blue to assess rotator cuff integrity during open anterior acromioplasty. All cases of acromioplasty during the period 1999 to 2004 were reviewed to determine the incidence of chondrolysis with and without methylene blue injection. There was a significantly higher incidence of chondrolysis following intra-articular injection of methylene blue. The association of intra-articular methylene blue with chondrolysis has not been previously described in the literature. We conclude that methylene blue should not be used for intra-articular injection

Intra-articular injections of steroid into the hip are used for a variety of reasons in current orthopaedic practice. Recently their safety prior to ipsilateral total hip replacement has been called into question owing to concerns about deep joint infection. We undertook a retrospective analysis of all patients who had undergone local anaesthetic and steroid injections followed by ipsilateral total hip replacement over a five-year period. Members of the surgical team, using a lateral approach to the hip, performed all the injections in the operating theatre using a strict aseptic technique. The mean time between injection and total hip replacement was 18 months (4 to 50). The mean follow-up after hip replacement was 25.8 months (9 to 78), during which time no case of deep joint sepsis was found. In our series, ipsilateral local anaesthetic and steroid injections have not conferred an increased risk of infection in total hip replacement. We believe that the practice of intra-articular local anaesthetic and steroid injections to the hip followed by total hip replacement is safer than previously reported

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

Introduction. Total knee arthroplasty [TKA] is a common procedure to relieve painful disability from advanced knee arthritis. However, related blood loss, ranging from 800 to 1200 ml, increase risk and disruption of recovery in anemic patients following TKA. Various methods for blood conservation had been proposed and examined. In the literature, the intra-articular administration of a solution mixing bupivacaine and epinephrine was commonly used after knee surgeries. Therefore, we conducted a retrospective, case controlled review of our primary TKAs to determine the hemostatic efficacy of this regimen following TKAs. Material and Methods. Over a period of 12 months, 135 eligible patients were divided two groups simply according to the intra-articular injection or not: a control group (N=63) and a treatment group (N=72). In the treatment group, a 40 ml vial of 0.5% bupivacaine with epinephrine 1: 200000 was given prior to the deflation of pneumatic tourniquet. No drainage was used in all TKAs. Without recordable drainage, a Gross formula, considering gender and body composition, was used for estimate blood loss following TKAs. In addition, serial changes in hemoglobin as well as the requirement of allogenic transfusion were also compared between groups. Results. The mean calculated blood loss in the treatment group was 650.4 +/− 257.1 ml, compared to 648.8+/− 222.1 ml in the control group (p=0.9). Similar decrease in hemoglobin as well as rates of allogenic transfusion needs were observed between groups.[2.5+/− 0.9 g/dl vs. 2.4+/− 0.8 g/dl; 13.9% vs. 12.7%, respectively]. Discussion and Conclusion. Although local analgesics mixing vasoconstrictive agents seem a logic solution to save blood loss and relieve pain simultaneously, the hypothesis that intra-articular injection of bupivacaine and epinephrine would save blood and even transfusion needs following TKAs is not supported by various bleeding parameters in this study. In addition to temporary benefit in pain relief, this regimen only has little effect on blood conservation. Therefore, new regimen as well as hemostatic means are still required and explored to reduce blood loss following TKAs

Osteoarthritis (OA) is a degenerative and inflammatory joint disease that affects the whole joint. Mesenchymal stem cells ability to secrete anti-inflammatory and immuno-modulatory factors represents an attractive tool in the treatment of OA. Considering the risk of cell leakage and the massive cell death upon intra-articular injection, we developed a micromolding protocol of encapsulation that allows to obtain particles that (i) could be injected with a 26G needle into a mouse joint and (ii) could provide a 3D microenvironment supporting cell biological activity. Polydimethylsiloxane (PDMS) chips containing circular micromolds were manufactured and a solution of alginate (2% w/v) containing human adipose stem cells (3 millions/mL) was deposited on the chips. Cell loading into the micromolds was performed either by sedimentation or by centrifugation. Following Ca2+ crosslinking, alginate particles (diameter 150±0.7μm) were obtained. The number of cells per particle was 5 times higher when the micromolds were loaded by centrifugation. Cell number and metabolic activity remained stable for 7 days after encapsulation and injection through a 26G needle had no impact on cell viability. When cells were stimulated with TNF-alpha and INF-gamma, prostaglandin E2 (PGE2) concentration in the supernatant was multiplied by 13 and 7 and indoleamine2,3-dioxygenase (IDO) activity was 2 and 4 times higher when cell loading was performed by sedimentation or centrifugation, respectively. We have demonstrated that encapsulated cells were able to sense and respond to an inflammatory stimulus and their therapeutic potential will be evaluated in a murine model of osteoarthritis

The administration of intra-articular local anaesthetic is common following arthroscopy of the knee. However, recent evidence has suggested that bupivacaine may be harmful to articular cartilage. This study aimed to establish whether infiltration of bupivacaine around the portals is as effective as intra-articular injection. We randomised 137 patients to receive either 20 ml 0.5% bupivacaine introduced into the joint (group 1) or 20 ml 0.5% bupivacaine infiltrated only around the portals (group 2) following arthroscopy. A visual analogue scale was administered one hour post-operatively to assess pain relief. Both patients and observers were blinded to the treatment group. A power calculation was performed. The mean visual analogue score was 3.24 (. sd. 2.20) in group I and 3.04 (. sd. 2.31) in group 2. This difference was not statistically significant (p = 0.62). Infiltration of bupivacaine around the portals had an equivalent effect on pain scores at one hour, and we would therefore recommend this technique to avoid the possible chondrotoxic effect of intra-articular bupivacaine

Introduction and Aims: Adequacy of post-operative pain control can effect total knee arthroplasty (TKA) outcomes. We examine the effectiveness of a simple and inexpensive method using long-acting local anesthetic (bupivacaine) with epinephrine and morphine injection on controlling pain, blood loss, and motion in primary TKA. Method: We retrospectively reviewed 170 patients who underwent 208 primary TKA, by a single surgeon between October 2001 and December 2002. The control group of 75 patients (99 knees) had received no intra-operative injections. The study group of 95 patients (109 knees) had received intra-operative injection of 0.25 percent bupivacane with epinephrine and morphine divided two-thirds soft-tissue injection and one-third intra-articular injection. Bilateral simultaneous TKA in the study group received a divided anaesthetic dose. Results: The control group required significantly more breakthrough narcotic (85 percent vs 67 percent; p=0.004); and required more narcotic reversal for over-sedation. The study group had significantly higher ROM at discharge 63 degrees vs 52 degrees. Lower ROM at discharge was associated with manipulation (p equals 0.001). The study group required less transfused blood (mean 0.03 vs 0.1 units), and had significantly lower bleeding indices 2.7 vs 3.5. Conclusion: Preemptive analgesia with intra-articular and soft-tissue injection of long-acting local anesthetic with epinephrine and morphine appears to decrease need for rescue narcotics and reversal agents. The use of the injection also increases ROM at discharge, which reduces the need for manipulation. Lastly, the bleeding index and transfusion requirements are significantly reduced. This inexpensive method is effective in improving the post-operative course of primary TKA

Introduction and Objective. Osteoarthritis (OA) is the most common inflammatory and degenerative joint disease. Mesenchymal Stromal Cells (MSCs), with their chondro-protective and immune-regulatory properties, have been considered as a new approach to treat OA. Considering the risk of cell leakage outside the articular space and the poor survival rate after intra-articular (IA) injection, we hypothesized that cell encapsulation in cytoprotective hydrogels could overcome these limitations and provide cells with a suitable 3D microenvironment supporting their biological activity. We previously generated micromolded alginate particles (diameter 150 μm) and demonstrated the long-term viability of microencapsulated MSCs isolated from human adipose tissue (hASCs). Encapsulated cells maintained their in vitro ability to sense and respond to a pro-inflammatory environment (IFN-γ/TNF-α or synovial fluids from OA patients) by secreting PGE. 2. , IDO, HGF and TGF-β. In this study, we evaluated the anti-OA efficacy of these microencapsulated hASCs in a post-traumatic OA model in rabbits. Materials and Methods. OA was surgically induced by anterior cruciate ligament transection (ACLT)-mediated destabilization of the right knee in rabbits (n=24). Eight weeks after surgery, destabilized joints were injected (IA, 26G needle) with 200 μL of either PBS, blank microparticles, non-encapsulated or microencapsulated cells (5×10. 5. cells). Six weeks after injection, rabbits were euthanized and all destabilized (right) and sham-operated (left contralateral) joints were dissected and analyzed for OA severity. Tibial subchondral bone histomorphometric parameters were measured by quantitative micro-computed tomography (micro-CT). Histological sections of samples were analyzed after Safranin-O staining and quantitatively assessed according to a modified Osteoarthritis Research Society International (OARSI) scoring system. Immunohistochemical detection of NITEGE was performed to assess the extracellular matrix degradation. Results. Micro-CT analysis of destabilized joints confirmed that the rabbit ACLT significantly affected the tibial subchondral bone architecture as early as eight weeks, as revealed by significant changes of the subchondral bone parameters of operated joints compared to the sham operated joints. In particular, destabilized joints exhibited a Bone Volume/Tissue Volume ratio (BV/TV) ranging from 53.4% to 56.6%, compared to a mean BV/TV of 65.4% for sham operated joints. All destabilized joints also exhibited a significantly increased modified OARSI score, ranging from 7.4±0.4 for those injected with encapsulated cells to 8.9±0.2 for those injected with PBS, as compared to 4.8±0.4 for sham-operated joints. Of interest, we identified a slight, while not significant, reduction of the severity of OA lesions after injection of microencapsulated cells using the modified OARSI scoring. Finally, semi-quantitative analysis of NITEGE immunostaining revealed a significant increase in all destabilized joints that were injected with PBS or blank microparticles, in comparison with sham ones. On the contrary, NITEGE immunostaining in destabilized joints that were injected with non-encapsulated or encapsulated hASC revealed a significant reduced NITEGE immunostaining, indicating a decreased matrix degradation. Conclusions. Our data suggest that the microencapsulated hASCs exerted their anti-OA properties after IA injection in rabbit knees, as evidenced by the tendency toward a reduced modified OARSI score, and most importantly a significant reduction in NITEGE immunostaining associated matrix degradation. Further studies are now warranted to investigate the anti-OA efficacy of microencapsulated hASCs in the long-term

Introduction. Liposomal bupivacaine has been shown to be effective in managing post-operative pain in hallux valgus and hemorrhoid surgery. However, non-industry-supported and well-powered randomized studies evaluating its efficacy in Total Knee Arthroplasty (TKA) are lacking. Our hypothesis was that liposomal bupivacaine would not decrease post-operative visual analog pain scores (VAS) or narcotic consumption in the acute post-operative period. Methodology. Two hundred seven consecutive patients were enrolled into a single-blinded prospective randomized study. We included patients undergoing unilateral TKA by five fellowship-trained surgeons with a diagnosis of osteoarthritis, rheumatoid arthritis, or post-traumatic arthritis. Patients were excluded for any other diagnosis necessitating TKA, allergy to the medications, or pre-operative opiate use. Participants received standardized pain management, anesthesia, and physical therapy. Patients were randomized intra-operatively to one of three groups: an intra-articular (IA) injection of bupivacaine and morphine at the conclusion of the procedure, a peri-articular (PA) injection of a bupivacaine and morphine, or a PA injection of liposomal bupivacaine. Post-operative pain VAS and mean morphine equivalents (MME) consumed were recorded and compared utilizing analysis of variance (ANOVA). A power analysis demonstrated that 159 patients were needed for 80% power to detect a 25% difference in VAS or MME. Results. Patients in each study group had a mean VAS score of 3.95 (SD 2.1), 3.97 (SD 1.9). and 3.86 (SD 1.8) (p=0.94), respectively. MME consumed per day in each group was 100.7 (SD 48.4), 100.1 (SD 42.2), and 98.9 (SD 41.6) (p=0.97). Conclusion. Liposomal bupivacaine does not alter mean pain scores or post-operative narcotic consumption in patients undergoing unilateral TKA. Further, no difference was noted in comparing patients who received a single IA injection versus a PA injection. To our knowledge, this is the first reported study to evaluate post-operative pain control between identical IA and PA injections in patients undergoing unilateral TKA

Objective

Dunkin Hartley guinea pigs, a commonly used animal model of osteoarthritis, were used to determine if high frequency ultrasound can ensure intra-articular injections are accurately positioned in the knee joint.

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. Results. The accuracy of injection in the US and blind groups was 100% (45/45) and 71.1% (32/45), respectively; this difference was significant (p < 0.001). Both groups had significant improvements in VAS pain score, ASES score, SSV, forward flexion, abduction, external rotation, and internal rotation throughout follow-up until 12 weeks after injection (all p < 0.001). There were no significant differences between the VAS pain scores, the ASES score, the SSV and all ROMs between the two groups at the time points assessed (all p > 0.05). No injection-related adverse effects were noted in either group. Conclusion. We found no significant differences in pain and functional outcomes between the two groups, although an US-guided injection was associated with greater accuracy. Considering that it is both costly and time-consuming, an US-guided intra-articular injection of corticosteroid seems not always to be necessary in the treatment of FS as it gives similar outcomes as a blind injection. Cite this article: Bone Joint J 2021;103-B(2):353–359

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. Results. The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined media. MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC and suppressed MIA-induced synovitis, accompanied by the recovery of cartilage matrix. Pharmacological inhibitors of PEDF receptor (PEDFR) and signal transducer and activator of transcription 3 (STAT3) signalling substantially blocked the chondrogenic promoting activity of 29-mer on the cultured BM-MSCs and injured AC. Conclusion. The 29-mer/HA formulation effectively induces chondrocyte regeneration and formation of cartilage matrix in the damaged AC. Cite this article: Bone Joint Res 2024;13(4):137–148

Aims. Knee osteoarthritis (OA) is characterized by a chronic inflammatory process involving multiple cytokine pathways, leading to articular cartilage degeneration. Intra-articular therapies using pharmaceutical or autologous anti-inflammatory factors offer potential non-surgical treatment options. Autologous protein solution (APS) is one such product that uses the patient’s blood to produce a concentrate of cells and anti-inflammatory cytokines. This study evaluated the effect of a specific APS intra-articular injection (nSTRIDE) on patient-reported outcome measures compared to saline in moderate knee OA. Methods. A parallel, double-blinded, placebo-controlled randomized controlled trial was conducted, where patients with unilateral moderate knee OA (Kellgren-Lawrence grade 2 or 3) received either nSTRIDE or saline (placebo) injection to their symptomatic knee. The primary outcome was the difference in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score at 12 months post-intervention. Secondary outcomes included WOMAC component scores, Knee injury and Osteoarthritis Outcome Score (KOOS), and visual analogue scale (VAS) scores at all follow-up timepoints (three, six, and 12 months). Results. A total of 40 patients were analyzed (21 nSTRIDE; 19 saline) in the study. No significant difference was found between nSTRIDE and saline groups for WOMAC total score at 12 months (mean difference -10.4 (95% CI -24.4 to 3.6; p = 0.141). There were no significant differences in WOMAC or KOOS scores across all timepoints. VAS scores favoured the saline group for both rest and worst pain scales at 12 months post-injection (mean difference (worst) 12 months 21.5 (95% CI 6.2 to 36.8; p = 0.008); mean difference (rest) 12 months 17.8 (95% CI 2.2 to 33.4; p = 0.026)). There were no adverse events recorded in either study group. Conclusion. Our study demonstrates no significant differences between nSTRIDE and saline groups in KOOS and WOMAC scores over time. Notably, APS injection resulted in significantly worse pain symptoms at 12 months compared to saline injection. Cite this article: Bone Joint J 2024;106-B(9):907–915