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. 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

In a randomised prospective study, 20 patients with intra-articular fractures of the distal radius underwent arthroscopically- and fluoroscopically-assisted reduction and external fixation plus percutaneous pinning. Another group of 20 patients with the same fracture characteristics underwent fluoroscopically-assisted reduction alone and external fixation plus percutaneous pinning. The patients were evaluated clinically and radiologically at follow-up of 24 months. The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and modified Mayo wrist score were used at 3, 9, 12 and 24 months postoperatively. In the arthroscopically- and fluoroscopically-assisted group, triangular fibrocartilage complex tears were found in 12 patients (60%), complete or incomplete scapholunate ligament tears in nine (45%), and lunotriquetral ligament tears in four (20%). They were treated either arthroscopically or by open operation. Patients who underwent arthroscopically- and fluoroscopically-assisted treatment had significantly better supination, extension and flexion at all time points than those who had fluoroscopically-assisted surgery. The mean DASH scores were similar for both groups at 24 months, whereas the difference in the mean modified Mayo wrist scores remained statistically significant. Although the groups are small, it is clear that the addition of arthroscopy to the fluoroscopically-assisted treatment of intra-articular distal radius fractures improves the outcome. Better treatment of associated intra-articular injuries might also have been a reason for the improved outcome

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

The intra-articular injection of local anaesthetic is frequently used for pain relief after arthroscopy. There is, however, no published evidence of the analgesic effect of bupivacaine in the ankle. In a randomised, double-blind study, 35 patients undergoing arthroscopy of the ankle were allocated to receive intra-articular saline or bupivacaine. Pain was assessed using pain scores and additional analgesic requirements. Intra-articular bupivacaine had a significant analgesic effect in the immediate post-operative period, reducing pain scores and the need for additional analgesics. We recommend the use of intra-articular bupivacaine for post-operative analgesia in ankle surgery

Objectives. Sustained intra-articular delivery of pharmacological agents is an attractive modality but requires use of a safe carrier that would not induce cartilage damage or fibrosis. Collagen scaffolds are widely available and could be used intra-articularly, but no investigation has looked at the safety of collagen scaffolds within synovial joints. The aim of this study was to determine the safety of collagen scaffold implantation in a validated in vivo animal model of knee arthrofibrosis. Materials and Methods. A total of 96 rabbits were randomly and equally assigned to four different groups: arthrotomy alone; arthrotomy and collagen scaffold placement; contracture surgery; and contracture surgery and collagen scaffold placement. Animals were killed in equal numbers at 72 hours, two weeks, eight weeks, and 24 weeks. Joint contracture was measured, and cartilage and synovial samples underwent histological analysis. Results. Animals that underwent arthrotomy had equivalent joint contractures regardless of scaffold implantation (-13.9° versus -10.9°, equivalence limit 15°). Animals that underwent surgery to induce contracture did not demonstrate equivalent joint contractures with (41.8°) or without (53.9°) collagen scaffold implantation. Chondral damage occurred in similar rates with (11 of 48) and without (nine of 48) scaffold implantation. No significant difference in synovitis was noted between groups. Absorption of the collagen scaffold occurred within eight weeks in all animals. Conclusion. Our data suggest that intra-articular implantation of a collagen sponge does not induce synovitis or cartilage damage. Implantation in a native joint does not seem to induce contracture. Implantation of the collagen sponge in a rabbit knee model of contracture may decrease the severity of the contracture. Cite this article: J. A. Walker, T. J. Ewald, E. Lewallen, A. Van Wijnen, A. D. Hanssen, B. F. Morrey, M. E. Morrey, M. P. Abdel, J. Sanchez-Sotelo. Intra-articular implantation of collagen scaffold carriers is safe in both native and arthrofibrotic rabbit knee joints. Bone Joint Res 2016;6:162–171. DOI: 10.1302/2046-3758.63.BJR-2016-0193

Intra-articular resection of bone with soft-tissue balancing and total knee replacement (TKR) has been described for the treatment of patients with severe osteoarthritis of the knee associated with an ipsilateral malunited femoral fracture. However, the extent to which deformity in the sagittal plane can be corrected has not been addressed. We treated 12 patients with severe arthritis of the knee and an extra-articular malunion of the femur by TKR with intra-articular resection of bone and soft-tissue balancing. The femora had a mean varus deformity of 16° (8° to 23°) in the coronal plane. There were seven recurvatum deformities with a mean angulation of 11° (6° to 15°) and five antecurvatum deformities with a mean angulation of 12° (6° to 15°). The mean follow-up was 93 months (30 to 155). The median Knee Society knee and function scores improved from 18.7 (0 to 49) and 24.5 (10 to 50) points pre-operatively to 93 (83 to 100) and 90 (70 to 100) points at the time of the last follow-up, respectively. The mean mechanical axis of the knee improved from 22.6° of varus (15° to 27° pre-operatively to 1.5° of varus (3° of varus to 2° of valgus) at the last follow-up. The recurvatum deformities improved from a mean of 11° (6° to 15°) pre-operatively to 3° (0° to 6°) at the last follow-up. The antecurvatum deformities in the sagittal plane improved from a mean of 12° (6° to 16°) pre-operatively to 4.4° (0° to 8°) at the last follow-up. Apart from varus deformities, TKR with intra-articular bone resection effectively corrected the extra-articular deformity of the femur in the presence of antecurvatum of up to 16° and recurvatum of up to 15°

We reviewed 231 patients who had undergone total knee replacement with an AGC (Biomet) implant over a period of 2.5 years. After applying exclusion criteria and with some loss to follow-up, there were 144 patients available for study. These were divided into two groups; those who had received intra-articular steroid in the 11 months before surgery and those who had not. There were three deep infections, all of which occurred in patients who had received a steroid injection. The incidence of superficial infection was not significantly different in the two groups. Five patients had undergone investigation for suspected deep infection because of persistent swelling or pain and all of these had received an intra-articular injection pre-operatively. We conclude that the decision to administer intra-articular steroids to a patient who may be a candidate for total knee replacement should not be taken lightly because of a risk of post-operative deep infection

We carried out a retrospective review of 47 intra-articular fractures of the calcaneum treated by open reduction and internal fixation in 45 patients by a single surgeon between 1993 and 2001. The fractures were evaluated before operation by plain radiographs and a CT scan using Sanders’ classification. Osteosynthesis involved a lateral approach and the use of the AO calcaneal plate. The mean follow-up was for ten years (7 to 15). Clinical assessment included the American Orthopaedic Foot and Ankle Society Score (AOFAS), the Creighton-Nebraska Score, the Kerr, Prothero, Atkins Score and the SF-36 Health Questionnaire. The radiological evaluation consisted of lateral and axial views of the os calcis. Arthritic changes in the subtalar joint were assessed with an internal oblique view and were graded using the Morrey and Wiedeman scale. There were 18 excellent (38.3%), 17 good (36.2%), three fair (6.3%) and nine poor (19.2%) results. Five patients had a superficial wound infection and five others eventually had a subtalar arthrodesis because of continuing pain. Restoration of Böhler’s angle was associated with a better outcome. The degree of arthritic change in the subtalar joint did not correlate with the outcome scores or Sanders’ classification. Prompt osteosynthesis should be considered for intra-articular fractures of the calcaneum in order to restore the shape of the hindfoot and Böhler’s angle

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. Results. There was no statistical difference in the flexion contracture angles between those limbs that received intra-articular decorin versus those that received intra-articular BSA (66° vs 69°; p = 0.41). Likewise, there was no statistical difference between those limbs that received intra-articular decorin versus those who had no injection (66° vs 72°; p = 0.27). When compared with BSA, decorin led to a statistically significant increase in the mRNA expression of 12 genes (p < 0.01). In addition, there was a statistical change in the mRNA expression of three genes, when compared with those without injection. . Conclusions. In this model, when administered intra-articularly at eight weeks, 2 mg of decorin had no significant effect on joint contractures. However, our genetic analysis revealed a significant alteration in several fibrotic genes. Cite this article: Bone Joint Res 2014;3:82–8

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

We describe the results of 287 intra-articular fractures of the calcaneum in 247 patients treated by minimally-invasive reduction and K-wire fixation between 1994 and 2003. There were 210 men (85%) and 37 women (15%). The most common cause of injury was a fall from a height in 237 patients (96%). Fracture classification was based on the method described by Sanders and Essex-Lopresti. All patients were operated on within 21 days of injury and 89% (220) within 48 hours. The reduction was graded as nearly anatomical (less than 2 mm residual articular displacement and satisfactory overall alignment) in 212 (73.9%) fractures. There were 20 cases (7%) of superficial pin-track infection and five (1.7%) of deep infection. All healed at a mean of 6 weeks (3 to 19). Loss of reduction was observed in 13 fractures (4.5%) and a musculocutaneous flap was needed in three (1%). The results were evaluated in 176 patients (205 fractures) with a mean age of 44.3 years (13 to 67), available for follow-up at a mean of 43.4 months (25 to 87) using the Creighton-Nebraska Health Foundation Assessment score. The mean score was 83.9 points (63 to 100). There were 29 (16.5%) excellent, 98 (55.7%) good, 26 (14.8%) fair and 23 (13%) poor results. A total of 130 patients (73.9%) were able to return to their original occupation at a mean of 5.6 months (3.2 to 12.5) after the injury. Semi-open reduction and percutaneous fixation is an effective treatment for displaced intra-articular fractures of the calcaneum

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

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

1 . Criticisms are expressed of previous reports on the use of intra-articular injections in the treatment of osteoarthritis of the knee. 2. A series of 181 patients with primary osteoarthritis of the knee treated by certain intra-articular injections is reported. Three solutions in common use were studied; normal saline and mock injections served as controls. 3. Irrespective of the injection used, including the controls, no significant difference in the effects was demonstrated in the results. 4. The place of intra-articular injection therapy in osteoarthritis is discussed. Attention is drawn to the psychological implications

In order to clarify how intra-articular lesions influence the survival of a periacetabular osteotomy in patients with dysplasia of the hip, we performed an observational study of 121 patients (121 hips) who underwent a transposition osteotomy of the acetabulum combined with an arthroscopy. Their mean age was 40.2 years (13 to 64) and the mean follow-up was 9.9 years (2 to 18). Labral and cartilage degeneration tended to originate from the anterosuperior part of the acetabulum, followed by the femoral side. In all, eight hips (6.6%) had post-operative progression to Kellgren–Lawrence grade 4 changes, and these hips were associated with the following factors: moderate osteoarthritis, decreased width of the joint space, joint incongruity, and advanced intra-articular lesions (subchondral bone exposure in the cartilage and a full-thickness labral tear). Multivariate analysis indicated subchondral bone exposure on the femoral head as an independent risk factor for progression of osteoarthritis (p = 0.003). In hips with early stage osteoarthritis, femoral subchondral bone exposure was a risk factor for progression of the grade of osteoarthritis. . Although the outcome of transposition osteotomy of the acetabulum was satisfactory, post-operative progression of osteoarthritis occurred at a high rate in hips with advanced intra-articular lesions, particularly in those where the degenerative process had reached the point of femoral subchondral bone exposure

Aims. To present our experience of using a combination of intra-articular osteotomy and external fixation to treat different deformities of the knee. Patients and Methods. A total of six patients with a mean age of 26.5 years (15 to 50) with an abnormal hemi-joint line convergence angle (HJLCA) and mechanical axis deviation (MAD) were included. Elevation of a tibial hemiplateau or femoral condylar advancement was performed and limb lengthening with correction of residual deformity using a circular or monolateral Ilizarov frame. Results. At a mean follow-up of 2.8 years (1.5 to 4.1), the mean HJLCA improved from 15.6° (10° to 23°) pre-operatively to 0.4° (0° to 2°). The mean MAD improved from 70.0 mm (20.1 to 118.5) pre-operatively to 9.1 mm (3 to 15). The mean tibiofemoral angle improved from 31.0° (8° to 54°) pre-operatively to 4.9° (2° to 8°). The mean limb-length discrepancy decreased from 6.3 cm (2.9 to 13.6) pre-operatively to 1.1 cm (0 to 5). All osteotomies and distraction zones healed without complications. Conclusion. The use of intra-articular corrective osteotomies combined with the Ilizarov technique allowed correction of deformities of the knee joint with satisfactory HJLCA and overall mechanical axis in six patients with a good functional and cosmetic outcome in the short term. Cite this article: Bone Joint J 2017;99-B:204–10

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. Methods. A high-resolution small animal ultrasound system with a 40 MHz transducer was used for image-guided injections. A total of 36 guinea pigs were anaesthetised with isoflurane and placed on a heated stage. Sterile needles were inserted directly into the knee joint medially, while the transducer was placed on the lateral surface, allowing the femur, tibia and fat pad to be visualised in the images. B-mode cine loops were acquired during 100 µl. We assessed our ability to visualise 1) important anatomical landmarks, 2) the needle and 3) anatomical changes due to the injection. . Results. From the ultrasound images, we were able to visualise clearly the movement of anatomical landmarks in 75% of the injections. The majority of these showed separation of the fat pad (67.1%), suggesting the injections were correctly delivered in the joint space. We also observed dorsal joint expansion (23%) and patellar tendon movement (10%) in a smaller subset of injections. Conclusion. The results demonstrate that this image-guided technique can be used to visualise the location of an intra-articular injection in the joints of guinea pigs. Future studies using an ultrasound-guided approach could help improve the injection accuracy in a variety of anatomical locations and animal models, in the hope of developing anti-arthritic therapies. Cite this article: Bone Joint Res 2015;4:1–5

We carried out a prospective study in order to establish to what extent the intra-articular evaluation undertaken during arthroscopy of the knee differed between surgeons. Two senior specialist registrars and a consultant orthopaedic surgeon with a special interest in knee surgery were involved. A total of 78 knee arthroscopies (78 patients) was studied. Arthroscopy was first carried out by the trainee and then by the senior author (ACWH). The intra-articular evaluation during the arthroscopy was recorded independently by a third person in the operating theatre. Data were collected to record variations in examination under anaesthesia, the morphology and pathology of the menisci and anterior cruciate ligament and the state of the articular surfaces. The overall interobserver variation was 20% in all categories. We question the published results of intra-articular evaluation during knee arthroscopy when surgeons of different levels of experience are involved in a single study

We investigated 15 patients with painful hip arthroplasties using intra-articular injection of bupivicaine. Fourteen had pain relief and 13 of them were subsequently found to have loosening of one or both components. The relief of pain after total hip arthroplasty by intra-articular injection of bupivicaine indicates that a satisfactory result is probable after revision surgery with refixation of the components