The majority of patients with osteoarthritis present to orthopaedic surgeons seeking relief of pain and associated restoration of function. Although our understanding of the physiology of pain has improved greatly over the last 25 years there remain a number of unexplained pain-related observations in patients with osteoarthritis. The understanding of pain in osteoarthritis, its modulation and treatment is central to orthopaedic clinical practice and in this annotation we explore some of the current concepts applicable. We also introduce the concept of the ‘phantom joint’ as a cause for persistent pain after joint replacement

Objectives. Our objective in this article is to test the hypothesis that type 2 diabetes mellitus (T2DM) is a factor in the onset and progression of osteoarthritis, and to characterise the quality of the articular cartilage in an appropriate rat model. Methods. T2DM rats were obtained from the UC Davis group and compared with control Lewis rats. The diabetic rats were sacrificed at ages from six to 12 months, while control rats were sacrificed at six months only. Osteoarthritis severity was determined via histology in four knee quadrants using the OARSI scoring guide. Immunohistochemical staining was also performed as a secondary form of osteoarthritic analysis. Results. T2DM rats had higher mean osteoarthritis scores than the control rats in each of the four areas that were analysed. However, only the results at the medial and lateral femur and medial tibia were significant. Cysts were also found in T2DM rats at the junction of the articular cartilage and subchondral bone. Immunohistochemical analysis does not show an increase in collagen II between control and T2DM rats. Mass comparisons also showed a significant relationship between mass and osteoarthritis score. Conclusions. T2DM was found to cause global degeneration in the UCD rat knee joints, suggesting that diabetes itself is a factor in the onset and progression of osteoarthritis. The immunohistochemistry stains showed little to no change in collagen II degeneration between T2DM and control rats. Overall, it seems that the animal model used is pertinent to future studies of T2DM in the development and progression of osteoarthritis. Cite this article: Bone Joint Res 2014;3:203–11

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. The modified Dunn procedure has the potential to restore the anatomy in hips with severe slipped capital femoral epiphyses (SCFE). However, there is a risk of developing avascular necrosis of the femoral head (AVN). In this paper, we report on clinical outcome, radiological outcome, AVN rate and complications, and the cumulative survivorship at long-term follow-up in patients undergoing the modified Dunn procedure for severe SCFE. Patients and Methods. We performed a retrospective analysis involving 46 hips in 46 patients treated with a modified Dunn procedure for severe SCFE (slip angle > 60°) between 1999 and 2016. At nine-year-follow-up, 40 hips were available for clinical and radiological examination. Mean preoperative age was 13 years, and 14 hips (30%) presented with unstable slips. Mean preoperative slip angle was 64°. Kaplan–Meier survivorship was calculated. Results. At the latest follow-up, the mean Merle d’Aubigné and Postel score was 17 points (14 to 18), mean modified Harris Hip Score was 94 points (66 to 100), and mean Hip Disability and Osteoarthritis Outcome Score was 91 points (67 to 100). Postoperative slip angle was 7° (1° to 16°). One hip (2%) had progression of osteoarthritis (OA). Two hips (5%) developed AVN of the femoral head and required further surgery. Three other hips (7%) underwent implant revision due to screw breakage or change of wires. Cumulative survivorship was 86% at ten-year follow-up. Conclusion. The modified Dunn procedure for severe SCFE resulted in a low rate of AVN, low risk of progression to OA, and high functional scores at long-term follow-up. The slip deformities were mainly corrected but secondary impingement deformities can develop in some hips and may require further surgical treatment. Cite this article: Bone Joint J 2019;101-B:403–414

The purpose of this study was to evaluate the effect of various non-operative modalities of treatment (transcutaneous electrical nerve stimulation (TENS); neuromuscular electrical stimulation (NMES); insoles and bracing) on the pain of osteoarthritis (OA) of the knee. . We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify the therapeutic options which are commonly adopted for the management of osteoarthritis (OA) of the knee. The outcome measurement tools used in the different studies were the visual analogue scale and The Western Ontario and McMaster Universities Arthritis Index pain index: all pain scores were converted to a 100-point scale. . A total of 30 studies met our inclusion criteria: 13 on insoles, seven on TENS, six on NMES, and four on bracing. The standardised mean difference (SMD) in pain after treatment with TENS was 1.796, which represented a significant reduction in pain. The significant overall effect estimate for NMES on pain was similar to that of TENS, with a SMD of 1.924. The overall effect estimate of insoles on pain was a SMD of 0.992. The overall effect of bracing showed a significant reduction in pain of 1.34. . Overall, all four non-operative modalities of treatment were found to have a significant effect on the reduction of pain in OA of the knee. . This study shows that non-operative physical modalities of treatment are of benefit when treating OA of the knee. However, much of the literature reviewed evaluates studies with follow-up of less than six months: future work should aim to evaluate patients with longer follow-up. Cite this article: Bone Joint J 2016;98-B(1 Suppl A):89–94

Aims. The aim of this study was to evaluate the clinical and radiological outcome of using an anatomical short-stem shoulder prosthesis to treat primary osteoarthritis of the glenohumeral joint. Patients and Methods. A total of 66 patients (67 shoulders) with a mean age of 76 years (63 to 92) were available for clinical and radiological follow-up at two different timepoints (T1, mean 2.6 years, . sd. 0.5; T2, mean 5.3 years,. sd. 0.7). Postoperative radiographs were analyzed for stem angle, cortical contact, and filling ratio of the stem. Follow-up radiographs were analyzed for timing and location of bone adaptation (cortical bone narrowing, osteopenia, spot welds, and condensation lines). The bone adaptation was classified as low (between zero and three features of bone remodelling around the humeral stem) or high (four or more features). Results. The mean Constant score improved significantly from 28.5 (. sd. 11.6) preoperatively to 75.5 (. sd. 8.5) at T1 (p < 0.001) and remained stable over time (T2: 76.6, . sd. 10.2). No stem loosening was seen. High bone adaptation was present in 42% of shoulders at T1, with a slight decrease to 37% at T2. Cortical bone narrowing and osteopenia in the region of the calcar decreased from 76% to 66% between T1 and T2. Patients with high bone adaptation had a significantly higher mean filling ratio of the stem at the metaphysis (0.60, . sd. 0.05 vs 0.55, . sd. 0.06; p = 0.003) and at the diaphysis (0.65 . sd. 0.05 vs 0.60 . sd. 0.05; p = 0.007). Cortical contact of the stem was also associated with high bone adaptation (14/25 shoulders, p = 0.001). The clinical outcome was not influenced by the radiological changes. Conclusion. Total shoulder arthroplasty using a short-stem humeral component resulted in good clinical outcomes with no evidence of loosening. However, approximately 40% of the shoulders developed substantial bone loss in the proximal humerus at between four and seven years of follow-up. Cite this article: Bone Joint J 2018;100-B:603–9

Objectives. Salubrinal is a synthetic agent that elevates phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) and alleviates stress to the endoplasmic reticulum. Previously, we reported that in chondrocytes, Salubrinal attenuates expression and activity of matrix metalloproteinase 13 (MMP13) through downregulating nuclear factor kappa B (NFκB) signalling. We herein examine whether Salubrinal prevents the degradation of articular cartilage in a mouse model of osteoarthritis (OA). Methods. OA was surgically induced in the left knee of female mice. Animal groups included age-matched sham control, OA placebo, and OA treated with Salubrinal or Guanabenz. Three weeks after the induction of OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At three and six weeks, the femora and tibiae were isolated and the sagittal sections were stained with Safranin O. Results. Salubrinal suppressed the progression of OA by downregulating p-NFκB p65 and MMP13. Although Guanabenz elevates the phosphorylation level of eIF2α, it did not suppress the progression of OA. Conclusions. Administration of Salubrinal has chondroprotective effects in arthritic joints. Salubrinal can be considered as a potential therapeutic agent for alleviating symptoms of OA. Cite this article: Bone Joint Res 2015;4:84–92

We have undertaken a prospective clinical and radiological analysis of 124 shoulder arthroplasties (113 patients) carried out for osteoarthritis. The clinical results showed improvement in the absolute Constant score and the American Shoulder and Elbow Surgeons score of 22 and 43, respectively. Both were statistically significant (p < 0.001). There was no significant difference in the scores after hemiarthroplasty and total arthroplasty in those patients with an intact rotator cuff. When revision was used as the end-point for survival at ten years, survival of 86%, or 90% if glenoid components made of Hylamer sterilised in air were omitted, was obtained in primary osteoarthritis. The most common cause for revision in the hemiarthroplasty group was glenoid pain at a mean of 1.5 years; in the total arthroplasty group it was loosening of the glenoid at a mean of 4.5 years. Analysis of pre-operative factors showed that the risk of gross loosening of the glenoid increased threefold when there was evidence of erosion of the glenoid at operation. Shoulder arthroplasty should not be delayed once symptomatic osteoarthritis has been established and should be undertaken before failure of the cuff or erosion of the glenoid are present

Aims. The aim of this study was to compare the Push Ortho Thumb Brace CMC and a custom-made orthosis in the treatment of patients with primary osteoarthritis of the carpometacarpal joint of the thumb. Our outcome measures were pain scores, tests of hand function, patient satisfaction and patient preference. Patients and Methods. A multicentre crossover randomised controlled trial was conducted which included 63 patients (44 women) with primary osteoarthritis of the carpometacarpal joint of the thumb. Of these, 59 patients with a mean age of 60.1 years (standard deviation 8.2), completed the study. Patients used both orthoses for two weeks with a two-week washout period in-between. Pain was measured on a 10-cm visual analogue scale. Hand function was assessed using the Jebsen Taylor Hand Function test, Nine Hole Peg Test, key grip, pinch grip and Functional Index for Hand Osteoarthritis. Patient preference was assessed using the Dutch version of the Quebec User Evaluation of Satisfaction with Assistive Technology score. Results. Both orthoses resulted in a minor reduction in pain scores without significant difference between the two orthoses. The Push Ortho Thumb Brace CMC interfered less with key grip (p < 0.001) and the Nine Hole Peg Test (p < 0.001) than the custom-made orthosis. The Push Ortho Thumb Brace CMC had a higher patient satisfaction (p < 0.001) and most patients preferred this orthosis for future use. Conclusion. When considering an orthosis for osteoarthritis of the carpometacarpal joint of the thumb, patients may prefer the Push Ortho Thumb Brace CMC. Cite this article: Bone Joint J 2017;99-B:237–44

Thoracic back pain caused by osteoarthritis of a single costovertebral joint is a poorly recognised condition. We report a series of five patients who were successfully treated by resection arthroplasty of this joint. Each had received a preliminary image-guided injection of local anaesthetic and steroid into the joint to confirm it as the source of pain. The surgical technique is described. There were no complications. The pain improved from a mean of 7.0 (6 to 8) on a visual analogue scale to 2.0 (0 to 4) post-operatively. The final post-operative Oswestry disability index was a mean of 19.4 (9 to 38). Isolated osteoarthritis of a costovertebral joint is a rare but treatable cause of thoracic back pain. It is possible to obtain excellent short- and intermediate-term relief from pain with resection arthroplasty in appropriately selected patients

Deformity of the proximal femur in fibrous dysplasia leads to deviation of the mechanical axis of the hip, which may lead to the development of secondary osteoarthritis (OA). This study investigated the prevalence and predisposing factors for the development of OA in patients with fibrous dysplasia of the proximal femur. We reviewed the records of 209 patients from our institutional database with fibrous dysplasia of the proximal femur, investigating possible predisposing factors including patient demographics, the extent of the coxa vara deformity, the presence of peri-articular disease, and the overall burden of skeletal disease. Of the 209 patients, 24 (12%) had radiological evidence of OA in the ipsilateral hip. The prevalence was significantly higher in patients with polyostotic fibrous dysplasia compared with those with monostotic disease (p < 0.001). In a subgroup analysis of patients with polyostotic disease, the extent of deformity (quantified using the neck–shaft angle), and the presence of peri-articular disease (whether in the head of the femur or the acetabulum) were significant predictors of osteoarthritis (neck–shaft angle likelihood ratio (LR) = 0.847 per 1° increase, p = 0.004; presence of lesion in the head of the femur LR = 9.947, p = 0.027; presence of lesion in the acetabulum LR = 11.231, p = 0.014). . Our data suggest that patients with polyostotic fibrous dysplasia have a high risk of developing secondary OA of the hips. This risk is higher in patients with peri-articular disease, and those with a more severe deformity of proximal femur. Cite this article: Bone Joint J 2015;97-B:1007–11

Aims. Recently, there has been considerable interest in quantifying the associations between bony abnormalities around and in the hip joint and osteoarthritis (OA). Our aim was to investigate the relationships between acetabular undercoverage, acetabular overcoverage, and femoroacetabular impingement (FAI) with OA of the hip, which currently remain controversial. . Materials and Methods. A total of 545 cadaveric skeletons (1090 hips) from the Hamann-Todd osteological collection were obtained. Femoral head volume (FHV), acetabular volume (AV), the FHV/AV ratio, acetabular version, alpha angle and anterior femoral neck offset (AFNO) were measured. A validated grading system was used to quantify OA of the hip as minimal, moderate, or severe. Multiple linear and multinomial logistic regression were used to determine the factors that correlated independently with the FHV, AV, and the FHV/AV ratio. . Results. Female cadavers had smaller FHVs (standardised beta -0.382, p < 0.001), and AVs (standardised beta -0.351, p < 0.001), compared with male patients, although the FHV/AV ratio was unchanged. Every 1° increase in alpha angle increased the probability of having moderate OA of the hip compared with minimal OA by 7.1%. Every 1 mm decrease in AFNO increased the probability of having severe or moderate OA of the hip, compared with minimal OA, by 11% and 9%, respectively. The relative risk ratios of having severe OA of the hip compared with minimal OA were 7.2 and 3.3 times greater for acetabular undercoverage and overcoverage, respectively, relative to normal acetabular cover. . Conclusion . Acetabular undercoverage and overcoverage were independent predictors of increased OA of the hip. The alpha angle and AFNO had modest effects, supporting the hypothesis that bony abnormalities both in acetabular dysplasia and FAI are associated with severe OA. Cite this article: Bone Joint J 2017;99-B:432–9

Objectives. The purpose of this study was to assess N-acetyl aspartate changes in the thalamus in patients with osteoarthritis of the hip using proton magnetic resonance spectroscopy. Methods. Nine patients with osteoarthritis of the hip (symptomatic group, nine women; mean age 61.4 years (48 to 78)) and nine healthy volunteers (control group, six men, three women; mean age 30.0 years (26 to 38)) underwent proton magnetic resonance spectroscopy to assess the changes of N-acetyl aspartate in the thalamus. . Results. The ratio of N-acetyl aspartate to creatine plus phosphocreatine in the thalamus contralateral to the symptomatic hip in patients with osteoarthritis of the hip was significantly lower than the ratio of N-acetyl aspartate to creatine plus phosphocreatine in the thalamus in the control group (1.611 (1.194 to 1.882) vs 1.355 (1.043 to 1.502), p < 0.001). And, a strong negative correlation was detected between the ratio of N-acetyl aspartate to creatine plus phosphocreatine in the thalamus contralateral to the symptomatic hip in patients with osteoarthritis of the hip and pain duration (r = -0.83, p = 0.018). Conclusions. We evaluated the ratio of N-acetyl aspartate to creatine plus phosphocreatine in the thalamus of patients with osteoarthritis of the hip by using proton magnetic resonance spectroscopy. We concluded that the ratio of N-acetyl aspartate to creatine plus phosphocreatine in the thalamus contralateral to the symptomatic hip in patients with osteoarthritis of the hip were significantly lower than those in the thalamus of the control group, and that pain duration was strongly related to the decrease of the ratio of N-acetyl aspartate to creatine plus phosphocreatine

Introduction. Osteoarthritis (OA) is a progressively debilitating disease that affects mostly cartilage, with associated changes in the bone. The increasing incidence of OA and an ageing population, coupled with insufficient therapeutic choices, has led to focus on the potential of stem cells as a novel strategy for cartilage repair. Methods. In this study, we used scaffold-free mesenchymal stem cells (MSCs) obtained from bone marrow in an experimental animal model of OA by direct intra-articular injection. MSCs were isolated from 2.8 kg white New Zealand rabbits. There were ten in the study group and ten in the control group. OA was induced by unilateral transection of the anterior cruciate ligament of the knee joint. At 12 weeks post-operatively, a single dose of 1 million cells suspended in 1 ml of medium was delivered to the injured knee by direct intra-articular injection. The control group received 1 ml of medium without cells. The knees were examined at 16 and 20 weeks following surgery. Repair was investigated radiologically, grossly and histologically using haematoxylin and eosin, Safranin-O and toluidine blue staining. Results. Radiological assessment confirmed development of OA changes after 12 weeks. Rabbits receiving MSCs showed a lower degree of cartilage degeneration, osteophyte formation, and subchondral sclerosis than the control group at 20 weeks post-operatively. The quality of cartilage was significantly better in the cell-treated group compared with the control group after 20 weeks. Conclusions. Bone marrow-derived MSCs could be promising cell sources for the treatment of OA. Neither stem cell culture nor scaffolds are absolutely necessary for a favourable outcome. Cite this article: Bone Joint Res 2014;3:32–7

Objectives. Subtotal or total meniscectomy in the medial or lateral compartment of the knee results in a high risk of future osteoarthritis. Meniscal allograft transplantation has been performed for over thirty years with the scientifically plausible hypothesis that it functions in a similar way to a native meniscus. It is thought that a meniscal allograft transplant has a chondroprotective effect, reducing symptoms and the long-term risk of osteoarthritis. However, this hypothesis has never been tested in a high-quality study on human participants. This study aims to address this shortfall by performing a pilot randomised controlled trial within the context of a comprehensive cohort study design. Methods. Patients will be randomised to receive either meniscal transplant or a non-operative, personalised knee therapy program. MRIs will be performed every four months for one year. The primary endpoint is the mean change in cartilage volume in the weight-bearing area of the knee at one year post intervention. Secondary outcome measures include the mean change in cartilage thickness, T2 maps, patient-reported outcome measures, health economics assessment and complications. Results. This study is expected to report its findings in 2016. Cite this article: Bone Joint Res 2015;4:93–8

Aims

To compare time dependent functional improvement for patients with medial, respectively lateral knee osteoarthritis (OA) after treatment with opening wedge osteotomy relieving the pressure on the osteoarthritic part of the knee.

We retrospectively assessed the value of identifying impinging osteophytes using dynamic computer simulation of CT scans of the elbow in assisting their arthroscopic removal in patients with osteoarthritis of the elbow. A total of 20 patients were treated (19 men and one woman, mean age 38 years (19 to 55)) and followed for a mean of 25 months (24 to 29). We located the impinging osteophytes dynamically using computerised three-dimensional models of the elbow based on CT data in three positions of flexion of the elbow. These were then removed arthroscopically and a capsular release was performed. The mean loss of extension improved from 23° (10° to 45°) pre-operatively to 9° (0° to 25°) post-operatively, and the mean flexion improved from 121° (80° to 140°) pre-operatively to 130° (110° to 145°) post-operatively. The mean Mayo Elbow Performance Score improved from 62 (30 to 85) to 95 (70 to 100) post-operatively. All patients had pain in the elbow pre-operatively which disappeared or decreased post-operatively. According to their Mayo scores, 14 patients had an excellent clinical outcome and six a good outcome; 15 were very satisfied and five were satisfied with their post-operative outcome. We recommend this technique in the surgical management of patients with osteoarthritis of the elbow. Cite this article: Bone Joint J 2014;96-B:237–41

We report a study of 112 patients with primary anteromedial osteoarthritis of the knee and their families. Sibling risk was determined using randomly selected single siblings. Spouses were used as controls. The presence of symptomatic osteoarthritis was determined using an Oxford knee score of ≥ 29 supported by a Kellgren and Lawrence radiological score of II or greater. Using Fisher’s exact test we found that there was a significant increased risk of anteromedial osteoarthritis (OA) relative to the control group (p = 0.031). The recurrence risk of anteromedial OA to siblings was 3.21 (95% confidence interval 1.12 to 9.27). These findings imply that genetic factors may play a major role in the development of anteromedial OA of the knee

This is a retrospective review of the results of the Acclaim total elbow replacement in 11 older patients aged ≥ 65 years with primary osteoarthritis of the elbow, with a mean follow-up of 57.6 months (30 to 86.4). Significant reductions in pain and improvement in range of movement and function were recorded. Radiological review revealed two patients with 1 mm lucencies in a single zone, and one patient with 1 mm lucencies in two zones. No components required revision. There were no deep infections, dislocations or mechanical failures. Complications included one intra-operative medial condylar fracture and one post-operative transient ulnar neuropathy, which resolved. This study demonstrates that the Acclaim prosthesis provides good symptomatic relief and improvement of function in patients with primary osteoarthritis, with low rates of loosening or other complications. This prosthesis can therefore be considered for patients aged ≥ 65 years with primary osteoarthritis of the elbow

We evaluated the short-term of 0 to 90 days and the longer term, up to 12.7 years, mortality for patients undergoing primary total hip replacement (THR) in Denmark in comparison to the general population. Through the Danish Hip Arthroplasty Registry we identified all primary THRs undertaken for osteoarthritis between 1 January 1995 and 31 December 2006. Each patient (n = 44 558) was matched at the time of surgery with three people from the general population (n = 133 674). We estimated mortality rates and mortality rate ratios with 95% confidence intervals for THR patients compared with the general population. There was a one-month period of increased mortality immediately after surgery among THR patients, but overall short-term mortality (0 to 90 days) was significantly lower (mortality rate ratio 0.8; 95% confidence interval 0.7 to 0.9). However, THR surgery was associated with increased short-term mortality in subjects under 60 years old, and among THR patients without comorbidity. Long-term mortality was lower among THR patients than in controls (mortality rate ratio 0.7; 95% confidence interval 0.7 to 0.7). Overall, THR was associated with lower short- and long-term mortality among patients with osteoarthritis. Younger patients and patients without comorbidity before surgery may also experience increased mortality after THR surgery, although the absolute risk of death is small