Objectives. This study looked to analyse the expression levels of microRNA-140-3p and microRNA-140-5p in synovial fluid, and their correlations to the severity of disease regarding knee osteoarthritis (OA). Methods. Knee joint synovial fluid samples were collected from 45 patients with OA of the knee (15 mild, 15 moderate and 15 severe), ten healthy volunteers, ten patients with gouty arthritis, and ten with rheumatoid arthritis. The Kellgren–Lawrence grading (KLG) was used to assess the radiological severity of knee OA, and the patients were stratified into mild (KLG < 2), moderate (KLG = 2), and severe (KLG > 2). The expression of miR-140-3p and miR-140-5p of individual samples was measured by SYBR Green quantitative polymerase chain reaction (PCR) analysis. The expression of miR-140-3p and miR-140-5p was normalised to U6 internal control using the 2. -△△CT. method. All data were processed using SPSS software. Results. Expression of both miR-140-3p and miR-140-5p was downregulated in OA synovial fluid, showing a statistical difference between the OA and non-OA group, and increased OA severity was associated with a decreased expression of miR-140-3p or miR-140-5p. The Spearman rank correlation analysis suggested that the expression of miR-140-3p or miR-140-5p was negatively correlated with OA severity. In addition, the expression of miR-140-5p was 7.4 times higher than that of miR-140-3p across all groups. Conclusion. The dysregulation of miR-140-3p and miR-140-5p in synovial fluid and their correlations with the disease severity of OA may provide an important experimental basis for OA classification, and the miR-140-3p/miR-140-5p are of great potential as biomarkers in the diagnosis and clinical management of patients with OA. Cite this article: C-M. Yin, W-C-W. Suen, S. Lin, X-M. Wu, G. Li, X-H. Pan. Dysregulation of both miR-140-3p and miR-140-5p in synovial fluid correlate with osteoarthritis severity. Bone Joint Res 2017;6:612–618. DOI: 10.1302/2046-3758.611.BJR-2017-0090.R1

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

1. In fifteen patients with unilateral osteoarthritis of the hip bilateral measurements of the intraosseous pressure of the femoral neck and determination of femoral vein pressure were done simultaneously. These pressure examinations were followed by bilateral intraosseous phlebography of the proximal part of the femur. 2. In a second series of fifteen patients the intraosseous pressures of the femoral head and neck were measured simultaneously before operation for osteoarthritis. 3. The pressure in the femoral vein was equal on the two sides. The intraosseous pressure in the femoral neck was always higher in the arthritic hip than on the unaffected side. In hips with osteoarthritis the pressure in the femoral head was higher than the pressure in the neck. 4. Intraosseous phlebography indicated a state of intramedullary venous engorgement in osteoarthritis. The normal channels for venous drainage from the femoral head and neck were not visible in the phlebographs from the arthritic side. Instead, drainage took place through descending intramedullary vessels to the trochanteric region and down into the femoral shaft. The emptying of intraosseous contrast material from the arthritic hip was delayed. 5. The phlebographs indicated that the abnormally high intraosseous pressure observed in osteoarthritis is caused by a high resistance to flow across the cortex of the proximal part of the femur. 6. The aching rest pain typical of severe osteoarthritis was noted only in patients with intraosseous femoral neck pressure above 40 millimetres of mercury, an indication that this type of pain is caused by intramedullary hypertension. The decrease of arteriovenous pressure difference, caused by increase of resistance to venous outflow, is probably accompanied by disturbances of nutritive flow. This "venous ischaemia" may play an important role for the structural changes of cancellous bone in osteoarthritis

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

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

The patellofemoral joint is an important source of symptoms in osteoarthritis of the knee. We have used a newly designed surgical model of patellar strengthening to induce osteoarthritis in BALB/c mice and to establish markers by investigating the relationship between osteoarthritis and synovial levels of matrix metalloproteinases (MMPs). Osteoarthritis was induced by using this microsurgical technique under direct vision without involving the cavity of the knee. Degeneration of cartilage was assessed by the Mankin score and synovial tissue was used to determine the mRNA expression levels of MMPs. Irrigation fluid from the knee was used to measure the concentrations of MMP-3 and MMP-9. Analysis of cartilage degeneration was correlated with the levels of expression of MMP. After operation the patellofemoral joint showed evidence of mild osteoarthritis at eight weeks and further degenerative changes by 12 weeks. The level of synovial MMP-9 mRNA correlated with the Mankin score at eight weeks, but not at 12 weeks. The levels of MMP-2, MMP-3 and MMP-14 mRNA correlated with the Mankin score at 12 weeks. An increase in MMP-3 was observed from four weeks up to 16 weeks. MMP-9 was notably increased at eight weeks, but the concentration at 16 weeks had decreased to the level observed at four weeks. Our observations suggest that MMP-2, MMP-3 and MMP-14 could be used as markers of the progression of osteoarthritic change

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

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

Objectives. Sagittal alignment of the lumbosacral spine, and specifically pelvic incidence (PI), has been implicated in the development of spine pathology, but generally ignored with regards to diseases of the hip. We aimed to determine if increased PI is correlated with higher rates of hip osteoarthritis (HOA). The effect of PI on the development of knee osteoarthritis (KOA) was used as a negative control. Methods. We studied 400 well-preserved cadaveric skeletons ranging from 50 to 79 years of age at death. Each specimen’s OA of the hip and knee were graded using a previously described method. PI was measured from standardised lateral photographs of reconstructed pelvises. Multiple regression analysis was performed to determine the relationship between age and PI with HOA and KOA. Results. The mean age was 60.2 years (standard deviation (. sd. ) 8.1), and the mean PI was 46.7° (. sd. 10.7°). Multiple regression analysis demonstrated a significant correlation between increased PI and HOA (standardised beta = 0.103, p = 0.017). There was no correlation between PI and KOA (standardised beta = 0.003, p = 0.912). Conclusion. Higher PI in the younger individual may contribute to the development of HOA in later life. Cite this article: Dr J. J. Gebhart. Relationship between pelvic incidence and osteoarthritis of the hip. Bone Joint Res 2016;5:66–72. DOI: 10.1302/2046-3758.52.2000552

This study validates the short-form WOMAC function scale for assessment of conservative treatment of osteoarthritis of the knee. Data were collected before treatment and six and nine months later, from 100 patients with osteoarthritis of the knee to determine the validity, internal consistency, test-retest reliability, floor and ceiling effects, and responsiveness of the short-form WOMAC function scale. The scale showed high correlation with the traditional WOMAC and other measures. The internal consistency was good (Cronbach α: 0.88 to 0.95) and an excellent test-retest reliability was found (Lin’s concordance correlation coefficient (ρ. c. ): 0.85 to 0.94). The responsiveness was adequate and comparable to that of the traditional WOMAC (standardised response mean 0.56 to 0.44 and effect size 0.64 to 0.57) and appeared not to be significantly affected by floor or ceiling effects (0% and 7%, respectively). The short-form WOMAC function scale is a valid, reliable and responsive alternative to the traditional WOMAC in the evaluation of patients with osteoarthritis of the knee managed conservatively. It is simple to use in daily practice and is therefore less of a burden for patients in clinical trials

Our aim in this prospective study was to evaluate the outcome of total shoulder replacement in the treatment of young and middle-aged active patients with primary glenohumeral osteoarthritis. We reviewed 21 patients (21 shoulders) with a mean age of 55 years (37 to 60). The mean follow-up was seven years (5 to 9). The same anatomical, third-generation, cemented implant had been used in all patients. All the patients were evaluated radiologically and clinically using the Constant and Murley score. No patients required revision. In one a tear of the supraspinatus tendon occurred. Overall, 20 patients (95%) were either very satisfied (n = 18) or satisfied (n = 2) with the outcome. Significant differences (p < 0.0001) were found for all categories of the Constant and Murley score pre- and post-operatively. The mean Constant and Murley score increased from 24.1 points (10 to 45) to 64.5 points (39 to 93), and the relative score from 30.4% (11% to 50%) to 83% (54% to 116%). No clinical or radiological signs of loosening of the implant were seen. For young and middle-aged patients with osteoarthritis, third-generation total shoulder replacement is a viable method of treatment with a low rate of complications and excellent results in the mid-term

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

In this retrospective study we have assessed the results of low tibial valgus osteotomy for varus-type osteoarthritis of the ankle and its indications. We performed an opening wedge osteotomy in 25 women (26 ankles). The mean follow-up was for eight years and three months (2 years 3 months to 17 years 11 months). Of the 26 ankles, 19 showed excellent or good clinical results. Their mean scores for pain, walking, and activities of daily living were significantly improved but there was no change in the range of movement. In the ankles which were classified radiologically as stage 2 according to our own grading system, with narrowing of the medial joint space, and in 11 as stage 3a, with obliteration of the joint space at the medial malleolus only, the joint space recovered. In contrast, such recovery was seen in only two of 12 ankles classified as stage 3b, with obliteration of the joint space advancing to the upper surface of the dome of the talus. Low tibial osteotomy is indicated for varus-type osteoarthritis of stage 2 or stage 3a

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

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

Medial tibial plateaux excised during 46 unicompartmental arthroplasties for osteoarthritis were collected and photographed. The anterior cruciate ligament was intact in all joints. In every case the cartilage and bone erosion was centred anteriorly on the plateau and the posterior cartilage was intact. The site of the lesion and the intact state of the cruciate ligaments taken together explain why varus deformity was observed only in the extended knee, and why the deformity was correctable and had not become fixed. Failure of the anterior cruciate ligament may allow the erosion to extend posteriorly, producing fixed varus deformity and leading to degeneration of the lateral compartment. Anteromedial osteoarthritis is a distinct clinicopathological entity; its radiographic features enable it to be diagnosed from lateral radiographs; its anatomical features render it suitable for treatment by unicompartmental arthroplasty

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

We investigated 60 patients (89 feet) with a mean age of 64 years (61 to 67) treated for congenital clubfoot deformity, using standardised weight-bearing radiographs of both feet and ankles together with a functional evaluation. Talocalcaneal and talonavicular relationships were measured and the degree of osteo-arthritic change in the ankle and talonavicular joints was assessed. The functional results were evaluated using a modified Laaveg-Ponseti score. The talocalcaneal (TC) angles in the clubfeet were significantly lower in both anteroposterior (AP) and lateral projections than in the unaffected feet (p < 0.001 for both views). There was significant medial subluxation of the navicular in the clubfeet compared with the unaffected feet (p < 0.001). Severe osteoarthritis in the ankle joint was seen in seven feet (8%) and in the talonavicular joint in 11 feet (12%). The functional result was excellent or good (≥ 80 points) in 29 patients (48%), and fair or poor (< 80 points) in 31 patients (52%). Patients who had undergone few (0 to 1) surgical procedures had better functional outcomes than those who had undergone two or more procedures (p < 0.001). There was a significant correlation between the functional result and the degree of medial subluxation of the navicular (p < 0.001, r. 2 . = 0.164), the talocalcaneal angle on AP projection (p < 0.02, r2 = 0.025) and extent of osteoarthritis in the ankle joint (p < 0.001). We conclude that poor functional outcome in patients with congenital clubfoot occurs more frequently in those with medial displacement of the navicular, osteoarthritis of the talonavicular and ankle joints, and a low talocalcaneal angle on the AP projection, and in patients who have undergone two or more surgical procedures. However, the ankle joint in these patients appeared relatively resistant to the development of osteoarthritis

Osteoarthritis, as seen in the hip, is a disease which eventually embraces all the tissues of the joint but begins as a reaction of the juxta-chondral blood vessels to a degeneration of the articular cartilage; this reaction results in a hyperaemia of the bone. To our surprise we found that daily use preserves rather than "wears out" articular cartilage; indeed inadequate use is the commonest cause of cartilage degeneration and ensuing vascular invasion. To this factor are added the effects of excessive pressure in the many patients who require surgical treatment for advanced osteoarthritis of a hip the seat of some anatomical incongruity. This etiology based on cartilage suffering does not exclude, but indeed explains, the osteoarthritis implanted on joints of a normal shape which have been previously affected by acute or chronic inflammation or by hormonal dysfunction, such as acromegalic osteoarthritis. The stimulus to vessel growth and invasion is the same in all these cases—namely cartilage damage. Once the vessels have entered the cartilage the bone and marrow of the osteophyte are inevitably laid down. What is so damaging in osteoarthritis seems to be not the degeneration of the cartilage but the vigorous and persistent attempt at repair, an attempt which aggravates the already disordered function of the joint not only by osteophyte formation but by the hypervascularity which weakens the structure of the bone beyond the point where it can carry its increased load. The collapse that follows provokes further reparative efforts with the same deplorable results. The osteoarthritic process thus appears to be an attempt to transform a decaying joint into a youthful one and for this, as in the miraculous rejuvenation depicted in Goethe's Faust, a high price must ultimately be paid

Using radiography and computer tomography (CT) we studied the morphology of 83 hips in 69 Caucasian adults with osteoarthritis secondary to developmental dysplasia of the hip (DDH). A previously published series of 310 hips with primary osteoarthritis was used as a control group. According to the Crowe classification, 33 of the dysplastic hips were graded as class I, 27 as class II and 23 as class III or class IV. The intramedullary femoral canal had reduced mediolateral and anteroposterior dimensions in all groups compared with the control group. Only in Crowe class II hips was the femoral neck-shaft angle increased. The proximal femur had more anteversion in all the developmental dysplasia of the hip groups, ranging from 2° to 80°. Templated measurement of acetabular dimensions for plain radiography closely matched measurements taken by CT. The results of our study confirm the observations previously confined to the Japanese population