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 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

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

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. 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

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. 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

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

Aims. To our knowledge, no study has compared the long-term results of cemented and hybrid total hip arthroplasty (THA) in patients with osteoarthritis (OA) secondary to congenital hip disease (CHD). This is a demanding procedure that may require special techniques and implants. Our aim was to compare the long-term outcome of cemented low-friction arthroplasty (LFA) and hybrid THA performed by one surgeon. Patients and Methods. Between January 1989 and December 1997, 58 hips (44 patients; one man, 43 woman; mean age 56.6 years (25 to 77)) with OA secondary to CHD were treated with a cemented Charnley LFA (group A), and 55 hips (39 patients; two men, 37 women; mean age 49.1 years (27 to 70)) were treated with a hybrid THA (group B), by the senior author (GH). The clinical outcome and survivorship were compared. Results. At all timepoints, group A hips had slightly better survivorship than those in group B without a statistically significant difference, except for the 24-year survival of acetabular components with revision for aseptic loosening as the endpoint, which was slightly worse. The survivorship was only significantly better in group A compared with group B when considering reoperation for any indication as the endpoint, 15 years postoperatively (74% vs 52%, p = 0.018). Conclusion. We concluded that there was not a substantial difference at almost any time in the outcome of cemented Charnley LFAs compared with hybrid THAs when treating patients with OA of the hip secondary to CHD. We believe, however, that after improvements in the design of components used in hybrid THA, this could be the method of choice, as it is technically easier with a shorter operating time. Cite this article: Bone Joint J 2019;101-B:1050–1057

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

Objectives. In this study, we compared the pain behaviour and osteoarthritis (OA) progression between anterior cruciate ligament transection (ACLT) and osteochondral injury in surgically-induced OA rat models. Methods. OA was induced in the knee joints of male Wistar rats using transection of the ACL or induction of osteochondral injury. Changes in the percentage of high limb weight distribution (%HLWD) on the operated hind limb were used to determine the pain behaviour in these models. The development of OA was assessed and compared using a histological evaluation based on the Osteoarthritis Research Society International (OARSI) cartilage OA histopathology score. Results. Both models showed an increase in joint pain as indicated by a significant (p < 0.05) decrease in the values of %HLWD at one week post-surgery. In the osteochondral injury model, the %HLWD returned to normal within three weeks, while in the ACLT model, a significant decrease in the %HLWD was persistent over an eight-week period. In addition, OA progression was more advanced in the ACLT model than in the osteochondral injury model. Furthermore, the ACLT model exhibited a higher mean OA score than that of the osteochondral injury model at 12 weeks. Conclusion. The development of pain patterns in the ACLT and osteochondral injury models is different in that the OA progression was significant in the ACLT model. Although both can be used as models for a post-traumatic injury of the knee, the selection of appropriate models for OA in preclinical studies should be specified and relevant to the clinical scenario. Cite this article: T. Tawonsawatruk, O. Sriwatananukulkit, W. Himakhun, W. Hemstapat. Comparison of pain behaviour and osteoarthritis progression between anterior cruciate ligament transection and osteochondral injury in rat models. Bone Joint Res 2018;7:244–251. DOI: 10.1302/2046-3758.73.BJR-2017-0121.R2

Aims. There is little information about how to manage patients with a recurvatum deformity of the distal tibia and osteoarthritis (OA) of the ankle. The aim of this study was to evaluate the functional and radiological outcome of addressing this deformity using a flexion osteotomy and to assess the progression of OA after this procedure. Patients and Methods. A total of 39 patients (12 women, 27 men; mean age 47 years (28 to 72)) with a distal tibial recurvatum deformity were treated with a flexion osteotomy, between 2010 and 2015. Nine patients (23%) subsequently required conversion to either a total ankle arthroplasty (seven) or an arthrodesis (two) after a mean of 21 months (9 to 36). A total of 30 patients (77%), with a mean follow-up of 30 months (24 to 76), remained for further evaluation. Functional outcome, sagittal ankle joint OA using a modified Kellgren and Lawrence Score, tibial lateral surface (TLS) angle, and talar offset ratio (TOR) were evaluated on pre- and postoperative weight-bearing radiographs. Results. Postoperatively, the mean score for pain, using a visual analogue scale, decreased significantly from 4.3 to 2.5 points and the mean American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score improved significantly from 59 to 75 points (both p < 0.001). The mean TLS angle increased significantly by 6.6°; the mean TOR decreased significantly by 0.24 (p < 0.001). Radiological evaluation showed an improvement or no progression of sagittal ankle joint OA in 32 ankles (82%), while seven ankles (18%) showed further progression. Conclusion. A flexion osteotomy effectively improved the congruency of the ankle joint. In 30 patients (77%), the joint could be saved, whereas in nine patients (23%), the treatment delayed a joint-sacrificing procedure. Cite this article: Bone Joint J 2019;101-B:682–690

Aims. This study presents the long-term survivorship, risk factors for prosthesis survival, and an assessment of the long-term effects of changes in surgical technique in a large series of patients treated by metal-on-metal (MoM) hip resurfacing arthroplasty (HRA). Patients and Methods. Between November 1996 and January 2012, 1074 patients (1321 hips) underwent HRA using the Conserve Plus Hip Resurfacing System. There were 787 men (73%) and 287 women (27%) with a mean age of 51 years (14 to 83). The underlying pathology was osteoarthritis (OA) in 1003 (75.9%), developmental dysplasia of the hip (DDH) in 136 (10.3%), avascular necrosis in 98 (7.4%), and other conditions, including inflammatory arthritis, in 84 (6.4%). Results. The mean follow-up time was 10.5 years (1 to 20). Using revision for any reason as the endpoint, the overall survivorship at 15 years was 89.4% (95% confidence interval (CI) 86.8 to 91.4). There was a substantial increase between the first and second generation of surgical technique (86.6% vs 90.1%; p = 0.05). Men with idiopathic OA had a 15-year survivorship of 94.5% and women, 82.2% (p = 0.001); gender was not a risk factor after stratification by component size and aetiology. Using revision for excessive wear (ion levels > 7 µg/l associated with symptoms or adverse local tissue reactions) as the endpoint, the 15-year survivorship was 98.5%. Risk factors for revision for all modes of failure were an underlying pathology of hip dysplasia, a contact patch to rim (CPR) distance of 7 mm or less, an age at surgery of 55 years or less, and a femoral component size of 46 mm or less. Specific risk factors for aseptic failure of the femoral component were early surgical technique, a cementless metaphyseal stem, and a body mass index of 24 kg/m. 2. or less. Conclusion. HRA is a viable concept; metal-on-metal bearings are well suited for this procedure when a well-designed device is properly implanted. The best results were obtained in men with OA, but survivorship was better for other underlying pathologies and for women after changes were made to the technique of implantation. Lifetime durability is a possible outcome for many patients despite a high level of activity. Cite this article: Bone Joint J 2018;100-B:1424–33

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