Aims. This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA. Methods. Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization. Results. A total of 46 genes were obtained from the intersection of significantly upregulated genes in osteoarthritic cartilage and the key module genes screened by WGCNA. Functional annotation analysis revealed that these genes were closely related to pathological responses associated with OA, such as inflammation and immunity. Four key dysregulated genes (cartilage acidic protein 1 (CRTAC1), iodothyronine deiodinase 2 (DIO2), angiopoietin-related protein 2 (ANGPTL2), and MAGE family member D1 (MAGED1)) were identified after using machine-learning algorithms. These genes had high diagnostic value in both the training cohort and external validation cohort (receiver operating characteristic > 0.8). The upregulated expression of these hub genes in osteoarthritic cartilage signified higher levels of immune infiltration as well as the expression of metalloproteinases and mineralization markers, suggesting harmful biological alterations and indicating that these hub genes play an important role in the pathogenesis of OA. A competing endogenous RNA network was constructed to reveal the underlying post-transcriptional regulatory mechanisms. Conclusion. The current study explores and validates a dysregulated key gene set in osteoarthritic cartilage that is capable of accurately diagnosing OA and characterizing the biological alterations in osteoarthritic cartilage; this may become a promising indicator in clinical decision-making. This study indicates that dysregulated key genes play an important role in the development and progression of OA, and may be potential therapeutic targets. Cite this article: Bone Joint Res 2024;13(2):66–82

Aims. The use of high tibial osteotomy (HTO) to delay total knee arthroplasty (TKA) in young patients with osteoarthritis (OA) and constitutional deformity remains debated. The aim of this study was to compare the long-term outcomes of TKA after HTO compared to TKA without HTO, using the time from the index OA surgery as reference (HTO for the study group, TKA for the control group). Methods. This was a case-control study of consecutive patients receiving a posterior-stabilized TKA for OA between 1996 and 2010 with previous HTO. A total of 73 TKAs after HTO with minimum ten years’ follow-up were included. Cases were matched with a TKA without previous HTO for age at the time of the HTO. All revisions were recorded. Kaplan-Meier survivorship analysis was performed using revision of metal component as the endpoint. The Knee Society Score, range of motion, and patient satisfaction were assessed. Results. Mean follow-up was 13 years (SD 3) after TKA in both groups. The 20-year Kaplan-Meier survival estimate was 98.6% in TKA post-HTO group (HTO as timing reference) and 81.4% in control group (TKA as timing reference) (p = 0.030). There was no significant difference in clinical outcomes, radiological outcomes, and complications at the last follow-up. Conclusion. At the same delay from index surgery (HTO or TKA), a strategy of HTO followed by TKA had superior knee survivorship compared to early TKA at long term in young patients. Level of evidence: III. Cite this article: Bone Jt Open 2023;4(2):62–71

Aims. As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA). Methods. Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections. Results. Experimental knees immobilized for four weeks demonstrated mean PEAs of 141°, 72°, and 79° after zero, two, and four weeks of remobilization (n = 6 per group), respectively. Experimental knees demonstrated reduced PEAs after two weeks (p < 0.001) and four weeks (p < 0.0001) of remobilization compared to controls. Following eight weeks of immobilization, experimental knees exhibited mean PEAs of 82°, 73°, and 72° after zero, two, and four weeks of remobilization, respectively. Histological analysis demonstrated no cartilage degeneration. Similar trends in biomechanical and histological properties were observed when intra-articular violation was introduced. Conclusion. This study established a novel mouse model of robust knee contracture without evidence of OA. This was appreciated consistently after eight weeks of immobilization and was irrespective of length of remobilization. As such, this arthrofibrotic model provides opportunities to investigate molecular pathways and therapeutic strategies. Cite this article: Bone Joint Res 2023;12(1):58–71

Aims. The Coronal Plane Alignment of the Knee (CPAK) classification has been developed to predict individual variations in inherent knee alignment. The impact of preoperative and postoperative CPAK classification phenotype on the postoperative clinical outcomes of total knee arthroplasty (TKA) remains elusive. This study aimed to examine the effect of postoperative CPAK classification phenotypes (I to IX), and their pre- to postoperative changes on patient-reported outcome measures (PROMs). Methods. A questionnaire was administered to 340 patients (422 knees) who underwent primary TKA for osteoarthritis (OA) between September 2013 and June 2019. A total of 231 patients (284 knees) responded. The ­Knee Society Score 2011 (KSS 2011), Knee injury and Osteoarthritis Outcome Score-12 (KOOS-12), and Forgotten Joint Score-12 (FJS-12) were used to assess clinical outcomes. Using preoperative and postoperative anteroposterior full-leg radiographs, the arithmetic hip-knee-ankle angle (aHKA) and joint line obliquity (JLO) were calculated and classified based on the CPAK classification. To investigate the impact on PROMs, multivariable regression analyses using stepwise selection were conducted, considering factors such as age at surgery, time since surgery, BMI, sex, implant use, postoperative aHKA classification, JLO classification, and changes in aHKA and JLO classifications from preoperative to postoperative. Results. The preoperative and postoperative CPAK classifications were predominantly phenotype I (155 knees; 55%) and phenotype V (73 knees; 26%), respectively. The change in the preoperative to postoperative aHKA classification was a significant negative predictive factor for KOOS-12 and FJS-12, while postoperative apex proximal JLO was a significant negative predictive factor for KSS 2011 and KOOS-12. Conclusion. In primary TKA for OA, preoperative and postoperative CPAK phenotypes were associated with PROMs. Alteration in varus/valgus alignment from preoperative to postoperative was recognized as a negative predictive factor for both KOOS-12 and FJS-12. Moreover, the postoperative apex proximal JLO was identified as a negative factor for KSS 2011 and KOOS-12. Determining the target alignment for each preoperative phenotype with reproducibility could improve PROMs. Cite this article: Bone Joint J 2024;106-B(10):1059–1066

Aims. Despite new technologies for total knee arthroplasty (TKA), approximately 20% of patients are dissatisfied. A major reason for dissatisfaction and revision surgery after TKA is persistent pain. The radiological grade of osteoarthritis (OA) preoperatively has been investigated as a predictor of the outcome after TKA, with conflicting results. The aim of this study was to determine if there is a difference in the intensity of pain 12 months after TKA in relation to the preoperative radiological grade of OA alone, and the combination of the intensity of preoperative pain and radiological grade of OA. Methods. The preoperative data of 300 patients who underwent primary TKA were collected, including clinical information (age, sex, preoperative pain), psychological variables (depression, anxiety, pain catastrophizing, anticipated pain), and quantitative sensory testing (temporal summation, pressure pain thresholds, conditioned pain modulation). The preoperative radiological severity of OA was graded according to the Kellgren-Lawrence (KL) classification. Persistent pain in the knee was recorded 12 months postoperatively. Generalized linear models explored differences in postoperative pain according to the KL grade, and combined preoperative pain and KL grade. Relative risk models explored which preoperative variables were associated with the high preoperative pain/low KL grade group. Results. Pain 12 months after TKA was not associated with the preoperative KL grade alone. Significantly increased pain 12 months after TKA was found in patients with a combination of high preoperative pain and a low KL grade (p = 0.012). Patients in this group were significantly more likely to be male, younger, and have higher preoperative pain catastrophizing, higher depression, and lower anxiety (all p ≤ 0.05). Conclusion. Combined high preoperative pain and low radiological grade of OA, but not the radiological grade alone, was associated with a higher intensity of pain 12 months after primary TKA. This group may have a more complex cause of pain that requires additional psychological interventions in order to optimize the outcome of TKA. Cite this article: Bone Joint J 2022;104-B(11):1202–1208

Aims. To assess the incidence of radiological lateral osteoarthritis (OA) at 15 years after medial unicompartmental knee arthroplasty (UKA) and assess the relationship of lateral OA with symptoms and patient characteristics. Methods. Cemented Phase 3 medial Oxford UKA implanted by two surgeons since 1998 for the recommended indications were prospectively followed. A 15-year cumulative revision rate for lateral OA of 5% for this series was previously reported. A total of 163 unrevised knees with 15-year (SD 1) anterior-posterior knee radiographs were studied. Lateral joint space width (JSW. L. ) was measured and severity of lateral OA was classified as: nil/mild, moderate, and severe. Preoperative and 15-year Oxford Knee Scores (OKS) and American Knee Society Scores were determined. The effect of age, sex, BMI, and intraoperative findings was analyzed. Statistical analysis included one-way analysis of variance and Kruskal-Wallis H test, with significance set at 5%. Results. The mean age was 80.6 years (SD 8.3), with 84 females and 79 males. The mean JSW. L. was 5.6 mm (SD 1.4), and was not significantly related to age, sex, or intraoperative findings. Those with BMI > 40 kg/m. 2. had a smaller JSW. L. than those with a ‘normal’ BMI (p = 0.039). The incidence of severe and moderate lateral OA were both 4.9%. Overall, 2/142 (1.4%) of those with nil/mild lateral OA, 1/8 (13%) with moderate, and 2/8 (25%) with severe subsequently had a revision. Those with severe (mean OKS 35.6 (SD 9.3)) and moderate OA (mean OKS 35.8 (SD 10.5)) tended to have worse outcome scores than those with nil/mild (mean OKS 39.5 (SD 9.2)) but the difference was only significant for OKS-Function (p = 0.044). Conclusion. This study showed that the rate of having severe or moderate radiological lateral OA at 15 years after medial UKA was low (both 4.9%). Although patients with severe or moderate lateral OA had a lower OKS than those with nil/mild OA, their mean scores (OKS 36) would be classified as good. Cite this article: Bone Jt Open 2023;4(3):210–218

Aims. Hereditary haemochromatosis is a genetic disorder that is caused by several known mutations in the human homeostatic iron regulator protein (HFE) gene. Abnormal accumulation of iron causes a joint disease that resembles osteoarthritis (OA), but appears at a relatively younger age and is accompanied by cirrhosis, diabetes, and injury to other organs. Increased serum transferrin saturation and ferritin levels are known markers of haemochromatosis with high positive predictive values. Methods. We have retrospectively analyzed the iron studies of a cohort of 2,035 patients undergoing knee joint arthroplasty due to OA. Results. No patients had HFE gene C282Y, S65C, or H63D mutations testing. In total, 18 patients (2.96%) of the male cohort and 51 (3.58%) of the female cohort had pathologically increased ferritin levels that may be indicative of haemochromatosis. Seven patients (0.34%) had serum transferrin saturation above 45%. Conclusion. The awareness for the diagnosis of this disorder in Orthopaedics is low and needs improvement. Osteoarthritic patients undergoing knee arthroplasty should be routinely screened for haemochromatosis by iron studies and referred to genetic testing when needed. Level of evidence: Level III - Retrospective cohort study. Cite this article: Bone Jt Open 2021;2(12):1062–1066

Aims. The aim of this study was to investigate the distribution of phenotypes in Asian patients with end-stage osteoarthritis (OA) and assess whether the phenotype affected the clinical outcome and survival of mechanically aligned total knee arthroplasty (TKA). We also compared the survival of the group in which the phenotype unintentionally remained unchanged with those in which it was corrected to neutral. Methods. The study involved 945 TKAs, which were performed in 641 patients with primary OA, between January 2000 and January 2009. These were classified into 12 phenotypes based on the combined assessment of four categories of the arithmetic hip-knee-ankle angle and three categories of actual joint line obliquity. The rates of survival were analyzed using Kaplan-Meier methods and the log-rank test. The Hospital for Special Surgery score and survival of each phenotype were compared with those of the reference phenotype with neutral alignment and a parallel joint line. We also compared long-term survival between the unchanged phenotype group and the corrected to neutral alignment-parallel joint line group in patients with Type IV-b (mild to moderate varus alignment-parallel joint line) phenotype. Results. The most common phenotype was Type I-b (mild to moderate varus alignment-medial joint line; 27.1% (n = 256)), followed by Type IV-b (23.2%; n = 219). There was no significant difference in the clinical outcomes and long-term survival between the groups. In Type IV-b phenotypes, the neutrally corrected group showed higher 15-year survival compared with the unchanged-phenotype group (94.9% (95% confidence interval (CI) 92.0 to 97.8) vs 74.2% (95% CI 98.0 to 100); p = 0.020). Conclusion. Constitutional varus was confirmed in more than half of these patients. Mechanically aligned TKA can achieve consistent clinical outcomes and long-term survival, regardless of the patient’s phenotype. The neutrally corrected group had better long-term survival compared with the unchanged phenotype group. Cite this article: Bone Joint J 2024;106-B(5):460–467

Aims. Many patients undergoing total knee arthroplasty (TKA) have severe osteoarthritis (OA) in both knees and may consider either simultaneous or staged bilateral TKA. The implications of simultaneous versus staged bilateral TKA for return to work are not well understood. We hypothesized that employed patients who underwent simultaneous bilateral TKA would have significantly fewer days missed from work compared with the sum of days missed from each operation for patients who underwent staged bilateral TKA. Methods. The prospective arthroplasty registry at the Hospital for Special Surgery was used. Baseline characteristics and patient-reported outcome scores were evaluated. We used a linear regression model, adjusting for potential confounding variables including age, sex, preoperative BMI, and type of work (sedentary, moderate, high activity, or strenuous), to analyze time lost from work after simultaneous compared with staged bilateral TKA. Results. We identified 152 employed patients who had undergone simultaneous bilateral TKA and 61 who had undergone staged bilateral TKA, and had completed the registry’s return to work questionnaire. The simultaneous group missed a mean of 46.2 days (SD 29.1) compared with the staged group who missed a mean total of 68.0 days of work (SD 46.1) when combining both operations. This difference was statistically significant (p < 0.001). In multivariate mixed regression analysis adjusted for age, sex, BMI, American Society of Anesthesiologists status, and type of work, the simultaneous group missed a mean of 16.9 (SD 5.7) fewer days of work compared with the staged group (95% confidence interval 5.8 to 28.1; p = 0.003). Conclusion. Employed patients undergoing simultaneous bilateral TKA missed a mean of 17 fewer days of work as a result of their surgical treatment and rehabilitation compared with those undergoing staged bilateral TKA. This information may be useful to surgeons counselling employed patients with bilateral OA of the knee who are considering surgical treatment. Cite this article: Bone Joint J 2021;103-B(6 Supple A):108–112

Aims. The patient-acceptable symptom state (PASS) is a level of wellbeing, which is measured by the patient. The aim of this study was to determine if the proportion of patients who achieved an acceptable level of function (PASS) after medial unicompartmental knee arthroplasty (UKA) was different based on the status of the anterior cruciate ligament (ACL) at the time of surgery. Methods. A total of 114 patients who underwent UKA for isolated medial osteoarthritis (OA) of the knee were included in the study. Their mean age was 65 years (SD 10). No patient underwent a bilateral procedure. Those who had undergone ACL reconstruction during the previous five years were excluded. The Knee injury Osteoarthritis Outcome Score Activities of Daily Living (KOOS ADL) function score was used as the primary outcome measure with a PASS of 87.5, as described for total knee arthroplasty (TKA). Patients completed all other KOOS subscales, Lysholm score, the Western Ontario and McMaster Universities Osteoarthritis Index, and the Veterans Rand 12-item health survey score. Failure was defined as conversion to TKA. Results. Survivorship at ten years was 97% in both the ACL-deficient and ACL-intact groups. The mean survival was 16.1 years (95% confidence interval (CI) 15.3 to 16.8) for the ACL-deficient group and 15.6 years (95% CI 14.8 to 16.361) for the ACL-intact group (p = 0.878). At a mean of nine years (SD 3.5) in the ACL-deficient group, 32 patients (87%) reached the PASS for the KOOS ADL. In the ACL-intact group, at a mean of 8.6 years (SD 3) follow-up, 63 patients (85%) reached PASS for the KOOS ADL. There was no significant difference in the percentage of patients who reached PASS for all KOOS subscales and Lysholm between the two groups. Conclusion. PASS was achieved in 85% of all UKAs for KOOS ADL, similar to reports for TKA. Fixed-bearing, medial, non-robotically-assisted UKA resulted in 97% survival at ten years in both the ACL-deficient and ACL-intact groups. There was no significant difference in all outcomes between the two groups. Understanding PASS will allow better communication between surgeons and patients to improve the surgical management of patients with single compartment OA of the knee. This study provides mid- to long-term data supporting the use of PASS to document outcomes following UKA. PASS was met in more than 85% of patients with no differences between ACL-deficient and ACL-intact knees at a mean follow-up of nine years. Cite this article: Bone Joint J 2021;103-B(8):1367–1372

Aims. Unicompartmental knee arthroplasty (UKA) has become a popular method of treating knee localized osteoarthritis (OA). Additionally, the posterior cruciate ligament (PCL) is essential to maintaining the physiological kinematics and functions of the knee joint. Considering these factors, the purpose of this study was to investigate the biomechanical effects on PCL-deficient knees in medial UKA. Methods. Computational simulations of five subject-specific models were performed for intact and PCL-deficient UKA with tibial slopes. Anteroposterior (AP) kinematics and contact stresses of the patellofemoral (PF) joint and the articular cartilage were evaluated under the deep-knee-bend condition. Results. As compared to intact UKA, there was no significant difference in AP translation in PCL-deficient UKA with a low flexion angle, but AP translation significantly increased in the PCL-deficient UKA with high flexion angles. Additionally, the increased AP translation became decreased as the posterior tibial slope increased. The contact stress in the PF joint and the articular cartilage significantly increased in the PCL-deficient UKA, as compared to the intact UKA. Additionally, the increased posterior tibial slope resulted in a significant decrease in the contact stress on PF joint but significantly increased the contact stresses on the articular cartilage. Conclusion. Our results showed that the posterior stability for low flexion activities in PCL-deficient UKA remained unaffected; however, the posterior stability for high flexion activities was affected. This indicates that a functional PCL is required to ensure normal stability in UKA. Additionally, posterior stability and PF joint may reduce the overall risk of progressive OA by increasing the posterior tibial slope. However, the excessive posterior tibial slope must be avoided. Cite this article: Bone Joint Res 2020;9(9):593–600

Aims. The aims of this study were to investigate the ability to kneel after total knee arthroplasty (TKA) without patellar resurfacing, and its effect on patient-reported outcome measures (PROMs). Secondary aims included identifying which kneeling positions were most important to patients, and the influence of radiological parameters on the ability to kneel before and after TKA. Methods. This prospective longitudinal study involved 209 patients who underwent single radius cruciate-retaining TKA without patellar resurfacing. Preoperative EuroQol five-dimension questionnaire (EQ-5D), Oxford Knee Score (OKS), and the ability to achieve four kneeling positions were assessed including a single leg kneel, a double leg kneel, a high-flexion kneel, and a praying position. The severity of radiological osteoarthritis (OA) was graded and the pattern of OA was recorded intraoperatively. The flexion of the femoral component, posterior condylar offset, and anterior femoral offset were measured radiologically. At two to four years postoperatively, 151 patients with a mean age of 70.0 years (SD 9.44) were included. Their mean BMI was 30.4 kg/m. 2. (SD 5.36) and 60 were male (40%). They completed EQ-5D, OKS, and Kujala scores, assessments of the ability to kneel, and a visual analogue scale for anterior knee pain and satisfaction. Results. The ability to kneel in the four positions improved in between 29 (19%) and 53 patients (35%) after TKA, but declined in between 35 (23%) and 46 patients (30%). Single-leg kneeling was most important to patients. After TKA, 62 patients (41%) were unable to achieve a single-leg kneel, 76 (50%) were unable to achieve a double-leg kneel, 102 (68%) were unable to achieve a high-flexion kneel and 61 (40%) were unable to achieve a praying position. Posterolateral cartilage loss significantly affected preoperative deep flexion kneeling (p = 0.019). A postoperative inability to kneel was significantly associated with worse OKS, Kujala scores, and satisfaction (p < 0.05). Multivariable regression analysis identified significant independent associations with the ability to kneel after TKA (p < 0.05): better preoperative EQ-5D and flexion of the femoral component for single-leg kneeling; the ability to achieve it preoperatively and flexion of the femoral component for double-leg kneeling; male sex for high-flexion kneeling; and the ability to achieve it preoperatively, anterior femoral offset, and patellar cartilage loss for the praying position. Conclusion. The ability to kneel was important to patients and significantly influenced knee-specific PROMs, but was poorly restored by TKA with equal chances of improvement or decline. Cite this article: Bone Joint J 2021;103-B(9):1514–1525

Aim. There has been a significant reduction in unicompartmental knee arthroplasty (UKA) procedures recorded in Australia. This follows several national joint registry studies documenting high UKA revision rates when compared to total knee arthroplasty (TKA). With the recent introduction of robotically assisted UKA procedures, it is hoped that outcomes improve. This study examines the cumulative revision rate of UKA procedures implanted with a newly introduced robotic system and compares the results to one of the best performing non-robotically assisted UKA prostheses, as well as all other non-robotically assisted UKA procedures. Methods. Data from the Australian Orthopaedic Association National Joint Arthroplasty Registry (AOANJRR) for all UKA procedures performed for osteoarthritis (OA) between 2015 and 2018 were analyzed. Procedures using the Restoris MCK UKA prosthesis implanted using the Mako Robotic-Arm Assisted System were compared to non-robotically assisted Zimmer Unicompartmental High Flex Knee System (ZUK) UKA, a commonly used UKA with previously reported good outcomes and to all other non-robotically assisted UKA procedures using Cox proportional hazard ratios (HRs) and Kaplan-Meier estimates of survivorship. Results. There was no difference in the rate of revision when the Mako-assisted Restoris UKA was compared to the ZUK UKA (zero to nine months: HR 1.14 (95% CI 0.71 to 1.83; p = 0.596) vs nine months and over: HR 0.66 (95% CI 0.42 to 1.02; p = 0.058)). The Mako-assisted Restoris had a significantly lower overall revision rate compared to the other types of non-robotically assisted procedures (HR 0.58 (95% confidence interval (CI) 0.42 to 0.79); p < 0.001) at three years. Revision for aseptic loosening was lower for the Mako-assisted Restoris compared to all other non-robotically assisted UKA (entire period: HR 0.34 (95% CI 0.17 to 0.65); p = 0.001), but not the ZUK prosthesis. However, revision for infection was significantly higher for the Mako-assisted Restoris compared to the two comparator groups (ZUK: entire period: HR 2.91 (95% CI 1.22 to 6.98; p = 0.016); other non-robotically assisted UKA: zero to three months: HR 5.57 (95% CI 2.17 to 14.31; p < 0.001)). Conclusion. This study reports comparable short-term survivorship for the Mako robotically assisted UKA compared to the ZUK UKA and improved survivorship compared to all other non-robotic UKA. These results justify the continued use and investigation of this procedure. However, the higher rate of early revision for infection for robotically assisted UKA requires further investigation. Cite this article: Bone Joint J 2020;102-B(3):319–328

Aims. Patients with a deformity of the hindfoot present a particular challenge when performing total knee arthroplasty (TKA). The literature contains little information about the relationship between TKA and hindfoot alignment. This systematic review aimed to determine from both clinical and radiological studies whether TKA would alter a preoperative hindfoot deformity and whether the outcome of TKA is affected by the presence of a postoperative hindfoot deformity. Methods. A systematic literature search was performed in the databases PubMed, EMBASE, Cochrane Library, and Web of Science. Search terms consisted of “total knee arthroplasty/replacement” combined with “hindfoot/ankle alignment”. Inclusion criteria were all English language studies analyzing the association between TKA and the alignment of the hindfoot, including the clinical or radiological outcomes. Exclusion criteria consisted of TKA performed with a concomitant extra-articular osteotomy and case reports or expert opinions. An assessment of quality was conducted using the modified Methodological Index for Non-Randomized Studies (MINORS). The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and registered in the PROSPERO database (CRD42019106980). Results. A total of 17 studies were found to be eligible for review. They included six prospective and ten retrospective studies, and one case-control study. The effects of TKA showed a clinical improvement in the hindfoot deformity in three studies, but did not if there was osteoarthritis (OA) of the ankle (one study) or a persistent deformity of the knee (one study). The radiological alignment of the hindfoot corrected in 11 studies, but did not in the presence of a rigid hindfoot varus deformity (in two studies). The effects of a hindfoot deformity on TKA included a clinical association with instability of the knee in one study, and a shift in the radiological weightbearing axis in two studies. The mean MINORS score was 9.4 out of 16 (7 to 12). Conclusion. TKA improves both the function and alignment of the hindfoot in patients with a preoperative deformity of the hindfoot. This may not apply if there is a persistent deformity of the knee, a rigid hindfoot varus deformity, or OA of the ankle. Moreover, a persistent deformity of the hindfoot may adversely affect the stability and longevity of a TKA. These findings should be interpreted with caution due to the moderate methodological quality of the studies which were included. Therefore, further prospective studies are needed in order to determine at which stage correction of a hindfoot deformity is required to optimize the outcome of a TKA. Cite this article: Bone Joint J 2021;103-B(1):87–97

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

Aims. Altered alignment and biomechanics are thought to contribute to the progression of osteoarthritis (OA) in the native compartments after medial unicompartmental knee arthroplasty (UKA). The aim of this study was to evaluate the bone activity and remodelling in the lateral tibiofemoral and patellofemoral compartment after medial mobile-bearing UKA. Patients and Methods. In total, 24 patients (nine female, 15 male) with 25 medial Oxford UKAs (13 left, 12 right) were prospectively followed with sequential 99mTc-hydroxymethane diphosphonate single photon emission CT (SPECT)/CT preoperatively and at one and two years postoperatively, along with standard radiographs and clinical outcome scores. The mean patient age was 62 years (40 to 78) and the mean body mass index (BMI) was 29.7 kg/m2 (23.6 to 42.2). Mean osteoblastic activity was evaluated using a tracer localization scheme with volumes of interest (VOIs). Normalized mean tracer values were calculated as the ratio between the mean tracer activity in a VOI and background activity in the femoral diaphysis. Results. Significant reduction of normalized tracer activity was observed one year postoperatively in tibial and femoral VOIs adjacent to the joint line in the lateral compartment. Patellar VOIs and remaining femoral VOIs demonstrated a significant, diminished normalized tracer activity at final follow-up. Conclusion. The osteoblastic bone activity in the native compartments decreased significantly after treatment of medial end-stage OA with a UKA, implying reduced stress to the subchondral bone in the retained compartments after a UKA. Cite this article: Bone Joint J 2019;101-B:915–921

Aims. Limited evidence is available on mid-term outcomes of robotic-arm assisted (RA) partial knee arthroplasty (PKA). Therefore, the purpose of this study was to evaluate mid-term survivorship, modes of failure, and patient-reported outcomes of RA PKA. Methods. A retrospective review of patients who underwent RA PKA between June 2007 and August 2016 was performed. Patients received a fixed-bearing medial or lateral unicompartmental knee arthroplasty (UKA), patellofemoral arthroplasty (PFA), or bicompartmental knee arthroplasty (BiKA; PFA plus medial UKA). All patients completed a questionnaire regarding revision surgery, reoperations, and level of satisfaction. Knee Injury and Osteoarthritis Outcome Scores (KOOS) were assessed using the KOOS for Joint Replacement Junior survey. Results. Mean follow-up was 4.7 years (2.0 to 10.8). Five-year survivorship of medial UKA (n = 802), lateral UKA (n = 171), and PFA/BiKA (n = 35/10) was 97.8%, 97.7%, and 93.3%, respectively. Component loosening and progression of osteoarthritis (OA) were the most common reasons for revision. Mean KOOS scores after medial UKA, lateral UKA, and PFA/BiKA were 84.3 (SD 15.9), 85.6 (SD 14.3), and 78.2 (SD 14.2), respectively. The vast majority of the patients reported high satisfaction levels after RA PKA. Subgroup analyses suggested tibial component design, body mass index (BMI), and age affects RA PKA outcomes. Five-year survivorship was 98.4% (95% confidence interval (CI) 97.2 to 99.5) for onlay medial UKA (n = 742) and 99.1% (95% CI 97.9 to 100) for onlay medial UKA in patients with a BMI < 30 kg/m. 2. (n = 479). Conclusion. This large single-surgeon study showed high mid-term survivorship, satisfaction levels, and functional outcomes in RA UKA using metal-backed tibial onlay components. In addition, favourable results were reported in RA PFA and BiKA. Cite this article: Bone Joint J 2020;102-B(1):108–116

Aim. Mesenchymal stem cells (MSCs) have several properties that may support their use as an early treatment option for osteoarthritis (OA). This study investigated the role of multiple injections of allogeneic bone marrow-derived stem cells (BMSCs) to alleviate the progression of osteoarthritic changes in the various structures of the mature rabbit knee in an anterior cruciate ligament (ACL)-deficient OA model. Materials and Methods. Two months after bilateral section of the ACL of Japanese white rabbits aged nine months or more, either phosphate buffered saline (PBS) or 1 x 10. 6. MSCs were injected into the knee joint in single or three consecutive doses. After two months, the articular cartilage and meniscus were assessed macroscopically, histologically, and immunohistochemically using collagen I and II. Results. Within the PBS injection (control group), typical progressive degenerative changes were revealed in the various knee structures. In the single MSC injection (single group), osteoarthritic changes were attenuated, but still appeared, especially in the medial compartments involving fibrillation of the articular cartilage, osteophyte formation in the medial plateau, and longitudinal tear of the meniscus. In the multiple-injections group, the smoothness and texture of the articular cartilage and meniscus were improved. Histologically, absence or reduction in matrix staining and cellularity were noticeable in the control and single-injection groups, respectively, in contrast to the multiple-injections group, which showed good intensity of matrix staining and chondrocyte distribution in the various cartilage zones. Osteoarthritis Research Society International (OARSI) scoring showed significantly better results in the multiple-injections group than in the other groups. Immunohistochemically, collagen I existed superficially in the medial femoral condyle in the single group, while collagen II was more evident in the multiple-injections group than the single-injection group. Conclusion. A single injection of MSCs was not enough to restore the condition of osteoarthritic joints. This is in contrast to multiple injections of MSCs, which had the ability to replace lost cells, as well as reducing inflammation. Cite this article: Bone Joint J 2019;101-B:824–831

Objectives. Previous genome-wide association studies (GWAS) have reported significant association of the single nucleotide polymorphism (SNP) rs8044769 in the fat mass and obesity-associated gene (FTO) with osteoarthritis (OA) risk in European populations. However, these findings have not been confirmed in Chinese populations. Methods. We systematically genotyped rs8044769 and evaluated the association between the genetic variants and OA risk in a case-controlled study including 196 OA cases and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Results. We found that the variant T allele of rs8044769 showed no significant association of OA risk (p = 0.791), or association with body mass index (BMI) (pmeta = 0.786) in an additive genetic model. However, we detected a significant interaction between rs8044769 genotypes and BMI on OA risk (p = 0.037), as well as a borderline interaction between rs8044769 genotypes and age on OA risk (p = 0.062). Conclusions. Our findings indicate that rs8044769 in the FTO gene may not modify individual susceptibility to OA or increased BMI in the Chinese population. Further studies are warranted to validate and extend our findings. Cite this article: Prof L. Jiang. No association of the single nucleotide polymorphism rs8044769 in the fat mass and obesity-associated gene with knee osteoarthritis risk and body mass index: A population-based study in China. Bone Joint Res 2016;5:169–174. DOI: 10.1302/2046-3758.55.2000589

Aims. To report mid- to long-term results of Oxford mobile bearing domed lateral unicompartmental knee arthroplasty (UKA), and determine the effect of potential contraindications on outcome. Methods. A total of 325 consecutive domed lateral UKAs undertaken for the recommended indications were included, and their functional and survival outcomes were assessed. The effects of age, weight, activity, and the presence of full-thickness erosions of cartilage in the patellofemoral joint on outcome were evaluated. Results. Median follow-up was seven years (3 to 14), and mean age at surgery was 65 years (39 to 90). Median Oxford Knee Score (OKS) was 43 (interquartile range (IQR) 37 to 47), with 260 (80%) achieving a good or excellent score (OKS > 34). Revisions occurred in 34 (10%); 14 (4%) were for dislocation, of which 12 had no recurrence following insertion of a new bearing, and 12 (4%) were revised for medial osteoarthritis (OA). Ten-year survival was 85% (95% confidence interval (CI) 79 to 90, at risk 72). Age, weight, activity, and patellofemoral erosions did not have a significant effect on the clinical outcome or survival. Conclusion. Domed lateral UKA provides a good alternative to total knee arthroplasty (TKA) in the management of lateral compartment OA. Although dislocation is relatively easy to treat successfully, the dislocation rate of 4% is high. It is recommended that the stability of the bearing is assessed intraoperatively. If the bearing can easily be displaced, the fixed rather than the mobile bearing version of the Oxford lateral tibial component should be inserted instead. Younger age, heavier weight, high activity, and patellofemoral erosions did not detrimentally affect outcome, so should not be considered contraindications. Cite this article: Bone Joint J 2020;102-B(8):1033–1040