Phenotype and energy metabolism differ between osteoarthritic chondrocytes from male compared to female patients: Implications for sexual dimorphism in osteoarthritis development?

OBJECTIVES: The prevalence and severity of knee osteoarthritis (OA) are greater in females than males. The purpose of this study was to determine whether there is an underlying difference in the biology of OA chondrocytes between males and females. METHODS: Chondrocytes were obtained following knee arthroplasty from male and female patients with primary OA. Phenotype marker expression, glucose and fat consumption, and rates of glycolysis and oxidative phosphorylation were compared between females and males. RNAi was used to determine the consequences of differential expression of Sry-box transcription factor 9 (SOX9) and PGC1α between males and females. RESULTS: OA chondrocytes from male donors showed elevated ribonucleic acid (RNA) and protein levels of SOX9, elevated COL2A1 protein synthesis, higher glucose consumption, and higher usage of glycolysis compared to females. OA chondrocytes from females had higher PGC1α protein levels, higher fat consumption, and higher oxidative energy metabolism than males. Knockdown of SOX9 reduced expression of COL2A1 to a greater extent in male OA chondrocytes than females whereas knockdown of PGC1α reduced COL2A1 expression in females but not males. Expression of ACAN and the glycolytic enzyme PGK1 was also reduced in males but not females following SOX9 knockdown. CONCLUSIONS: OA chondrocyte phenotype and energy metabolism differ between males and females. Our results indicate transcriptional control of COL2A1 differs between the two. Differences in chondrocyte biology between males and females imply the underlying mechanisms involved in OA may also differ, highlighting the need to consider sex and gender when investigating pathogenesis and potential treatments for OA.

Concentration-dependent effects of leptin on osteoarthritis-associated changes in phenotype of human chondrocytes.

Metabolic syndrome is a risk factor for osteoarthritis. Elevated leptin levels have been implicated as a potential cause of this association. Previous studies have shown that supra-physiological leptin concentrations can induce osteoarthritis-like changes in chondrocyte phenotype. Here, we tested the effects of leptin in the concentration range found in synovial fluid on chondrocyte phenotype. Chondrocytes isolated from macroscopically normal regions of cartilage within osteoarthritic joints from patients undergoing knee arthroplasty, all with body mass index >30 kg/m2 were treated with 2-40 ng/ml leptin for 24 h. Chondrocyte phenotype marker expression was measured by RT-qPCR and western blot. The role of HES1 in mediating the effects of leptin was determined by gene knockdown using RNAi and over-expression using adenoviral-mediated gene delivery. Treatment of chondrocytes with 20 or 40 ng/ml leptin resulted in decreased SOX9 levels and decreased levels of the SOX9-target genes COL2A1 and ACAN. Levels of HES1 were lower and ADAMTS5 higher in chondrocytes treated with 20 or 40 ng/ml leptin. HES1 knockdown resulted in increased ADAMTS5 expression whereas over-expression of HES1 prevented the leptin-induced increase in ADAMTS5. An increase in MMP13 expression was only evident in chondrocytes treated with 40 ng/ml leptin and was not mediated by HES1 activity. High concentrations of leptin can cause changes in chondrocyte phenotype consistent with those seen in osteoarthritis. Synovial fluid leptin concentrations of this level are typically observed in patients with metabolic syndrome and/or women, suggesting elevated leptin levels may form part of the multifactorial network that leads to osteoarthritis development in these patients.

Better post-operative outcomes at 1-year follow-up are associated with lower levels of pre-operative synovitis and higher levels of IL-6 and VEGFA in unicompartmental knee arthroplasty patients.

PURPOSE: Osteoarthritis (OA) is associated with inflammation, and residual inflammation may influence outcomes following knee arthroplasty. This may be more relevant for patients undergoing unicompartmental knee arthroplasty (UKA) due to larger remaining areas of native tissue. This study aimed to: (1) characterise inflammatory profiles for medial UKA patients and (2) investigate whether inflammation markers are associated with post-operative outcomes. METHODS: This prospective, observational study has national ethics approval. Bloods, synovial fluid, tibial plateaus and synovium were collected from medial UKA patients in between 1 January 2021 and 31 December 2021. Cytokine and chemokine concentrations in serum and synovial fluid (SF) were measured with multiplexed assays. Disease severity of cartilage and synovium was assessed using validated histological scores. Post-operative outcomes were measured with Oxford Knee Score (OKS), Forgotten Joint Score (FJS-12) and pain scores. RESULTS: The study included 35 patients. SF VEGFA was negatively correlated with pre-operative pain at rest (r - 0.5, p = 0.007), and FJS-12 at six-week (r 0.44, p = 0.02), six-month (r 0.61, p < 0.01) and one-year follow-up (r 0.63, p = 0.03). Serum and SF IL-6 were positively correlated with OKS at early follow-up (serum 6 weeks, r 0.39, p = 0.03; 6 months, r 0.48, p < 0.01; SF 6 weeks, r 0.35, p = 0.04). At six weeks, increased synovitis was negatively correlated with improvements in pain at rest (r - 0.41, p = 0.03) and with mobilisation (r - 0.37, p = 0.047). CONCLUSION: Lower levels of synovitis and higher levels of IL-6 and VEGFA were associated with better post-operative outcomes after UKA, which could be helpful for identifying UKA patients in clinical practice. LEVEL OF EVIDENCE: Level IV case series.

Ethnicity, sex, and socioeconomic disparities in the treatment of traumatic rotator cuff injuries in Aotearoa/New Zealand.

HYPOTHESIS AND BACKGROUND: Traumatic rotator cuff injuries can be a leading cause of prolonged shoulder pain and disability and contribute to significant morbidity and health care costs. Previous studies have shown evidence of sociodemographic disparities with these injuries. The purpose of this nationwide study was to better understand these disparities based on ethnicity, sex, and socioeconomic status, in order to inform future health care strategies. METHODS: Accident Compensation Corporation (ACC) is a no-fault comprehensive compensation scheme encompassing all of Aotearoa/New Zealand (population in 2018, 4.7 million). Using the ACC database, traumatic rotator cuff injuries were identified between January 2010 and December 2018. Injuries were categorized by sex, ethnicity, age, and socioeconomic deprivation index of the claimant. RESULTS: During the 9-year study period, there were 351,554 claims accepted for traumatic rotator cuff injury, which totaled more than NZ$960 million. The greatest proportion of costs was spent on vocational support (49.8%), then surgery (26.3%), rehabilitation (13.1%), radiology (8.1%), general practitioner (1.6%), and "Other" (1.1%). Asian, Maori (indigenous New Zealanders), and Pacific peoples were under-represented in the age-standardized proportion of total claims and had lower rates of surgery than Europeans. Maori had higher proportion of costs spent on vocational support and lower proportions spent on radiology, rehabilitation, and surgery than Europeans. Males had higher number and costs of claims and were more likely to have surgery than females. There were considerably fewer claims from areas of high socioeconomic deprivation. DISCUSSION AND CONCLUSION: This large nationwide study demonstrates the important and growing economic burden of rotator cuff injuries. Indirect costs, such as vocational supports, are a major contributor to the cost, suggesting improving treatment and rehabilitation protocols would have the greatest economic impact. This study has also identified sociodemographic disparities that need to be addressed in order to achieve equity in health outcomes.

The Strongest Oxford Knee Score Predictors of Subsequent Revision are "Overall Pain," "Limping When Walking," and "Knee Giving Way".

BACKGROUND: The Oxford Knee Score (OKS) is used to measure knee arthroplasty outcomes; however, it is unclear which questions are more relevant. Our aims were to (1) identify which OKS question(s) were the strongest predictors of subsequent revision and (2) compare the predictive ability of the "pain" and "function" domains. METHODS: All primary total knee arthroplasties (TKAs) and unicompartmental knee arthroplasties (UKAs) in the New Zealand Joint Registry between 1999 and 2019 with an OKS at 6 months (TKA n = 27,708; UKA n = 8,415), 5 years (TKA n = 11,519; UKA n = 3,365) or 10 years (TKA n = 6,311; UKA n = 1,744) were included. Prediction models were assessed using logistic regressions and receiver operating characteristic analyses. RESULTS: A reduced model with 3 questions ("overall pain," "limping when walking," "knee giving way") showed better diagnostic ability than full OKS for predicting UKA revision at 6 months (area under the curve [AUC]: 0.80 versus 0.78; P < .01) and 5 years (0.81 versus 0.77; P = .02), and comparable diagnostic ability for predicting TKA revision at all time points (6 months, 0.77 versus 0.76; 5 years, 0.78 versus 0.75; 10 years, 0.76 versus 0.73; all not significant), and UKA revision at 10 years (0.80 versus 0.77; not significant). The pain domain had better diagnostic ability for predicting subsequent revision for both procedures at 5 and 10 years. CONCLUSION: Questions on "overall pain", "limping when walking", and "knee giving way" were the strongest predictors of subsequent revision. Attention to low scores from these questions during follow-up may allow for prompt identification of patients most at risk of revision.

What are the perceived benefits and barriers to the use of robot-assisted total knee arthroplasty? A survey of members of the European Knee Society.

PURPOSE: Members of the European Knee Society (EKS) recently took part in an online questionnaire on robot-assisted TKA. The purpose of this study was to report and analyse the questionnaire results on the demographics of users versus non-users, the drivers for users of the technology, and the barriers or limitations that hinder the uptake of robot-assisted TKA. METHODS: The questionnaire was composed of 16 questions covering surgeon demographics and drivers for or barriers to the use of robotics. Responses on four- or five-point Likert scales were trichotomised depending on the type of question ("not important" - "moderately important" - "important/very important" or "fully disagree/disagree" - "neutral" - "agree/fully agree"). Consensus on a statement was defined as at least 75% agreement. RESULTS: There was a 67% response rate. Forty-five surgeons performed conventional TKA, of which 78% aimed for systematic alignment, while 22 performed robot-assisted TKA, of which 82% aimed for individualised alignment, and 16 performed technology-assisted TKA, of which 56% aimed for systematic alignment. Respondents agreed that robotics significantly impact accuracy of bone cuts (51/62, 82%), intra-operative feedback on ligament balancing (56/62, 90%) as well as bone cut orientation and implant positioning (57/ 62, 92%), and assistance to customise alignment (56/62, 90%). Respondents agreed that associated costs (14/18, 78%) are an important aspect for not using or to stop using robotics. CONCLUSION: The majority of respondents still perform conventional TKA (54%), while only a small portion perform robot-assisted TKA (27%) or other technology-assisted TKA (19%). Most robot users aim for individualised lower limb alignment, whereas most other surgeons aimed for systematic lower limb alignment. There is consensus that robotic assistance has a positive impact on accuracy of bone cuts and alignment, but no consensus on its impact on other peri- or post-operative outcomes. Finally, the associated cost of robot-assisted TKA remains the main barrier to its uptake. LEVEL OF EVIDENCE: V.

Differential Effects of Hypoxia versus Hyperoxia or Physoxia on Phenotype and Energy Metabolism in Human Chondrocytes from Osteoarthritic Compared to Macroscopically Normal Cartilage.

Chondrocyte phenotype and energy metabolism are altered in osteoarthritis (OA). However, most studies characterising the change in human chondrocyte behaviour in OA have been conducted in supraphysiological oxygen concentrations. The purpose of this study was to compare phenotype and energy metabolism in chondrocytes from macroscopically normal (MN) and OA cartilage maintained in 18.9% (standard tissue culture), 6% (equivalent to superficial zone of cartilage in vivo) or 1% oxygen (equivalent to deep zone of cartilage in vivo). MMP13 production was higher in chondrocytes from OA compared to MN cartilage in hyperoxia and physoxia but not hypoxia. Hypoxia promoted SOX9, COL2A1 and ACAN protein expression in chondrocytes from MN but not OA cartilage. OA chondrocytes used higher levels of glycolysis regardless of oxygen availability. These results show that differences in phenotype and energy metabolism between chondrocytes from OA and MN cartilage differ depending on oxygen availability. OA chondrocytes show elevated synthesis of cartilage-catabolising enzymes and chondrocytes from MN cartilage show reduced cartilage anabolism in oxygenated conditions. This is relevant as a recent study has shown that oxygen levels are elevated in OA cartilage in vivo. Our findings may indicate that this elevated cartilage oxygenation may promote cartilage loss in OA.

Clinical outcomes following open anterior shoulder stabilization for glenohumeral instability in the young collision athlete.

BACKGROUND: Anterior glenohumeral instability occurs most commonly in those aged 15-29, with 72% of individuals younger than 22 years suffering recurrent episodes; collision athletes are at particular risk. In the setting of subcritical glenoid bone loss, arthroscopic Bankart repair is widely used despite concerns of recurrent dislocations when compared with open techniques. Furthermore, indications for bone-block procedures are evolving with the Latarjet procedure being favored amongst recent authors as a primary stabilization method in elite and contact athletes. OBJECTIVE: To determine the efficacy of open modified Bankart stabilization in treating anterior glenohumeral instability in young collision athletes. METHODS: This was a retrospective review of outcomes of consecutive patients aged 15-20 years who underwent unilateral or bilateral open stabilization for recurrent anterior glenohumeral instability over a 7-year period (2007-2015). The cohort was selected as recent literature suggests that this is the group with the highest redislocation rate and poorest outcomes. Outcome assessments included redislocation rate, return to sport, pain score, patient-related satisfaction scores, and the Western Ontario Shoulder Instability Index. RESULTS: A total of 60 patients (55 male: 5 female) of mean age 18 years (range: 15-20 years) were available for follow-up at 7 years. All but 3 were competitive athletes with 18 competing regionally and 9 internationally; rugby union and rugby league represent the most common sports. Fifty-five of 60 (92%) have returned to their desired level of sport with 62% of athletes returning to their previous level of competition sport and 1 retuning at a higher level. The mean postoperative pain score was 2.5/10. The mean time to return to play was 14 months (range: 5-48 months). Eight of 60 shoulders reported redislocation (13%), 7 of these being traumatic dislocations after return to high-impact sporting activities. At 7 years of follow-up, 4 of 60 shoulders (7%) had undergone revision surgery. CONCLUSION: Young collision athletes represent a challenging cohort of instability patients. This study of open modified Bankart in young collision sport athletes revealed excellent outcomes with 92% return to sport and a low revision rate. The results from this cohort rival those of arthroscopic repair. The open procedure described here in this 7-year series represents a robust, reliable technique that could be considered as an alternative to arthroscopic Bankart due to concern for recurrence, while avoiding potential morbidity and complication of bone-block procedures. There is still a role for the open modified Bankart procedure in treating traumatic anterior instability.

A high-fat diet has negative effects on tendon resident cells in an in vivo rat model.

BACKGROUND: Tendinopathy is a major complication of diet-induced obesity. However, the effects of a high-fat diet (HFD) on tendon have not been well characterised. We aimed to determine: [1] the impact of a HFD on tendon properties and gene expression; and [2] whether dietary transition to a control diet (CD) could restore normal tendon health. METHODS: Sprague-Dawley rats were randomised into three groups from weaning and fed either a: CD, HFD or HFD for 12 weeks and then CD thereafter (HF-CD). Biomechanical, histological and structural evaluation of the Achilles tendon was performed at 17 and 27 weeks of age. Tail tenocytes were isolated with growth rate and collagen production determined. Tenocytes and activated THP-1 cells were exposed to conditioned media (CM) of visceral adipose tissue explants, and gene expression was analysed. RESULTS: There were no differences in the biomechanical, histological or structural tendon properties between groups. However, tenocyte growth and collagen production were increased in the HFD group at 27 weeks. There was lower SOX-9 expression in the HFD and HF-CD groups at 17 weeks and higher expression of collagen-Iα1 and matrix metalloproteinase-13 in the HFD group at 27 weeks. THP-1 cells exposed to adipose tissue CM from animals fed a HFD or HF-CD had lower expression of Il-10 and higher expression of Il-1ß. CONCLUSIONS: In this rodent model, a HFD negatively altered tendon cell characteristics. Dietary intervention restored some gene expression changes; however, adipose tissue secretions from the HF-CD group promoted an increased inflammatory state in macrophages. These changes may predispose tendon to injury and adverse events later in life.

Revision indications for medial unicompartmental knee arthroplasty: a systematic review.

INTRODUCTION: Unicompartmental knee arthroplasty (UKA) has advantages over total knee arthroplasty including fewer complications and faster recovery; however, UKAs also have higher revision rates. Understanding reasons for UKA failure may, therefore, allow for optimized clinical outcomes. We aimed to identify failure modes for medial UKAs, and to examine differences by implant bearing, cement use and time. MATERIALS AND METHODS: A systematic review was conducted by searching MedLine, EMBASE, CINAHL and Cochrane databases from 2000 to 2020. Studies were selected if they included ≥ 250 participants, ≥ 10 failures and reported all failure modes of medial UKA performed for osteoarthritis (OA). RESULTS: A total of 24 cohort and 2 registry-based studies (levels II and III) were selected. The most common failure modes were aseptic loosening (24%) and OA progression (30%). Earliest failures (< 6 months) were due to infection (40%), bearing dislocation (20%), and fracture (20%); mid-term failures (> 2 years to 5 years) were due to OA progression (33%), aseptic loosening (17%) and pain (21%); and late-term (> 10 years) failures were mostly due to OA progression (56%). Rates of failure from wear were higher with fixed-bearing prostheses (5% cf. 0.3%), whereas rates of bearing dislocations were higher with mobile-bearing prostheses (14% cf. 0%). With cemented components, there was a high rate of failure due to aseptic loosening (27%), which was reduced with uncemented components (4%). CONCLUSIONS: UKA failure modes differ depending on implant design, cement use and time from surgery. There should be careful consideration of implant options and patient selection for UKA.

Varus alignment of the proximal tibia is associated with structural progression in early to moderate varus osteoarthritis of the knee.

PURPOSE: Lower limb malalignment is a strong predictor of progression in knee osteoarthritis. The purpose of this study is to identify the individual alignment variables that predict progression in early to moderate osteoarthritis of the knee. METHOD: A longitudinal cohort study using data from the Osteoarthritis Initiative. In total, 955 individuals (1329 knees) with early to moderate osteoarthritis (Kellgren-Lawrence grade 1, 2 or 3) were identified. All subjects had full-limb radiographs analysed using the Osteotomy module within Medicad® Classic (Hectec GMBH) to give a series of individual alignment variables relevant to the coronal alignment of the lower limb. Logistic regression models, with generalised estimating equations were used to identify which of these individual alignment variables predict symptom worsening (WOMAC score > 9 points) and or structural progression (joint space narrowing progression in the medial compartment > 0.7mm) over 24 months. RESULTS: Individual alignment variable were associated with both valgus and varus alignment (mechanical Lateral Distal Femoral Angle, Medial Proximal Tibial Angle and mechanical Lateral Distal Tibial Angle). Only the Medial Proximal Tibial Angle was significantly associated with structural progression and none of the variables was associated with symptom progression. The odds of joint space narrowing progression in the medial compartment occurring at 24 months increased by 21% for every one degree decrease (more varus) in Medial Proximal Tibial Angle (p < 0.001) CONCLUSIONS: Our results suggest that the risk of structural progression in the medial compartment is associated with greater varus alignment of the proximal tibia. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Surgical interventions for symptomatic mild to moderate knee osteoarthritis.

BACKGROUND: Osteoarthritis affecting the knee is common and represents a continuum of disease from early cartilage thinning to full-thickness cartilage loss, bony erosion, and deformity. Many studies do not stratify their results based on the severity of the disease at baseline or recruitment. OBJECTIVES: To assess the benefits and harms of surgical intervention for the management of symptomatic mild to moderate knee osteoarthritis defined as knee pain and radiographic evidence of non-end stage osteoarthritis (Kellgren-Lawrence grade 1, 2, 3 or equivalent on MRI/arthroscopy). Outcomes of interest included pain, function, radiographic progression, quality of life, short-term serious adverse events, re-operation rates and withdrawals due to adverse events. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase up to May 2018. We also conducted searches of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform for ongoing trials. Authors of trials were contacted if some but not all their participants appeared to fit our inclusion criteria. SELECTION CRITERIA: We included randomised controlled trials that compared surgery to non-surgical interventions (including sham and placebo control groups, exercise or physiotherapy, and analgesic or other medication), injectable therapies, and trials that compared one type of surgical intervention to another surgical intervention in people with symptomatic mild to moderate knee osteoarthritis. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials and extracted data using standardised forms. We analysed the quality of evidence using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. MAIN RESULTS: A total of five studies involving 566 participants were identified as eligible for this review. Single studies compared arthroscopic partial meniscectomy to physical therapy (320 participants), arthroscopic surgery (debridement ± synovectomy ± chondroplasty) to closed needle joint lavage with saline (32 participants) and high tibial osteotomy surgery to knee joint distraction surgery (62 participants). Two studies (152 participants) compared arthroscopic surgery (washout ± debridement; debridement) to a hyaluronic acid injection. Only one study was at low risk of selection bias, and due to the difficulty of blinding participants to their treatment, all studies were at risk of performance and detection bias.Reporting of results in this summary has been restricted to the primary comparison: surgical intervention versus non-surgical intervention.A single study, included 320 participants with symptoms consistent with meniscal tear. All subjects had the meniscal tear confirmed on knee MRI and radiographic evidence of mild to moderate osteoarthritis (osteophytes, cartilage defect or joint space narrowing). Patients with severe osteoarthritis (KL grade 4) were excluded. The study compared arthroscopic partial meniscectomy and physical therapy to physical therapy alone (a six-week individualised progressive home exercise program). This study was at low risk of selection bias and outcome reporting biases, but was susceptible to performance and detection biases. A high rate of cross-over (30.2%) occurred from the physical therapy group to the arthroscopic group.Low-quality evidence suggests there may be little difference in pain and function at 12 months follow-up in people who have arthroscopic partial meniscectomy and those who have physical therapy. Evidence was downgraded to low quality due to risk of bias and imprecision.Mean pain was 19.3 points on a 0 to 100 point KOOS pain scale with physical therapy at 12 months follow-up and was 0.2 points better with surgery (95% confidence interval (CI) 4.05 better to 3.65 points worse with surgery, an absolute improvement of 0.2% (95% CI 4% better to 4% worse) and relative improvement 0.4% (95% CI 9% better to 8% worse) (low quality evidence). Mean function was 14.5 on a 0 to 100 point KOOS function scale with physical therapy at 12 months follow-up and 0.8 points better with surgery (95% CI 4.3 better to 2.7 worse); 0.8% absolute improvement (95% CI 4% better to 3% worse) and 2.1% relative improvement (95% CI 11% better to 7% worse) (low quality evidence).Radiographic structural osteoarthritis progression and quality of life outcomes were not reported.Due to very low quality evidence, we are uncertain if surgery is associated with an increased risk of serious adverse events, incidence of total knee replacement or withdrawal rates. Evidence was downgraded twice due to very low event rates, and once for risk of bias.At 12 months, the surgery group had a total of three serious adverse events including fatal pulmonary embolism, myocardial infarction and hypoxaemia. The physical therapy alone group had two serious adverse events including sudden death and stroke (Peto OR 1.58, 95% CI 0.27 to 9.21); 1% more events with surgery (95% CI 2% less to 3% more) and 58% relative change (95% CI 73% less to 821% more). One participant in each group withdrew due to adverse events.Two of 164 participants (1.2%) in the physical therapy group and three of 156 in the surgery group underwent conversion to total knee replacement within 12 months (Peto OR 1.76, 95% CI 0.43 to 7.13); 1% more events with surgery (95% CI 2% less to 5% more); 76% relative change (95% CI 57% less to 613% more). AUTHORS' CONCLUSIONS: The review found no placebo-or sham-controlled trials of surgery in participants with symptomatic mild to moderate knee osteoarthritis. There was low quality evidence that there may be no evidence of a difference between arthroscopic partial meniscectomy surgery and a home exercise program for the treatment of this condition. Similarly, low-quality evidence from a few small trials indicates there may not be any benefit of arthroscopic surgery over other non-surgical treatments including saline irrigation and hyaluronic acid injection, or one type of surgery over another. We are uncertain of the risk of adverse events or of progressing to total knee replacement due to very small event rates. Thus, there is uncertainty around the current evidence to support or oppose the use of surgery in mild to moderate knee osteoarthritis. As no benefit has been demonstrated from the low quality trials included in this review, it is possible that future higher quality trials for these surgical interventions may not contradict these results.

The effect of patient age at intervention on risk of implant revision after total replacement of the hip or knee: a population-based cohort study.

BACKGROUND: Total joint replacements for end-stage osteoarthritis of the hip and knee are cost-effective and demonstrate significant clinical improvement. However, robust population based lifetime-risk data for implant revision are not available to aid patient decision making, which is a particular problem in young patient groups deciding on best-timing for surgery. METHODS: We did implant survival analysis on all patients within the Clinical Practice Research Datalink who had undergone total hip replacement or total knee replacement. These data were adjusted for all-cause mortality with data from the Office for National Statistics and used to generate lifetime risks of revision surgery based on increasing age at the time of primary surgery. FINDINGS: We identified 63 158 patients who had undergone total hip replacement and 54 276 who had total knee replacement between Jan 1, 1991, and Aug 10, 2011, and followed up these patients to a maximum of 20 years. For total hip replacement, 10-year implant survival rate was 95·6% (95% CI 95·3-95·9) and 20-year rate was 85·0% (83·2-86·6). For total knee replacement, 10-year implant survival rate was 96·1% (95·8-96·4), and 20-year implant survival rate was 89·7% (87·5-91·5). The lifetime risk of requiring revision surgery in patients who had total hip replacement or total knee replacement over the age of 70 years was about 5% with no difference between sexes. For those who had surgery younger than 70 years, however, the lifetime risk of revision increased for younger patients, up to 35% (95% CI 30·9-39·1) for men in their early 50s, with large differences seen between male and female patients (15% lower for women in same age group). The median time to revision for patients who had surgery younger than age 60 was 4·4 years. INTERPRETATION: Our study used novel methodology to investigate and offer new insight into the importance of young age and risk of revision after total hip or knee replacement. Our evidence challenges the increasing trend for more total hip replacements and total knee replacements to be done in the younger patient group, and these data should be offered to patients as part of the shared decision making process. FUNDING: Oxford Musculoskeletal Biomedical Research Unit, National Institute for Health Research.

Surgical versus conservative interventions for treating anterior cruciate ligament injuries.

BACKGROUND: Rupture of the anterior cruciate ligament (ACL) is a common injury, mainly affecting young, physically active individuals. The injury is characterised by joint instability, leading to decreased activity, which can lead to poor knee-related quality of life. It is also associated with increased risk of secondary osteoarthritis of the knee. It is unclear whether stabilising the knee surgically via ACL reconstruction produces a better overall outcome than non-surgical (conservative) treatment. OBJECTIVES: To assess the effects of surgical versus conservative interventions for treating ACL injuries. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (18 January 2016), the Cochrane Central Register of Controlled Trials (2016, Issue 1), MEDLINE (1946 to January Week 1 2016), MEDLINE In-Process & Other Non-Indexed Citations (18 January 2016), EMBASE (1974 to 15 January 2016), trial registers (February 2016) and reference lists. SELECTION CRITERIA: We included randomised controlled trials that compared the use of surgical and conservative interventions in participants with an ACL rupture. We included any trial that evaluated surgery for ACL reconstruction using any method of reconstruction, type of reconstruction technique, graft fixation or type of graft. DATA COLLECTION AND ANALYSIS: Three review authors independently screened all titles and abstracts for potentially eligible studies, for which we then obtained full-text reports. Two authors then independently confirmed eligibility, extracted data and assessed the risk of bias using the Cochrane 'Risk of bias' tool. We used the GRADE approach to assess the overall quality of the evidence. MAIN RESULTS: We identified one study in which 141 young, active adults with acute ACL injury were randomised to either ACL reconstruction followed by structured rehabilitation (results reported for 62 participants) or conservative treatment comprising structured rehabilitation alone (results reported for 59 participants). Built into the study design was a formal option for subsequent (delayed) ACL reconstruction in the conservative treatment group, if the participant requested surgery and met pre-specified criteria.This study was deemed at low risk of selection and reporting biases, at high risk of performance and detection biases because of the lack of blinding and at unclear risk of attrition bias because of an imbalance in the post-randomisation exclusions. According to GRADE methodology, the overall quality of the evidence was low across different outcomes.This study identified no difference in subjective knee score (measured using the average score on four of the five sub-scales of the KOOS score (range from 0 (extreme symptoms) to 100 (no symptoms)) between ACL reconstruction and conservative treatment at two years (difference in KOOS-4 change from baseline scores: MD -0.20, 95% confidence interval (CI) -6.78 to 6.38; N = 121 participants; low-quality evidence), or at five years (difference in KOOS-4 final scores: MD -2.0, 95% CI -8.27 to 4.27; N = 120 participants; low-quality evidence). The total number of participants incurring one or more complications in each group was not reported; serious events reported in the surgery group were predominantly surgery-related, while those in conservative treatment group were predominantly knee instability. There were also incomplete data for total participants with treatment failure, including subsequent surgery. In the surgical group at two years, there was low-quality evidence of far fewer ACL-related treatment failures, when defined as either graft rupture or subsequent ACL reconstruction. This result is dominated by the uptake by 39% (23/59) of the participants in the conservative treatment group of ACL reconstruction for knee instability at two years and by 51% (30/59) of the participants at five years. There was low-quality evidence of little difference between the two groups in participants who had undergone meniscal surgery at anytime up to five years. There was low-quality evidence of no clinically important between-group differences in SF-36 physical component scores at two years. There was low-quality evidence of a higher return to the same or greater level of sport activity at two years in the ACL reconstruction group, but the wide 95% CI also included the potential for a higher return in the conservative treatment group. Based on an illustrative return to sport activities of 382 per 1000 conservatively treated patients, this amounts to an extra 84 returns per 1000 ACL-reconstruction patients (95% CI 84 fewer to 348 more). There was very low-quality evidence of a higher incidence of radiographically-detected osteoarthritis in the surgery group (19/58 (35%) versus 10/55 (18%)). AUTHORS' CONCLUSIONS: For adults with acute ACL injuries, we found low-quality evidence that there was no difference between surgical management (ACL reconstruction followed by structured rehabilitation) and conservative treatment (structured rehabilitation only) in patient-reported outcomes of knee function at two and five years after injury. However, these findings need to be viewed in the context that many participants with an ACL rupture remained symptomatic following rehabilitation and later opted for ACL reconstruction surgery. Further research, including the two identified ongoing trials, will help to address the limitations in the current evidence, which is from one small trial in a young, active, adult population.

Evidence in managing traumatic anterior shoulder instability: a scoping review.

BACKGROUND: Traumatic anterior shoulder instability (TASI) accounts for 95% of glenohumeral dislocations and is associated with soft tissue and bony pathoanatomies. Non-operative treatments include slings, bracing and physiotherapy. Operative treatment is common, including bony and soft-tissue reconstructions performed through open or arthroscopic approaches. There is management variation in patient pathways for TASI including when to refer and when to operate. METHODS: A scoping review of systematic reviews, randomised controlled trials, comparing operative with non-operative treatments and different operative treatments were the methods followed. Search was conducted for online bibliographic databases and reference lists of relevant articles from 2002 to 2012. Systematic reviews were appraised using AMSTAR (assessment of multiple systematic reviews) criteria. Controlled trials were appraised using the CONSORT (consolidation of standards of reporting trials) tool. RESULTS: Analysis of the reviews did not offer strong evidence for a best treatment option for TASI. No studies directly compare open, arthroscopic and structured rehabilitation programmes. Evaluation of arthroscopic studies and comparison to open procedures was difficult, as many of the arthroscopic techniques included are no longer used. Recurrence rate was generally considered the best measure of operative success, but was poorly documented throughout all studies. There was conflicting evidence on the optimal timing of intervention and no consensus on any scoring system or outcome measure. CONCLUSIONS: There is no agreement about which validated outcome tool should be used for assessing shoulder instability in patients. There is limited evidence regarding the comparative effectiveness of surgical and non-surgical treatment of TASI, including a lack of evidence regarding the optimal timing of such treatments. There is a need for a well-structured randomised control trial to assess the efficacy of surgical and non-surgical interventions for this common type of shoulder instability.

Robotic Assessment of Patella Tracking in Total Knee Arthroplasty.

OBJECTIVES: Robotic-tools have been developed to improve planning, accuracy and outcomes in total knee arthroplasty (TKA). The purpose of this study was to describe and illustrate a novel technique for assessing the patellofemoral (PFJ) in TKA using an imageless robotic platform. METHODS: A consecutive series of 30 R-TKA were undertaken by a single-surgeon utilising the described technique. A technique to dynamically assess the PFJ intra-operatively, pre and post implantation was developed. A full set of data from 9 cases was then collected and reviewed for analysis. A series of dynamic PFJ tracks collected intra-operatively pre and post implantation are presented. Furthermore, a full assessment of PFJ over and under-stuffing through a 90° arc of flexion is illustrated. Finally, a pre and post centre of rotation for the PFJ was defined and measured. RESULTS: The described technique was defined over a series of 30 R-TKA using the described robotic platform. Nine cases were analysed to determine what data could be measured using the robotic platform. Intra-operative real-time data allowed a visual assessment of PFJ tracking through a range of motion of 0° to 90° flexion pre and post-implantation. PFJ over and under-stuffing was also assessed intra-operatively through a range of motion of 0° to 90° flexion. Post operative analysis allowed a more detailed study to be performed, including defining a pre and post implantation centre of rotation (COR) for the patella. Defining the COR allowed the definition of a patella plane. Furthermore, patella mediolateral shift in full extension, and end flexion could be measured. CONCLUSION: Intra-operative assessment of the PFJ in TKA is challenging. Robotic tools have been developed to improve measurement, accuracy of delivery and outcomes in TKA. These tools can be adapted in novel ways to assess the PFJ, which may lead to further refinements in TKA techniques.

Accuracy and completeness of registry-reported unicompartmental knee arthroplasty revision.

INTRODUCTION: The key outcome of joint registries is revision events, which inform clinical practice and identify poor-performing implants. Registries record revision events and reasons, but accuracy may be limited by a lack of standardized definitions of revision. Our study aims to assess the accuracy and completeness of unicompartmental knee arthroplasty (UKA) revision and indications reported to the New Zealand Joint Registry (NZJR) with independent clinical review. METHODS: Case record review of 2272 patients undergoing primary UKA at four large tertiary hospitals between 2000 and 2017 was performed, identifying 158 patients who underwent revision. Detailed review of clinical findings, radiographs and operative data was performed to identify revision cases and the reasons for revision using a standardized protocol. These were compared to NZJR data using chi-squared and Fisher exact tests. RESULTS: The NZJR recorded 150 (95%) of all UKA revisions. Osteoarthritis progression was the most common reason on the systematic clinical review (35%), however, this was underreported to the registry (8%, P < 0.001). A larger proportion of revisions reported to the registry were for 'pain' (30% of cases vs. 5% on clinical review, P < 0.001). A reason for revision was not reported to the registry for 10% of cases. CONCLUSION: The NZJR had good capture of UKA revisions, but had significant differences in registry-reported revision reasons compared to our independent systematic clinical review. These included over-reporting of 'pain', under-reporting of osteoarthritis progression, and failing to identify a revision reason. Efforts to improve registry capture of revision reasons for UKA could be addressed through more standardized definitions of revision and tailored revision options for UKA on registry forms.

Associations of the Oxford Knee Score and knee arthroplasty revision at long-term follow-up.

BACKGROUND: Self-reported outcome measures are increasingly being collected for healthcare evaluation therefore it is prudent to understand their associations with patient outcomes. Our aims were to investigate: (1) if Oxford Knee Score (OKS) is associated with impending revision at long-term (5 and 10 years) follow-up, and (2) if decreased OKS at subsequent follow-ups is associated with higher risk of revision. PATIENTS AND METHODS: All total knee (TKAs) and unicompartmental knee arthroplasties (UKAs) between 1999 and 2019 in the New Zealand Joint Registry with an OKS at 6 months (TKA n = 27 708, UKA n = 8415), 5 years (TKA n = 11 519, UKA n = 3365) or 10 years (TKA n = 6311, UKA n = 1744) were included. Logistic regression determined associations of the OKS with revision within 2 years of each score. Change in OKS between timepoints were compared with revision risk. RESULTS: For every one-unit increase in OKS, the odds of TKA and UKA revision decreased by 10% and 11% at 6 months, 10% and 12% at 5 years and 9% and 5% at 10 years. For both procedures a decrease of seven or more OKS points from previous follow-up was associated with higher risk of revision (5 years: TKA 4.7% versus 0.5%, UKA 8.7% versus 0.9%; 10 years: TKA 4.4% versus 0.7%, UKA 11.3% versus 1.5%; all P < 0.01). CONCLUSION: The OKS had a strong negative association with risk of impending TKA and UKA revision from early to long-term (10+ years) follow-up. A decrease of seven or more points when compared with the previous follow-up was also associated with higher revision risk.

Similar Survivorship but Different Revision Reasons for Uncemented Mobile-Bearing and Cemented Fixed-Bearing Medial UKA: A Long-Term Population-Based Cohort Study of 2,015 Patients.

BACKGROUND: Long-term survivorship and accurate characterization of revision reasons in unicompartmental knee arthroplasty (UKA) are limited by a lack of long-term data and standardized definitions of revision. The aim of this study was to identify survivorship, risk factors, and reasons for revision in a large cohort of medial UKAs with long-term follow-up (up to 20 years). METHODS: Patient, implant, and revision details for 2,015 primary medial UKAs (mean follow-up, 8 years) were recorded following systematic clinical and radiographic review. Survivorship and risk of revision were analyzed using Cox proportional hazards. Reasons for revision were analyzed using competing-risk analysis. RESULTS: Implant survivorship at 15 years was 92% for cemented fixed-bearing (cemFB), 91% for uncemented mobile-bearing (uncemMB), and 80% for cemented mobile-bearing (cemMB) UKAs (p = 0.02). When compared with cemFB, the risk of revision was higher for cemMB implants (hazard ratio [HR] = 1.9, 95% confidence interval [CI] = 1.1 to 3.2; p = 0.03). At 15 years, cemented implants had a higher cumulative frequency of revision due to aseptic loosening (3% to 4%, versus 0.4% for uncemented; p < 0.01), cemMB implants had a higher cumulative frequency of revision due to osteoarthritis progression (9% versus 2% to 3% for cemFB/uncemMB; p < 0.05), and uncemMB implants had a higher cumulative frequency of revision due to bearing dislocation (4% versus 2% for cemMB; p = 0.02). Compared with the oldest patients (≥70 years), younger patients had a higher risk of revision (<60 years: HR = 1.9, 95% CI = 1.2 to 3.0; 60 to 69 years: HR = 1.6, 95% CI = 1.0 to 2.4; p < 0.05 for both). At 15 years, there was a higher cumulative frequency of revision for aseptic loosening in these younger groups (3.2% and 3.5% versus 2.7% for ≥70 years; p < 0.05). CONCLUSIONS: Implant design and patient age were risk factors for revision of medial UKA. The findings from this study suggest that surgeons should consider using cemFB or uncemMB designs because of their superior long-term implant survivorship compared with cemMB designs. Additionally, for younger patients (<70 years), uncemMB designs had a lower risk of aseptic loosening than cemFB designs at the expense of a risk of bearing dislocation. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

REST, RCOR1 and RCOR2 expression is reduced in osteoarthritic chondrocytes and contributes to increasing MMP13 and ADAMTS5 expression through upregulating HES1.

Expression of key transcriptional regulators is altered in chondrocytes in osteoarthritis (OA). This contributes to an increase in production of cartilage-catabolizing enzymes such as MMP13 and ADAMTS5. RCOR1 and RCOR2, binding partners for the transcriptional repressor REST, have previously been found to be downregulated in OA chondrocytes although their function in chondrocytes is unclear. HES1 is a known REST/RCOR1 target gene and HES1 has been shown to promote MMP13 and ADAMTS5 expression in murine OA chondrocytes. The purpose of this study was to determine whether reduced REST/RCOR levels leads to increased HES1 expression in human OA chondrocytes and whether HES1 also promotes ADAMTS5 and MMP13 expression in these cells. Chondrocytes were isolated from osteoarthritic and adjacent macroscopically normal cartilage obtained from patients undergoing total knee arthroplasty. RNA and protein levels of REST, RCOR1 and RCOR2 were lower, but levels of HES1 higher, in chondrocytes isolated from osteoarthritic compared to macroscopically normal cartilage. Over-expression of either REST, RCOR1 or RCOR2 resulted in reduced HES1 levels in OA chondrocytes whereas knockdown of REST, RCOR1 or RCOR2 led to increased HES1 expression in chondrocytes from macroscopically normal cartilage. In OA chondrocytes, ADAMTS5 and MMP13 expression were reduced following HES1 knockdown, but further enhanced following HES1 over-expression. Levels of phosphorylated CaMKII were higher in chondrocytes from OA cartilage consistent with previous findings that HES1 only promotes gene transcription in the presence of active CaMKII. These findings identify the REST/RCOR/HES1 pathway as a contributing factor leading to increased ADAMTS5 and MMP13 expression in OA chondrocytes.