Aims. The aim of this study was to analyze the results of two radiocapitellar prostheses in a large case series followed prospectively, with medium-term follow-up. Patients and Methods. A total of 31 patients with a mean age of 54 years (27 to 73) were analyzed; nine had primary osteoarthritis (OA) and 17 had post-traumatic OA, three had capitellar osteonecrosis, and two had a fracture. Overall, 17 Lateral Resurfacing Elbow (LRE) and 14 Uni-Elbow Radio-Capitellum Implant (UNI-E) arthroplasties were performed. Pre- and postoperative assessment involved the Mayo Elbow Performance Score (MEPS), the Quick Disabilities of the Arm, Shoulder and Hand (Q-DASH) score, and the modified American Shoulder Elbow Surgeons (m-ASES) score. Results. The mean follow-up was 6.8 years (3.8 to 11.5). The mean MEPS, m-ASES, and Q-DASH scores improved significantly by 50 (p < 0.001), 55 (p < 0.001), and 54 points (p < 0.001), respectively, with no differences being detected between the implants. Preoperative pronation and supination were worse in patients in whom the UNI-E was used. Two patients with the UNI-E implant had asymptomatic evidence of gross loosening. Conclusion. Radiocapitellar arthroplasty yielded a significant improvement in elbow function at a mean follow-up of 6.8 years, with a high implant survival rate when the LRE was used in patients with primary or post-traumatic OA, without radial head deformity, and when the UNI-E was used in patients in whom radial head excision was indicated. Cite this article: Bone Joint J 2019;101-B:1362–1369

Aims. The lack of disease-modifying treatments for osteoarthritis (OA) is linked to a shortage of suitable biomarkers. This study combines multi-molecule synovial fluid analysis with machine learning to produce an accurate diagnostic biomarker model for end-stage knee OA (esOA). Methods. Synovial fluid (SF) from patients with esOA, non-OA knee injury, and inflammatory knee arthritis were analyzed for 35 potential markers using immunoassays. Partial least square discriminant analysis (PLS-DA) was used to derive a biomarker model for cohort classification. The ability of the biomarker model to diagnose esOA was validated by identical wide-spectrum SF analysis of a test cohort of ten patients with esOA. Results. PLS-DA produced a streamlined biomarker model with excellent sensitivity (95%), specificity (98.4%), and reliability (97.4%). The eight-biomarker model produced a fingerprint for esOA comprising type IIA procollagen N-terminal propeptide (PIIANP), tissue inhibitor of metalloproteinase (TIMP)-1, a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), monocyte chemoattractant protein (MCP)-1, interferon-γ-inducible protein-10 (IP-10), and transforming growth factor (TGF)-β3. Receiver operating characteristic (ROC) analysis demonstrated excellent discriminatory accuracy: area under the curve (AUC) being 0.970 for esOA, 0.957 for knee injury, and 1 for inflammatory arthritis. All ten validation test patients were classified correctly as esOA (accuracy 100%; reliability 100%) by the biomarker model. Conclusion. SF analysis coupled with machine learning produced a partially validated biomarker model with cohort-specific fingerprints that accurately and reliably discriminated esOA from knee injury and inflammatory arthritis with almost 100% efficacy. The presented findings and approach represent a new biomarker concept and potential diagnostic tool to stage disease in therapy trials and monitor the efficacy of such interventions. Cite this article: Bone Joint Res 2020;9(9):623–632

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. We report the medium-term outcomes of a consecutive series of 118 Zenith total ankle arthroplasties (TAAs) from a single, non-designer centre. Methods. Between December 2010 and May 2016, 118 consecutive Zenith prostheses were implanted in 114 patients. Demographic, clinical, and patient-reported outcome measures (PROMs) data were collected. The endpoint of the study was failure of the implant requiring revision of one or all of the components. Kaplan-Meier survival curves were generated with 95% confidence intervals (CIs) and the rate of failure calculated for each year. Results. Eight patients (ten ankles) died during follow-up, but none required revision. Of the surviving 106 patients (108 ankles: rheumatoid arthritis (RA), n = 15; osteoarthritis (OA), n = 93), 38 were women and 68 were men, with a mean age of 68.2 years (48 to 86) at the time of surgery. Mean follow-up was 5.1 years (2.1 to 9.0). A total of ten implants failed (8.5%), thus requiring revision. The implant survival at seven years, using revision as an endpoint, was 88.2% (95% CI 100% to 72.9%). There was a mean improvement in Manchester-Oxford Foot and Ankle Questionnaire (MOXFQ) from 85.0 to 32.8 and visual analogue scale (VAS) scores from 7.0 to 3.2, and overall satisfaction was 89%. The three commonest complications were malleolar fracture (14.4%, n = 17), wound healing (13.6%, n = 16), and superficial infection (12.7%, n = 15). The commonest reason for revision was aseptic loosening. No patients in our study were revised for deep infection. Conclusion. Our results show that Zenith survival rates are comparable with those in the literature for other implants and in the National Joint Registry (NJR). Overall patient satisfaction was high as were functional outcomes. However, the data highlight potential complications associated with this surgery. The authors believe that these figures support ankle arthroplasty as an option in the treatment of ankle arthritis. Cite this article: Bone Joint J 2021;103-B(4):696–703

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

Aims. The aim of this study was to report the long-term results of rotational acetabular osteotomy (RAO) for symptomatic hip dysplasia in patients aged younger than 21 years at the time of surgery. Patients and Methods. We evaluated 31 patients (37 hips) aged younger than 21 years at the time of surgery retrospectively. There were 29 female and two male patients. Their mean age at the time of surgery was 17.4 years (12 to 21). The mean follow-up was 17.9 years (7 to 30). The RAO was combined with a varus or valgus femoral osteotomy or a greater trochanteric displacement in eight hips, as instability or congruence of the hip could not be corrected adequately using RAO alone. Results. The mean Merle d’Aubigné clinical score improved significantly from 15.4 to 17.2 (p < 0.0001). The mean centre-edge (CE) angle improved from -2.6° to 26°, the mean acetabular roof angle improved from 3.0° to 5.2°, and the mean head lateralization index improved from 0.68 to 0.62. Progression of radiological osteoarthritis (OA) was seen in seven hips, but no patient underwent total hip arthroplasty. Conclusion. RAO is an effective form of correction for a severely dysplastic hip in adolescent and young adult patients. Cite this article: Bone Joint J 2019;101-B:390–395

Aims. The aim of this study was to examine whether hips with unilateral osteoarthritis (OA) secondary to developmental dysplasia of the hip (DDH) have significant asymmetry in femoral length, and to determine potential related factors. Patients and Methods. We enrolled 90 patients (82 female, eight male) with DDH showing unilateral OA changes, and 43 healthy volunteers (26 female, 17 male) as controls. The mean age was 61.8 years (39 to 93) for the DDH groups, and 71.2 years (57 to 84) for the control group. Using a CT-based coordinate measurement system, we evaluated the following vertical distances: top of the greater trochanter to the knee centre (femoral length GT), most medial prominence of the lesser trochanter to the knee centre (femoral length LT), and top of the greater trochanter to the medial prominence of the lesser trochanter (intertrochanteric distance), along with assessments of femoral neck anteversion and neck shaft angle. Results. The percentages of hips with an absolute difference of > 5 mm in femoral GT and LT lengths were significantly larger in the DDH group (24% for both) compared with those of the control group (2% and 7%, respectively). The femoral length GT of the affected femur was significantly shorter in Crowe I and longer in Crowe IV than that of the unaffected side. The affected-to-unaffected difference of the intertrochanteric distance showed positive correlation with that of the femoral length GT in Crowe I and Crowe II/III, and negative correlation with that of the femoral length LT in the Crowe I and Crowe IV groups. Conclusion. Hips with unilateral end-stage OA secondary to DDH show significant asymmetry in femoral length between both the greater and lesser trochanter and the knee compared with controls. The intertrochanteric distance was a morphological factor related to femoral-length asymmetry. When undertaking total hip arthroplasty (THA) in the presence of DDH, long leg radiographs or CT measurements should be used to assess true leg-length discrepancy. Cite this article: Bone Joint J 2019;101-B:297–302

Aims. The aim of this study was to systematically review the literature for evidence of the effect of a high-fat diet (HFD) on the onset or progression of osteoarthritis (OA) in mice. Methods. A literature search was performed in PubMed, Embase, Web of Science, and Scopus to find all studies on mice investigating the effects of HFD or Western-type diet on OA when compared with a control diet (CD). The primary outcome was the determination of cartilage loss and alteration. Secondary outcomes regarding local and systemic levels of proteins involved in inflammatory processes or cartilage metabolism were also examined when reported. Results. In total, 14 publications met our inclusion criteria and were included in our review. Our meta-analysis showed that, when measured by the modified Mankin Histological-Histochemical Grading System, there was a significantly higher rate of OA in mice fed a HFD than in mice on a CD (standardized mean difference (SMD) 1.27, 95% confidence interval (CI) 0.63 to 1.91). Using the Osteoarthritis Research Society International (OARSI) score, there was a trend towards HFD causing OA (SMD 0.78, 95% CI -0.04 to 1.61). In terms of OA progression, a HFD consistently worsened the progression of surgically induced OA when compared with a CD. Finally, numerous inflammatory cytokines such as tumour necrosis factor alpha (TNF-α), interleukin (IL)-1β, and leptin, among others, were found to be altered by a HFD. Conclusion. A HFD seems to induce or exacerbate the progression of OA in mice. The metabolic changes and systemic inflammation brought about by a HFD appear to be key players in the onset and progression of OA. Cite this article: Bone Joint Res 2019;8:582–592

Aims. Osteoarthritis (OA) is the most prevalent joint disease. However, the specific and definitive genetic mechanisms of OA are still unclear. Methods. Tissue-related transcriptome-wide association studies (TWAS) of hip OA and knee OA were performed utilizing the genome-wide association study (GWAS) data of hip OA and knee OA (including 2,396 hospital-diagnosed hip OA patients versus 9,593 controls, and 4,462 hospital-diagnosed knee OA patients versus 17,885 controls) and gene expression reference to skeletal muscle and blood. The OA-associated genes identified by TWAS were further compared with the differentially expressed genes detected by the messenger RNA (mRNA) expression profiles of hip OA and knee OA. Functional enrichment and annotation analysis of identified genes was performed by the DAVID and FUMAGWAS tools. Results. We detected 33 common genes, eight common gene ontology (GO) terms, and one common pathway for hip OA, such as calcium and integrin-binding protein 1 (CIB1) (PTWAS = 0.025, FCmRNA = -1.575 for skeletal muscle), adrenomedullin (ADM) (PTWAS = 0.022, FCmRNA = -4.644 for blood), Golgi apparatus (PTWAS <0.001, PmRNA = 0.012 for blood), and phosphatidylinositol 3' -kinase-protein kinase B (PI3K-Akt) signalling pathway (PTWAS = 0.033, PmRNA = 0.005 for blood). For knee OA, we detected 24 common genes, eight common GO terms, and two common pathways, such as histocompatibility complex, class II, DR beta 1 (HLA-DRB1) (PTWAS = 0.040, FCmRNA = 4.062 for skeletal muscle), Follistatin-like 1 (FSTL1) (PTWAS = 0.048, FCmRNA = 3.000 for blood), cytoplasm (PTWAS < 0.001, PmRNA = 0.005 for blood), and complement and coagulation cascades (PTWAS = 0.017, PmRNA = 0.001 for skeletal muscle). Conclusion. We identified a group of OA-associated genes and pathways, providing novel clues for understanding the genetic mechanism of OA. Cite this article:Bone Joint Res. 2020;9(3):130–138

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

Objectives. The role of mechanical stress and transforming growth factor beta 1 (TGF-β1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known. Methods. In this study, TGF-β1 from osteoclasts and knee joints were analyzed using a co-cultured cell model and an OA rat model, respectively. Five patients with a femoral neck fracture (four female and one male, mean 73.4 years (68 to 79)) were recruited between January 2015 and December 2015. Results showed that TGF-β1 was significantly upregulated in osteoclasts by cyclic loading in a time- and dose-dependent mode. The osteoclasts were subjected to cyclic loading before being co-cultured with chondrocytes for 24 hours. Results. A significant decrease in the survival rate of co-cultured chondrocytes was found. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay demonstrated that mechanical stress-induced apoptosis occurred significantly in co-cultured chondrocytes but administration of the TGF-β1 receptor inhibitor, SB-505124, can significantly reverse these effects. Abdominal administration of SB-505124 can attenuate markedly articular cartilage degradation in OA rats. Conclusion. Mechanical stress-induced overexpression of TGF-β1 from osteoclasts is responsible for chondrocyte apoptosis and cartilage degeneration in OA. Administration of a TGF-β1 inhibitor can inhibit articular cartilage degradation. Cite this article: R-K. Zhang, G-W. Li, C. Zeng, C-X. Lin, L-S. Huang, G-X. Huang, C. Zhao, S-Y. Feng, H. Fang. Mechanical stress contributes to osteoarthritis development through the activation of transforming growth factor beta 1 (TGF-β1). Bone Joint Res 2018;7:587–594. DOI: 10.1302/2046-3758.711.BJR-2018-0057.R1

Aims. The primary aim of this study was to compare the hip-specific functional outcome of robotic assisted total hip arthroplasty (rTHA) with manual total hip arthroplasty (mTHA) in patients with osteoarthritis (OA). Secondary aims were to compare general health improvement, patient satisfaction, and radiological component position and restoration of leg length between rTHA and mTHA. Methods. A total of 40 patients undergoing rTHA were propensity score matched to 80 patients undergoing mTHA for OA. Patients were matched for age, sex, and preoperative function. The Oxford Hip Score (OHS), Forgotten Joint Score (FJS), and EuroQol five-dimension questionnaire (EQ-5D) were collected pre- and postoperatively (mean 10 months (SD 2.2) in rTHA group and 12 months (SD 0.3) in mTHA group). In addition, patient satisfaction was collected postoperatively. Component accuracy was assessed using Lewinnek and Callanan safe zones, and restoration of leg length were assessed radiologically. Results. There were no significant differences in the preoperative demographics (p ≥ 0.781) or function (p ≥ 0.383) between the groups. The postoperative OHS (difference 2.5, 95% confidence interval (CI) 0.1 to 4.8; p = 0.038) and FJS (difference 21.1, 95% CI 10.7 to 31.5; p < 0.001) were significantly greater in the rTHA group when compared with the mTHA group. However, only the FJS was clinically significantly greater. There was no difference in the postoperative EQ-5D (difference 0.017, 95% CI -0.042 to 0.077; p = 0.562) between the two groups. No patients were dissatisfied in the rTHA group whereas six were dissatisfied in the mTHA group, but this was not significant (p = 0.176). rTHA was associated with an overall greater rate of component positioning in a safe zone (p ≤ 0.003) and restoration of leg length (p < 0.001). Conclusion. Patients undergoing rTHA had a greater hip-specific functional outcome when compared to mTHA, which may be related to improved component positioning and restoration of leg length. However, there was no difference in their postoperative generic health or rate of satisfaction. Cite this article: Bone Joint Res 2021;10(1):22–30

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

Objectives. The aim of this study was to provide a comprehensive understanding of alterations in messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in cartilage affected by osteoarthritis (OA). Methods. The expression profiles of mRNAs, lncRNAs, and circRNAs in OA cartilage were assessed using whole-transcriptome sequencing. Bioinformatics analyses included prediction and reannotation of novel lncRNAs and circRNAs, their classification, and their placement into subgroups. Gene ontology and pathway analysis were performed to identify differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs). We focused on the overlap of DEGs and targets of DELs previously identified in seven high-throughput studies. The top ten DELs were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in articular chondrocytes, both in vitro and in vivo. Results. In total, 739 mRNAs, 1152 lncRNAs, and 42 circRNAs were found to be differentially expressed in OA cartilage tissue. Among these, we identified 18 overlapping DEGs and targets of DELs, and the top ten DELs were screened by expression profile analysis as candidate OA-related genes. WISP2, ATF3, and CHI3L1 were significantly increased in both normal versus OA tissues and normal versus interleukin (IL)-1β-induced OA-like cell models, while ADAM12, PRELP, and ASPN were shown to be significantly decreased. Among the identified DELs, we observed higher expression of ENST00000453554 and MSTRG.99593.3, and lower expression of MSTRG.44186.2 and NONHSAT186094.1 in normal versus OA cells and tissues. Conclusion. This study revealed expression patterns of coding and noncoding RNAs in OA cartilage, which added sets of genes and noncoding RNAs to the list of candidate diagnostic biomarkers and therapeutic agents for OA patients. Cite this article: H. Li, H. H. Yang, Z. G. Sun, H. B. Tang, J. K. Min. Whole-transcriptome sequencing of knee joint cartilage from osteoarthritis patients. Bone Joint Res 2019;8:290–303. DOI: 10.1302/2046-3758.87.BJR-2018-0297.R1

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

Objectives. Given the function of adiponectin (ADIPOQ) on the inflammatory condition of obesity and osteoarthritis (OA), we hypothesized that the ADIPOQ gene might be a candidate gene for a marker of susceptibility to OA. Methods. We systematically screened three tagging polymorphisms (rs182052, rs2082940 and rs6773957) in the ADIPOQ gene, and evaluated the association between the genetic variants and OA risk in a case-controlled study that included 196 OA patients and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Results. The single nucleotide polymorphism (SNP) rs182052 was found to be potentially associated with knee OA risk (additive model: odds ratio = 1.38; 95% confidence interval 1.07 to 1.76; p = 0.012). Furthermore, a non-significant association was observed for rs182052 and body mass index with regard to OA risk in interaction analyses (p = 0.063). Similarly, no significant interaction was detected for rs182052 and age with regard to OA risk (p = 0.614). Conclusion. These findings suggest that the SNP rs182052 in the ADIPOQ gene may potentially modify individual susceptibility to knee OA in the Chinese population. Further studies are warranted to investigate our findings in more depth. Cite this article: L. Jiang, X. Zhu, J. Rong, B. Xing, S. Wang, A. Liu, M. Chu, G. Huang. Obesity, osteoarthritis and genetic risk: The rs182052 polymorphism in the ADIPOQ gene is potentially associated with risk of knee osteoarthritis. Bone Joint Res 2018;7:494–500. DOI: 10.1302/2046-3758.77.BJR-2017-0274.R1

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

Objectives. Adult mice lacking the transcription factor NFAT1 exhibit osteoarthritis (OA). The precise molecular mechanism for NFAT1 deficiency-induced osteoarthritic cartilage degradation remains to be clarified. This study aimed to investigate if NFAT1 protects articular cartilage (AC) against OA by directly regulating the transcription of specific catabolic and anabolic genes in articular chondrocytes. Methods. Through a combined approach of gene expression analysis and web-based searching of NFAT1 binding sequences, 25 candidate target genes that displayed aberrant expression in Nfat1. -/-. AC at the initiation stage of OA, and possessed at least four NFAT1 binding sites in the promoter of each gene, were selected and tested for NFAT1 transcriptional activities by chromatin immunoprecipitation (ChIP) and promoter luciferase reporter assays using chondrocytes isolated from the AC of three- to four-month-old wild-type mice or Nfat1. -/-. mice with early OA phenotype. Results. Chromatin immunoprecipitation assays revealed that NFAT1 bound directly to the promoter of 21 of the 25 tested genes encoding cartilage-matrix proteins, growth factors, inflammatory cytokines, matrix-degrading proteinases, and specific transcription factors. Promoter luciferase reporter assays of representative anabolic and catabolic genes demonstrated that NFAT1-DNA binding functionally regulated the luciferase activity of specific target genes in wild-type chondrocytes, but not in Nfat1. -/-. chondrocytes or in wild-type chondrocytes transfected with plasmids containing mutated NFAT1 binding sequences. Conclusion. NFAT1 protects AC against degradation by directly regulating the transcription of target genes in articular chondrocytes. NFAT1 deficiency causes defective transcription of specific anabolic and catabolic genes in articular chondrocytes, leading to increased matrix catabolism and osteoarthritic cartilage degradation. Cite this article: M. Zhang, Q. Lu, T. Budden, J. Wang. NFAT1 protects articular cartilage against osteoarthritic degradation by directly regulating transcription of specific anabolic and catabolic genes. Bone Joint Res 2019;8:90–100. DOI: 10.1302/2046-3758.82.BJR-2018-0114.R1