Aims. This study aimed to determine the expression and clinical significance of a cartilage protein, cartilage oligomeric matrix protein (COMP), in knee osteoarthritis (OA) patients. Methods. A total of 270 knee OA patients and 93 healthy controls were recruited. COMP messenger RNA (mRNA) and protein levels in serum, synovial fluid, synovial tissue, and fibroblast-like synoviocytes (FLSs) of knee OA patients were determined using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry. Results. COMP protein levels were significantly elevated in serum and synovial fluid of knee OA patients, especially those in the advanced stages of the disease. Serum COMP was significantly correlated with radiological severity as well as measures of body composition, physical performance, knee pain, and disability. Receiver operating characteristic curve analysis unveiled a diagnostic value of serum COMP as a biomarker of knee OA (41.64 ng/ml, area under the curve (AUC) = 1.00), with a sensitivity of 99.6% and a specificity of 100.0%. Further analysis uncovered that COMP mRNA expression was markedly upregulated in the inflamed synovium of knee OA, consistent with immunohistochemical staining revealing localization of COMP protein in the lining and sub-lining layers of knee OA inflamed synovium. Most notably, relative COMP mRNA expression in knee OA synovium was positively associated with its protein levels in serum and synovial fluid of knee OA patients. In human knee OA FLSs activated with tumour necrosis factor-alpha, COMP mRNA expression was considerably up-regulated in a time-dependent manner. Conclusion. All results indicate that COMP might serve as a supportive diagnostic marker for knee OA in conjunction with the standard diagnostic methods. Cite this article: Bone Joint Res 2024;13(6):261–271

Aims. Knee osteoarthritis (OA) is characterized by a chronic inflammatory process involving multiple cytokine pathways, leading to articular cartilage degeneration. Intra-articular therapies using pharmaceutical or autologous anti-inflammatory factors offer potential non-surgical treatment options. Autologous protein solution (APS) is one such product that uses the patient’s blood to produce a concentrate of cells and anti-inflammatory cytokines. This study evaluated the effect of a specific APS intra-articular injection (nSTRIDE) on patient-reported outcome measures compared to saline in moderate knee OA. Methods. A parallel, double-blinded, placebo-controlled randomized controlled trial was conducted, where patients with unilateral moderate knee OA (Kellgren-Lawrence grade 2 or 3) received either nSTRIDE or saline (placebo) injection to their symptomatic knee. The primary outcome was the difference in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score at 12 months post-intervention. Secondary outcomes included WOMAC component scores, Knee injury and Osteoarthritis Outcome Score (KOOS), and visual analogue scale (VAS) scores at all follow-up timepoints (three, six, and 12 months). Results. A total of 40 patients were analyzed (21 nSTRIDE; 19 saline) in the study. No significant difference was found between nSTRIDE and saline groups for WOMAC total score at 12 months (mean difference -10.4 (95% CI -24.4 to 3.6; p = 0.141). There were no significant differences in WOMAC or KOOS scores across all timepoints. VAS scores favoured the saline group for both rest and worst pain scales at 12 months post-injection (mean difference (worst) 12 months 21.5 (95% CI 6.2 to 36.8; p = 0.008); mean difference (rest) 12 months 17.8 (95% CI 2.2 to 33.4; p = 0.026)). There were no adverse events recorded in either study group. Conclusion. Our study demonstrates no significant differences between nSTRIDE and saline groups in KOOS and WOMAC scores over time. Notably, APS injection resulted in significantly worse pain symptoms at 12 months compared to saline injection. Cite this article: Bone Joint J 2024;106-B(9):907–915

Aims. This study aims to determine the rate of and risk factors for total knee arthroplasty (TKA) after operative management of tibial plateau fractures (TPFs) in older adults. Methods. This is a retrospective cohort study of 182 displaced TPFs in 180 patients aged ≥ 60 years, over a 12-year period with a minimum follow-up of one year. The mean age was 70.7 years (SD 7.7; 60 to 89), and 139/180 patients (77.2%) were female. Radiological assessment consisted of fracture classification; pre-existing knee osteoarthritis (OA); reduction quality; loss of reduction; and post-traumatic OA. Fracture depression was measured on CT, and the volume of defect estimated as half an oblate spheroid. Operative management, complications, reoperations, and mortality were recorded. Results. Nearly half of the fractures were Schatzker II AO B3.1 fractures (n = 85; 47%). Radiological knee OA was present at fracture in 59/182 TPFs (32.6%). Primary management was fixation in 174 (95.6%) and acute TKA in eight (4.4%). A total of 13 patients underwent late TKA (7.5%), most often within two years. By five years, 21/182 12% (95% confidence interval (CI) 6.0 to 16.7) had required TKA. Larger volume defects of greater depth on CT (median 15.9 mm vs 9.4 mm; p < 0.001) were significantly associated with TKA requirement. CT-measured joint depression of > 12.8 mm was associated with TKA requirement (area under the curve (AUC) 0.766; p = 0.001). Severe joint depression of > 15.5 mm (hazard ratio (HR) 6.15 (95% CI 2.60 to 14.55); p < 0.001) and pre-existing knee OA (HR 2.70 (95% CI 1.14 to 6.37); p = 0.024) were independently associated with TKA requirement. Where patients with severe joint depression of > 15.5 mm were managed with fixation, 11/25 ultimately required TKA. Conclusion. Overall, 12% of patients aged ≥ 60 years underwent TKA within five years of TPF. Severe joint depression and pre-existing knee arthritis were independent risk factors for both post-traumatic OA and TKA. These features should be investigated as potential indications for acute TKA in older adults with TPFs. Cite this article: Bone Joint J 2024;106-B(1):28–37

Aims. Osteoarthritis (OA) is prevalent among the elderly and incurable. Intra-articular parathyroid hormone (PTH) ameliorated OA in papain-induced and anterior cruciate ligament transection-induced OA models; therefore, we hypothesized that PTH improved OA in a preclinical age-related OA model. Methods. Guinea pigs aged between six and seven months of age were randomized into control or treatment groups. Three- or four-month-old guinea pigs served as the young control group. The knees were administered 40 μl intra-articular injections of 10 nM PTH or vehicle once a week for three months. Their endurance as determined from time on the treadmill was evaluated before kill. Their tibial plateaus were analyzed using microcalculated tomography (μCT) and histological studies. Results. PTH increased the endurance on the treadmill test, preserved glycosaminoglycans, and reduced Osteoarthritis Research Society International score and chondrocyte apoptosis rate. No difference was observed in the subchondral plate bone density or metaphyseal trabecular bone volume and bone morphogenetic 2 protein staining. Conclusion. Subchondral bone is crucial in the initiation and progression of OA. Although previous studies have shown that subcutaneous PTH alleviates knee OA by improving subchondral and metaphyseal bone mass, we demonstrated that intra-articular PTH injections improved spontaneous OA by directly affecting the cartilage rather than the subchondral or metaphyseal bone in a preclinical age-related OA model. Cite this article: Bone Joint Res 2021;10(8):514–525

Aims. The aim of this study was to estimate time to arthroplasty among patients with hip and knee osteoarthritis (OA), and to identify factors at enrolment to first-line intervention that are prognostic for progression to surgery. Methods. In this longitudinal register-based observational study, we identified 72,069 patients with hip and knee OA in the Better Management of Patients with Osteoarthritis Register (BOA), who were referred for first-line OA intervention, between May 2008 and December 2016. Patients were followed until the first primary arthroplasty surgery before 31 December 2016, stratified into a hip and a knee OA cohort. Data were analyzed with Kaplan-Meier and multivariable-adjusted Cox regression. Results. At five years, Kaplan-Meier estimates showed that 46% (95% confidence interval (CI) 44.6 to 46.9) of those with hip OA, and 20% (95% CI 19.7 to 21.0) of those with knee OA, had progressed to arthroplasty. The strongest prognostic factors were desire for surgery (hazard ratio (HR) hip 3.12 (95% CI 2.95 to 3.31), HR knee 2.72 (95% CI 2.55 to 2.90)), walking difficulties (HR hip 2.20 (95% CI 1.97 to 2.46), HR knee 1.95 (95% CI 1.73 to 2.20)), and frequent pain (HR hip 1.56 (95% CI 1.40 to 1.73), HR knee 1.77 (95% CI 1.58 to 2.00)). In hip OA, the probability of progression to surgery was lower among those with comorbidities (e.g. ≥ four conditions; HR 0.64 (95% CI 0.59 to 0.69)), with no detectable effects in the knee OA cohort. Instead, being overweight or obese increased the probability of OA progress in the knee cohort (HR 1.25 (95% CI 1.15 to 1.37)), but not among those with hip OA. Conclusion. Patients with hip OA progressed faster and to a greater extent to arthroplasty than patients with knee OA. Progression was strongly influenced by patients’ desire for surgery and by factors related to severity of OA symptoms, but factors not directly related to OA symptoms are also of importance. However, a large proportion of patients with OA do not seem to require surgery within five years, especially among those with knee OA. Cite this article: Bone Joint J 2022;104-B(7):792–800

The December 2022 Knee Roundup. 360. looks at: Effect of physical therapy versus arthroscopic partial meniscectomy: the ESCAPE trial at five years; Patellofemoral arthroplasty or total knee arthroplasty: a randomized controlled trial; Rehabilitation versus surgical reconstruction for anterior cruciate ligament injury; End-stage knee osteoarthritis in Australia: the effect of obesity; Do poor patient-reported outcome measures at six months relate to knee revision?; What is the cost of nonoperative interventions for knee osteoarthritis?

Aims. The purpose of our study was to determine whether mesenchymal stem cells (MSCs) are an effective and safe therapeutic agent for the treatment of knee osteoarthritis (OA), owing to their cartilage regeneration potential. Methods. We searched PubMed, Embase, and the Cochrane Library, with keywords including “knee osteoarthritis” and “mesenchymal stem cells”, up to June 2019. We selected randomized controlled trials (RCTs) that explored the use of MSCs to treat knee OA. The visual analogue scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), adverse events, and the whole-organ MRI score (WORMS) were used as the primary evaluation tools in the studies. Our meta-analysis included a subgroup analysis of cell dose and cell source. Results. Seven trials evaluating 256 patients were included in the meta-analysis. MSC treatment significantly improved the VAS (mean difference (MD), –13.24; 95% confidence intervals (CIs) –23.28 to –3.20, p = 0.010) and WOMAC (MD, –7.22; 95% CI –12.97 to –1.47, p = 0.010). The low-dose group with less than 30 million cells showed lower p-values for both the VAS and WOMAC. Adipose and umbilical cord–derived stem cells also had lower p-values for pain scores than those derived from bone marrow. Conclusion. Overall, MSC-based cell therapy is a relatively safe treatment that holds great potential for OA, evidenced by a positive effect on pain and knee function. Using low-dose (25 million) and adipose-derived stem cells is likely to achieve better results, but further research is needed. Cite this article: Bone Joint Res 2020;9(10):719–728

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

The June 2024 Research Roundup. 360. looks at: Do the associations of daily steps with mortality and incident cardiovascular disease differ by sedentary time levels?; Large-scale assessment of ChatGPT in benign and malignant bone tumours imaging report diagnosis and its potential for clinical applications; Long-term effects of diffuse idiopathic skeletal hyperostosis on physical function: a longitudinal analysis; Effect of intramuscular fat in the thigh muscles on muscle architecture and physical performance in the middle-aged females with knee osteoarthritis; Preoperative package of care for osteoarthritis an opportunity not to be missed?; Superiority of kinematic alignment over mechanical alignment in total knee arthroplasty during medium- to long-term follow-up: a meta-analysis and trial sequential analysis

The August 2024 Knee Roundup. 360. looks at: Calcification’s role in knee osteoarthritis: implications for surgical decision-making; Lower complication rates and shorter lengths of hospital stay with technology-assisted total knee arthroplasty; Revision surgery: the hidden burden on surgeons; Are preoperative weight loss interventions worthwhile?; Total knee arthroplasty with or without prior bariatric surgery: a systematic review and meta-analysis; Aspirin triumphs in knee arthroplasty: a decade of evidence; Efficacy of DAIR in unicompartmental knee arthroplasty: a glimpse from Oxford

The October 2023 Sports Roundup. 360. looks at: Extensor mechanism disruption in the treatment of dislocated and multiligament knee injuries; Treatment of knee osteoarthritis with injection of stem cells; Corticosteroid injection plus exercise or exercise alone as adjuvants for patients with plantar fasciitis?; Generalized joint hypermobility and a second ACL injury?; The VISA-A ((sedentary) questionnaire for Achilles tendinopathy?

Aims. Although knee osteoarthritis (OA) is diagnosed and monitored radiologically, actual full-thickness cartilage loss (FTCL) has rarely been correlated with radiological classification. This study aims to analyze which classification system correlates best with FTCL and to assess their reliability. Methods. A prospective study of 300 consecutive patients undergoing unilateral total knee arthroplasty (TKA) for OA (mean age 69 years (44 to 91; standard deviation (SD) 9.5), 178 (59%) female). Two blinded examiners independently graded preoperative radiographs using five common systems: Kellgren-Lawrence (KL); International Knee Documentation Committee (IKDC); Fairbank; Brandt; and Ahlbäck. Interobserver agreement was assessed using the intraclass correlation coefficient (ICC). Intraoperatively, anterior cruciate ligament (ACL) status and the presence of FTCL in 16 regions of interest were recorded. Radiological classification and FTCL were correlated using the Spearman correlation coefficient. Results. Knees had a mean of 6.8 regions of FTCL (SD 3.1), most common medially. The commonest patterns of FTCL were medial ± patellofemoral (143/300, 48%) and tricompartmental (89/300, 30%). ACL status was associated with pattern of FTCL (p = 0.023). All radiological classification systems demonstrated moderate ICC, but this was highest for the IKDC: whole knee 0.68 (95% confidence interval (CI) 0.60 to 0.74); medial compartment 0.84 (95% CI 0.80 to 0.87); and lateral compartment 0.79 (95% CI 0.73 to 0.83). Correlation with actual FTCL was strongest for Ahlbäck (Spearman rho 0.27 to 0.39) and KL (0.30 to 0.33) systems, although all systems demonstrated medium correlation. The Ahlbäck score was the most discriminating in severe knee OA. Osteophyte presence in the medial compartment had high positive predictive value (PPV) for FTCL, but not in the lateral compartment. Conclusion. The Ahlbäck and KL systems had the highest correlation with confirmed cartilage loss at TKA. However, the IKDC system displayed the best interobserver reliability, with favourable correlation with FTCL in medial and lateral compartments, although it was less discriminating in more severe disease. Cite this article: Bone Joint J 2020;102-B(3):301–309

Aims. Medial unicompartmental knee arthroplasty (mUKA) is an advised treatment for anteromedial knee osteoarthritis. While long-term survival after mUKA is well described, reported incidences of short-term surgical complications vary and the effect of surgical usage on complications is less established. We aimed to describe the overall occurrence and treatment of surgical complications within 90 days of mUKA, as well as occurrence in high-usage centres compared to low-usage centres. Methods. mUKAs performed in eight fast-track centres from February 2010 to June 2018 were included from the Lundbeck Foundation Centre for Fast-track Hip and Knee Replacement Database. All readmissions within 90 days of surgery underwent chart review and readmissions related to the surgical wound or the prosthesis were recorded. Centres were categorized as high-usage centres when using mUKA in ≥ 20% of annual knee arthroplasties. The occurrence of complications between high- and low-usage centres were compared using Fisher’s exact test. Results. We included 3,757 mUKAs: 2,377 mUKAs from high-usage centres and 1,380 mUKAs from low-usage centres. Surgical complications within 90 days occurred in 69 cases (1.8%), 45 (1.9%) in high-usage centres and 24 (1.7%) in low-usage centres (odds ratio (OR) 1.1 (95% confidence interval (CI) 0.65 to 1.8)). The most frequent complications were periprosthetic joint infections (PJIs) (n = 18; 0.48%), wound-related issues (n = 14; 0.37%), and periprosthetic fractures (n = 13; 0.35%). Bearing dislocations (n = 7; 0.19%) occurred primarily in procedures from high-usage centres. In high-usage centres, seven periprosthetic fractures (0.29%) occurred compared to six (0.43%) in low-usage centres (OR 0.68 (95% CI 0.20 to 2.0)). In high-usage centres, nine PJIs (0.38%) occurred compared to nine (0.65%) in low-usage centres (OR 0.58 (95% CI 0.22 to 1.6)). Conclusion. Surgical complications are rare after fast-track mUKA surgery and with no difference in overall occurrence of surgical complications between high- and low-usage centres, although the risk of some specific surgical complications may favour high-usage centres. Cite this article: Bone Jt Open 2023;4(6):457–462

The April 2024 Knee Roundup. 360. looks at: Challenging the status quo: re-evaluating the impact of obesity on unicompartmental knee arthroplasty outcomes; Timing matters: the link between ACL reconstruction delays and cartilage damage; Custom fit or off the shelf: evaluating patient outcomes in tailored versus standard knee replacements; Revolutionizing knee replacement: a comparative study on robotic-assisted and computer-navigated techniques; Pre-existing knee osteoarthritis and severe joint depression are associated with the need for total knee arthroplasty after tibial plateau fracture in patients aged over 60 years; Modern digital therapies?; A matched study on fracture rates following knee replacement surgeries;

Aims. We aimed to assess the reliability and validity of OpenPose, a posture estimation algorithm, for measurement of knee range of motion after total knee arthroplasty (TKA), in comparison to radiography and goniometry. Methods. In this prospective observational study, we analyzed 35 primary TKAs (24 patients) for knee osteoarthritis. We measured the knee angles in flexion and extension using OpenPose, radiography, and goniometry. We assessed the test-retest reliability of each method using intraclass correlation coefficient (1,1). We evaluated the ability to estimate other measurement values from the OpenPose value using linear regression analysis. We used intraclass correlation coefficients (2,1) and Bland–Altman analyses to evaluate the agreement and error between radiography and the other measurements. Results. OpenPose had excellent test-retest reliability (intraclass correlation coefficient (1,1) = 1.000). The R. 2. of all regression models indicated large correlations (0.747 to 0.927). In the flexion position, the intraclass correlation coefficients (2,1) of OpenPose indicated excellent agreement (0.953) with radiography. In the extension position, the intraclass correlation coefficients (2,1) indicated good agreement of OpenPose and radiography (0.815) and moderate agreement of goniometry with radiography (0.593). OpenPose had no systematic error in the flexion position, and a 2.3° fixed error in the extension position, compared to radiography. Conclusion. OpenPose is a reliable and valid tool for measuring flexion and extension positions after TKA. It has better accuracy than goniometry, especially in the extension position. Accurate measurement values can be obtained with low error, high reproducibility, and no contact, independent of the examiner’s skills. Cite this article: Bone Joint Res 2023;12(5):313–320

Anterior cruciate ligament (ACL) injuries are among the most common and debilitating knee injuries in professional athletes with an incidence in females up to eight-times higher than their male counterparts. ACL injuries can be career-threatening and are associated with increased risk of developing knee osteoarthritis in future life. The increased risk of ACL injury in females has been attributed to various anatomical, developmental, neuromuscular, and hormonal factors. Anatomical and hormonal factors have been identified and investigated as significant contributors including osseous anatomy, ligament laxity, and hamstring muscular recruitment. Postural stability and impact absorption are associated with the stabilizing effort and stress on the ACL during sport activity, increasing the risk of noncontact pivot injury. Female patients have smaller diameter hamstring autografts than males, which may predispose to increased risk of re-rupture following ACL reconstruction and to an increased risk of chondral and meniscal injuries. The addition of an extra-articular tenodesis can reduce the risk of failure; therefore, it should routinely be considered in young elite athletes. Prevention programs target key aspects of training including plyometrics, strengthening, balance, endurance and stability, and neuromuscular training, reducing the risk of ACL injuries in female athletes by up to 90%. Sex disparities in access to training facilities may also play an important role in the risk of ACL injuries between males and females. Similarly, football boots, pitches quality, and football size and weight should be considered and tailored around females’ characteristics. Finally, high levels of personal and sport-related stress have been shown to increase the risk of ACL injury which may be related to alterations in attention and coordination, together with increased muscular tension, and compromise the return to sport after ACL injury. Further investigations are still necessary to better understand and address the risk factors involved in ACL injuries in female athletes. Cite this article: Bone Jt Open 2024;5(2):94–100

Aims. To analyze the potential role of synovial fluid peptidase activity as a measure of disease burden and predictive biomarker of progression in knee osteoarthritis (KOA). Methods. A cross-sectional study of 39 patients (women 71.8%, men 28.2%; mean age of 72.03 years (SD 1.15) with advanced KOA (Ahlbäck grade ≥ 3 and clinical indications for arthrocentesis) recruited through the (Orthopaedic Department at the Complejo Asistencial Universitario de León, Spain (CAULE)), measuring synovial fluid levels of puromycin-sensitive aminopeptidase (PSA), neutral aminopeptidase (NAP), aminopeptidase B (APB), prolyl endopeptidase (PEP), aspartate aminopeptidase (ASP), glutamyl aminopeptidase (GLU) and pyroglutamyl aminopeptidase (PGAP). Results. Synovial fluid peptidase activity varied significantly as a function of clinical signs, with differences in levels of PEP (p = 0.020), ASP (p < 0.001), and PGAP (p = 0. 003) associated with knee locking, PEP (p = 0.006), ASP (p = 0.001), GLU (p = 0.037), and PGAP (p = 0.000) with knee failure, and PEP (p = 0.006), ASP (p = 0.001), GLU (p = 0.037), and PGAP (p < 0.001) with knee effusion. Further, patients with the greatest functional impairment had significantly higher levels of APB (p = 0.005), PEP (p = 0.005), ASP (p = 0.006), GLU (p = 0.020), and PGAP (p < 0.001) activity, though not of NAP or PSA, indicating local alterations in the renin-angiotensin system. A binary logistic regression model showed that PSA was protective (p = 0.005; Exp (B) 0.949), whereas PEP (p = 0.005) and GLU were risk factors (p = 0.012). Conclusion. These results suggest synovial fluid peptidase activity could play a role as a measure of disease burden and predictive biomarker of progression in KOA. Cite this article: Bone Joint Res 2020;9(11):789–797

Objectives. Normal sagittal spine-pelvis-lower extremity alignment is crucial in humans for maintaining an ergonomic upright standing posture, and pathogenesis in any segment leads to poor balance. The present study aimed to investigate how this sagittal alignment can be affected by severe knee osteoarthritis (KOA), and whether associated changes corresponded with symptoms of lower back pain (LBP) in this patient population. Methods. Lateral radiograph films in an upright standing position were obtained from 59 patients with severe KOA and 58 asymptomatic controls free from KOA. Sagittal alignment of the spine, pelvis, hip and proximal femur was quantified by measuring several radiographic parameters. Global balance was accessed according to the relative position of the C7 plumb line to the sacrum and femoral heads. The presence of chronic LBP was documented. Comparisons between the two groups were carried by independent samples t-tests or chi-squared test. Results. Patients with severe KOA showed significant backward femoral inclination (FI), hip flexion, forward spinal inclination, and higher prevalence of global imbalance (27.1% versus 3.4%, p < 0.001) compared with controls. In addition, patients with FI of 10° (n = 23) showed reduced lumbar lordosis and significant forward spinal inclination compared with controls, whereas those with FI > 10° (n = 36) presented with significant pelvic anteversion and hip flexion. A total of 39 patients with KOA (66.1%) suffered from LBP. There was no significant difference in sagittal alignment between KOA patients with and without LBP. Conclusions. The sagittal alignment of spine-pelvis-lower extremity axis was significantly influenced by severe KOA. The lumbar spine served as the primary source of compensation, while hip flexion and pelvic anteversion increased for further compensation. Changes in sagittal alignment may not be involved in the pathogenesis of LBP in this patient population. Cite this article: W. J. Wang, F. Liu, Y.W. Zhu, M.H. Sun, Y. Qiu, W. J. Weng. Sagittal alignment of the spine-pelvis-lower extremity axis in patients with severe knee osteoarthritis: A radiographic study. Bone Joint Res 2016;5:198–205. DOI:10.1302/2046-3758.55.2000538

Aims. The aim of this study was to evaluate the cost-effectiveness of arthroscopic partial meniscectomy versus physical therapy plus optional delayed arthroscopic partial meniscectomy in young patients aged under 45 years with traumatic meniscal tears. Methods. We conducted a multicentre, open-labelled, randomized controlled trial in patients aged 18 to 45 years, with a recent onset, traumatic, MRI-verified, isolated meniscal tear without knee osteoarthritis. Patients were randomized to arthroscopic partial meniscectomy or standardized physical therapy with an optional delayed arthroscopic partial meniscectomy after three months of follow-up. We performed a cost-utility analysis on the randomization groups to compare both treatments over a 24-month follow-up period. Cost utility was calculated as incremental costs per quality-adjusted life year (QALY) gained of arthroscopic partial meniscectomy compared to physical therapy. Calculations were performed from a healthcare system perspective and a societal perspective. Results. A total of 100 patients were included: 49 were randomized to arthroscopic partial meniscectomy and 51 to physical therapy. In the physical therapy group, 21 patients (41%) received delayed arthroscopic partial meniscectomy during follow-up. Over 24 months, patients in the arthroscopic partial meniscectomy group had a mean 0.005 QALYs lower quality of life (95% confidence interval -0.13 to 0.14). The cost-utility ratio was €-160,000/QALY from the healthcare perspective and €-223,372/QALY from the societal perspective, indicating that arthroscopic partial meniscectomy incurs additional costs without any added health benefit. Conclusion. Arthroscopic partial meniscectomy is arthroscopic partial meniscectomy is unlikely to be cost-effective in treating young patients with isolated traumatic meniscal tears compared to physical therapy as a primary health intervention. Arthroscopic partial meniscectomy leads to a similar quality of life, but higher costs, compared to physical therapy plus optional delayed arthroscopic partial meniscectomy. Cite this article: Bone Joint J 2023;105-B(11):1177–1183

Objectives. The purpose of this study was to clarify the appearance of the reparative tissue on the articular surface and to analyse the properties of the reparative tissue after hemicallotasis osteotomy (HCO) using MRI T1ρ and T2 mapping. Methods. Coronal T1ρ and T2 mapping and three-dimensional gradient-echo images were obtained from 20 subjects with medial knee osteoarthritis. We set the regions of interest (ROIs) on the full-thickness cartilage of the medial femoral condyle (MFC) and medial tibial plateau (MTP) of the knee and measured the cartilage thickness (mm) and T1ρ and T2 relaxation times (ms). Statistical analysis of time-dependent changes in the cartilage thickness and the T1ρ and T2 relaxation times was performed using one-way analysis of variance, and Scheffe’s test was employed for post hoc multiple comparison. Results. The cartilage-like repair tissue appeared on the cartilage surface of the medial compartment post-operatively, and the cartilage thickness showed a significant increase between the pre-operative and one-year post-operative time points (MFC; p = 0.003, MTP; p < 0.001). The T1ρ values of the cartilage-like repair tissue showed no difference over time, however, the T2 values showed a significant decrease between the pre-operative and one-year post-operative time points (MFC; p = 0.004, MTP; p = 0.040). Conclusion. This study clarified that the fibrocartilage-like repair tissue appeared on the articular surface of the medial compartment after HCO as evidenced by MRI T1ρ and T2 mapping. Cite this article: H. Nishioka, E. Nakamura, J. Hirose, N. Okamoto, S. Yamabe, H. Mizuta. MRI T1ρ and T2 mapping for the assessment of articular cartilage changes in patients with medial knee osteoarthritis after hemicallotasis osteotomy. Bone Joint Res 2016;5:294–300. DOI: 10.1302/2046-3758.57.BJR-2016-0057.R1

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

We investigated the association between the radiological findings and the symptoms arising from the patellofemoral joint in advanced osteoarthritis (OA) of the knee. Four radiological features, joint space narrowing, osteophyte formation, translation of the patella and focal attrition were assessed in 151 consecutive osteoarthritic knees in 107 patients undergoing total knee replacement. The symptoms which were assessed included anterior knee pain which was scored, the ability to rise from a chair and climb stairs, and quadriceps weakness.

Among the radiological features, only patellar translation and obliteration of the joint space had a statistically significant association with anterior knee pain (odds ratio (OR) 4.85; 95% confidence interval (CI) 1.83 to 12.88 and OR 11.23; 95% CI 2.44 to 51.62) respectively. Patellar translation had a statistically significant association with difficulty in rising from a chair (OR 9.06; 95% CI 1.75 to 45.11). Other radiological features, including osteophytes, joint space narrowing, and focal attrition had no significant association.

Our study indicates that the radiological findings of patellar translation and significant loss of cartilage are predictive of patellofemoral symptoms and functional limitation in advanced OA of the knee.

Aims. Knee osteoarthritis (OA) involves a variety of tissues in the joint. Gene expression profiles in different tissues are of great importance in order to understand OA. Methods. First, we obtained gene expression profiles of cartilage, synovium, subchondral bone, and meniscus from the Gene Expression Omnibus (GEO). Several datasets were standardized by merging and removing batch effects. Then, we used unsupervised clustering to divide OA into three subtypes. The gene ontology and pathway enrichment of three subtypes were analyzed. CIBERSORT was used to evaluate the infiltration of immune cells in different subtypes. Finally, OA-related genes were obtained from the Molecular Signatures Database for validation, and diagnostic markers were screened according to clinical characteristics. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) was used to verify the effectiveness of markers. Results. C1 subtype is mainly concentrated in the development of skeletal muscle organs, C2 lies in metabolic process and immune response, and C3 in pyroptosis and cell death process. Therefore, we divided OA into three subtypes: bone remodelling subtype (C1), immune metabolism subtype (C2), and cartilage degradation subtype (C3). The number of macrophage M0 and activated mast cells of C2 subtype was significantly higher than those of the other two subtypes. COL2A1 has significant differences in different subtypes. The expression of COL2A1 is related to age, and trafficking protein particle complex subunit 2 is related to the sex of OA patients. Conclusion. This study linked different tissues with gene expression profiles, revealing different molecular subtypes of patients with knee OA. The relationship between clinical characteristics and OA-related genes was also studied, which provides a new concept for the diagnosis and treatment of OA. Cite this article: Bone Joint Res 2023;12(12):702–711

Aims. Unicompartmental knee arthroplasty (UKA) is the preferred treatment for anterior medial knee osteoarthritis (OA) owing to the rapid postoperative recovery. However, the risk factors for UKA failure remain controversial. Methods. The clinical data of Oxford mobile-bearing UKAs performed between 2011 and 2017 with a minimum follow-up of five years were retrospectively analyzed. Demographic, surgical, and follow-up data were collected. The Cox proportional hazards model was used to identify the risk factors that contribute to UKA failure. Kaplan-Meier survival was used to compare the effect of the prosthesis position on UKA survival. Results. A total of 407 patients who underwent UKA were included in the study. The mean age of patients was 61.8 years, and the mean follow-up period of the patients was 91.7 months. The mean Knee Society Score (KSS) preoperatively and at the last follow-up were 64.2 and 89.7, respectively (p = 0.001). Overall, 28 patients (6.9%) with UKA underwent revision due to prosthesis loosening (16 patients), dislocation (eight patients), and persistent pain (four patients). Cox proportional hazards model analysis identified malposition of the prostheses as a high-risk factor for UKA failure (p = 0.007). Kaplan-Meier analysis revealed that the five-year survival rate of the group with malposition was 85.1%, which was significantly lower than that of the group with normal position (96.2%; p < 0.001). Conclusion. UKA constitutes an effective method for treating anteromedial knee OA, with an excellent five-year survival rate. Aseptic loosening caused by prosthesis malposition was identified as the main cause of UKA failure. Surgeons should pay close attention to prevent the potential occurrence of this problem. Cite this article: Bone Jt Open 2023;4(12):914–922

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

Aims. To compare time dependent functional improvement for patients with medial, respectively lateral knee osteoarthritis (OA) after treatment with opening wedge osteotomy relieving the pressure on the osteoarthritic part of the knee. Methods. In all, 49 patients (52 knees) with a mean age of 47 years (31 to 64) underwent high tibial osteotomies (HTO), and 24 patients with a mean age of 48 years (31 to 62) low femoral osteotomies (LFO) with opening wedge technique due to medial, respectively lateral knee OA with malalignment. All osteotomies were stabilized with a Puddu plate and bone grafting performed in the same time period (2000 to 2008). The patients were evaluated by the Knee Injury and Osteoarthritis Outcome Score (KOOS) pre-operatively and at six months, and at one, two, five, and ten years postoperatively. The knee OA was graded according to the Ahlbäck and Kellgren-Lawrence radiological scoring systems. Results. The mean angular corrections were 8.0° (4° to 12°) for the HTO and 9.6° (4° to 20°) for the LFO. Both the pre-operative KOOS and the osteoarthritic gradings were similar for the two patient groups. The five subscores of KOOS increased significantly during the postoperative period (p < 0.001 to 0.029) levelling out after one year in both groups. The KOOS subscore symptoms was significantly higher for patients with HTO than those with LFO at all follow-up times, for sport and recreation in the period one to five years, and for pain and quality of life at two to five years (p < 0.001 to 0.009). Eight HTOs (15%) and five LFOs (21%) were converted to total knee arthroplasty after mean 6.7 years (2.0 to 9.8) and 5.4 years (4.0 to 8.0) respectively. The ten-year osteotomy survival rates were 88% for the HTO and 79% for the LFO (p = 0.745). Conclusion. Patients with unicompartmental knee OA improved after a corrective opening wedge osteotomy, but four of the five subscores of KOOS were significantly higher for those with medial than those with lateral OA in most of the ten-year follow-up period. Cite this article: Bone Joint Open 2020;1-7:346–354

The April 2023 Knee Roundup. 360. looks at: Does bariatric surgery reduce complications after total knee arthroplasty?; Mid-flexion stability in total knee arthroplasties implanted with kinematic alignment: posterior-stabilized versus medial-stabilized implants; Inflammatory response in robotic-arm-assisted versus conventional jig-based total knee arthroplasty; Journey II bicruciate stabilized (JII-BCS) and GENESIS II total knee arthroplasty: the CAPAbility, blinded, randomized controlled trial; Lifetime risk of revision and patient factors; Platelet-rich plasma use for hip and knee osteoarthritis in the USA; Where have the knee revisions gone?; Tibial component rotation in total knee arthroplasty: CT-based study of 1,351 tibiae

The October 2024 Knee Roundup. 360. looks at: Managing the unexpected: treatment of intraoperative medial collateral ligament injuries; Identifying subgroups of patients that may benefit from robotic arm-assisted total knee arthroplasty: secondary analysis of data from a randomized controlled trial; Cost-effectiveness of enoxaparin versus aspirin in the prevention of venous thromboembolism after total hip or knee arthroplasty: an analysis from the CRISTAL cluster-randomized trial; Cartilage regeneration and long-term survival in medial knee osteoarthritis patients treated with high tibial osteotomy and osteochondral autologous transfer system; Treatment of chronic and complex meniscal tears with arthroscopic meniscus repair augmented with collagen matrix wrapping: failure rate and functional outcomes; Long-term outcomes of multiligament knee injuries in American football players

Aims. The aetiologies of common degenerative spine, hip, and knee pathologies are still not completely understood. Mechanical theories have suggested that those diseases are related to sagittal pelvic morphology and spinopelvic-femoral dynamics. The link between the most widely used parameter for sagittal pelvic morphology, pelvic incidence (PI), and the onset of degenerative lumbar, hip, and knee pathologies has not been studied in a large-scale setting. Methods. A total of 421 patients from the Cohort Hip and Cohort Knee (CHECK) database, a population-based observational cohort, with hip and knee complaints < 6 months, aged between 45 and 65 years old, and with lateral lumbar, hip, and knee radiographs available, were included. Sagittal spinopelvic parameters and pathologies (spondylolisthesis and degenerative disc disease (DDD)) were measured at eight-year follow-up and characteristics of hip and knee osteoarthritis (OA) at baseline and eight-year follow-up. Epidemiology of the degenerative disorders and clinical outcome scores (hip and knee pain and Western Ontario and McMaster Universities Osteoarthritis Index) were compared between low PI (< 50°), normal PI (50° to 60°), and high PI (> 60°) using generalized estimating equations. Results. Demographic details were not different between the different PI groups. L4 to L5 and L5 to S1 spondylolisthesis were more frequently present in subjects with high PI compared to low PI (L4 to L5, OR 3.717; p = 0.024 vs L5 to S1 OR 7.751; p = 0.001). L5 to S1 DDD occurred more in patients with low PI compared to high PI (OR 1.889; p = 0.010), whereas there were no differences in L4 to L5 DDD among individuals with a different PI. The incidence of hip OA was higher in participants with low PI compared to normal (OR 1.262; p = 0.414) or high PI (OR 1.337; p = 0.274), but not statistically different. The incidence of knee OA was higher in individuals with a high PI compared to low PI (OR 1.620; p = 0.034). Conclusion. High PI is a risk factor for development of spondylolisthesis and knee OA. Low pelvic incidence is related to DDD, and may be linked to OA of the hip. Level of Evidence: 1b. Cite this article: Bone Joint J 2020;102-B(9):1261–1267

The February 2023 Research Roundup. 360. looks at: Clinical and epidemiological features of scaphoid fracture nonunion; Routine sterile glove and instrument change at the time of abdominal wound closure to prevent surgical site infection (ChEETAh); Characterization of genetic risk of end-stage knee osteoarthritis treated with total knee arthroplasty; Platelet-rich plasma or autologous blood injection for plantar fasciitis; Volume and outcomes of joint arthroplasty; The hazards of absolute belief in the p-value laid bare

Aims. This study aims to determine the proportion of patients with end-stage knee osteoarthritis (OA) possibly suitable for partial (PKA) or combined partial knee arthroplasty (CPKA) according to patterns of full-thickness cartilage loss and anterior cruciate ligament (ACL) status. Methods. A cross-sectional analysis of 300 consecutive patients (mean age 69 years (SD 9.5, 44 to 91), mean body mass index (BMI) 30.6 (SD 5.5, 20 to 53), 178 female (59.3%)) undergoing total knee arthroplasty (TKA) for Kellgren-Lawrence grade ≥ 3 knee OA was conducted. The point of maximal tibial bone loss on preoperative lateral radiographs was determined as a percentage of the tibial diameter. At surgery, Lachman’s test and ACL status were recorded. The presence of full-thickness cartilage loss within 16 articular surface regions (two patella, eight femoral, six tibial) was recorded. Results. According to articular cartilage loss and ACL status, 195/293 (67%) were suitable for PKA or CPKA: medial unicompartmental knee arthroplasty (UKA) 97/293 (33%); lateral UKA 25 (9%); medial bicompartmental arthroplasty 31 (11%); lateral bicompartmental arthroplasty 12 (4%); bicondylar-UKA 23 (8%); and patellofemoral arthroplasty (PFA) seven (2%). The ACL was intact in 166 (55%), frayed in 82 (27%), disrupted in 12 (4%), and absent in 33 (11%). Lachman testing was specific (97%) but poorly sensitive (38%) for disrupted/absent ACLs. The point of maximal tibial bone loss showed good interclass correlation (ICC 0.797, 0.73 to 0.85 95% confidence interval (CI); p < 0.001) and was more posterior when the ACL was absent. Maximum tibial bone loss occurring at > 55% of the anterior to posterior distance predicted ACL absence with 93% sensitivity and 91% specificity (area under the curve 0.97 (0.94 to 0.99 95% CI; p < 0.001). Conclusion. ACL status can be reliably determined from a lateral radiograph using the location of maximal tibial bone loss. According to regions of cartilage loss and ACL status, two-thirds of patients with end-stage knee OA could potentially be treated with PKA or CPKA. Cite this article: Bone Joint J 2020;102-B(6):716–726

The February 2023 Knee Roundup. 360. looks at: Machine-learning models: are all complications predictable?; Positive cultures can be safely ignored in revision arthroplasty patients that do not meet the 2018 International Consensus Meeting Criteria; Spinal versus general anaesthesia in contemporary primary total knee arthroplasty; Preoperative pain and early arthritis are associated with poor outcomes in total knee arthroplasty; Risk factors for infection and revision surgery following patellar tendon and quadriceps tendon repairs; Supervised versus unsupervised rehabilitation following total knee arthroplasty; Kinematic alignment has similar outcomes to mechanical alignment: a systematic review and meta-analysis; Lifetime risk of revision after knee arthroplasty influenced by age, sex, and indication; Risk factors for knee osteoarthritis after traumatic knee injury

Aims. This study investigated the effects of transcatheter arterial embolization (TAE) on pain, function, and quality of life in people with early-stage symptomatic knee osteoarthritis (OA) compared to a sham procedure. Methods. A total of 59 participants with symptomatic Kellgren-Lawrence grade 2 knee OA were randomly allocated to TAE or a sham procedure. The intervention group underwent TAE of one or more genicular arteries. The control group received a blinded sham procedure. The primary outcome was knee pain at 12 months according to the Knee injury and Osteoarthritis Outcome Score (KOOS) pain scale. Secondary outcomes included self-reported function and quality of life (KOOS, EuroQol five-dimension five-level questionnaire (EQ-5D-5L)), self-reported Global Change, six-minute walk test, 30-second chair stand test, and adverse events. Subgroup analyses compared participants who received complete embolization of all genicular arteries (as distinct from embolization of some arteries) (n = 17) with the control group (n = 29) for KOOS and Global Change scores at 12 months. Continuous variables were analyzed with quantile regression, adjusting for baseline scores. Dichotomized variables were analyzed with chi-squared tests. Results. Overall, 58 participants provided questionnaire data at 12 months. No significant differences were found for the primary and secondary outcomes, with both groups improving following the procedure. At 12 months, KOOS pain scores improved by 41.3% and 29.4% in the intervention and control groups, respectively. No adverse events occurred. Subgroup analysis indicated that the complete embolization group had significantly better KOOS Sports and Recreation, KOOS Quality of Life, and Global Change scores than the control group; 76.5% of participants who received complete embolization reporting being moderately or much better compared to 37.9% of the control group. Conclusion. TAE might produce benefits above placebo, but only when complete embolization of all genicular arteries is performed. Further comparative studies are required before definitive conclusions regarding the effectiveness of TAE can be made. Level of evidence: I. Cite this article: Bone Jt Open 2023;4(3):158–167

Aims. The mid-term results of kinematic alignment (KA) for total knee arthroplasty (TKA) using image derived instrumentation (IDI) have not been reported in detail, and questions remain regarding ligamentous stability and revisions. This paper aims to address the following: 1) what is the distribution of alignment of KA TKAs using IDI; 2) is a TKA alignment category associated with increased risk of failure or poor patient outcomes; 3) does extending limb alignment lead to changes in soft-tissue laxity; and 4) what is the five-year survivorship and outcomes of KA TKA using IDI?. Methods. A prospective, multicentre, trial enrolled 100 patients undergoing KA TKA using IDI, with follow-up to five years. Alignment measures were conducted pre- and postoperatively to assess constitutional alignment and final implant position. Patient-reported outcome measures (PROMs) of pain and function were also included. The Australian Orthopaedic Association National Joint Arthroplasty Registry was used to assess survivorship. Results. The postoperative HKA distribution varied from 9° varus to 11° valgus. All PROMs showed statistical improvements at one year (p < 0.001), with further improvements at five years for Knee Osteoarthritis Outcome Score symptoms (p = 0.041) and Forgotten Joint Score (p = 0.011). Correlation analysis showed no difference (p = 0.610) between the hip-knee-ankle and joint line congruence angle at one and five years. Sub-group analysis showed no difference in PROMs for patients placed within 3° of neutral compared to those placed > 3°. There were no revisions for tibial loosening; however, there were reports of a higher incidence of poor patella tracking and patellofemoral stiffness. Conclusion. PROMs were not impacted by postoperative alignment category. Ligamentous stability was maintained at five years with joint line obliquity. There were no revisions for tibial loosening despite a significant portion of tibiae placed in varus; however, KA executed with IDI resulted in a higher than anticipated rate of patella complications. Cite this article: Bone Jt Open 2022;3(8):656–665

Aims. Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA). Methods. Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers. Results. The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined media. MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC and suppressed MIA-induced synovitis, accompanied by the recovery of cartilage matrix. Pharmacological inhibitors of PEDF receptor (PEDFR) and signal transducer and activator of transcription 3 (STAT3) signalling substantially blocked the chondrogenic promoting activity of 29-mer on the cultured BM-MSCs and injured AC. Conclusion. The 29-mer/HA formulation effectively induces chondrocyte regeneration and formation of cartilage matrix in the damaged AC. Cite this article: Bone Joint Res 2024;13(4):137–148

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. Platelet-rich plasma (PRP) intra-articular injections may provide a simple and minimally invasive treatment for early-stage knee osteoarthritis (OA). This has led to an increase in its adoption as a treatment for knee OA, although there is uncertainty about its efficacy and benefit. We hypothesized that patients with early-stage symptomatic knee OA who receive multiple PRP injections will have better clinical outcomes than those receiving single PRP or placebo injections. Methods. A double-blinded, randomized placebo-controlled trial was performed with three groups receiving either placebo injections (Normal Saline), one PRP injection followed by two placebo injections, or three PRP injections. Each injection was given one week apart. Outcomes were prospectively collected prior to intervention and then at six weeks, three months, six months, and 12 months post-intervention. Primary outcome measures were Knee Injury and Osteoarthritis Outcome Score (KOOS) and EuroQol five-dimension five-level index (EQ-5D-5L). Secondary outcomes included visual analogue scale for pain and patient subjective assessment of the injections. Results. A total of 102 patients were recruited. The follow-up period was 12 months, at intervals of six weeks, 12 weeks, six months, and 12 months. KOOS-Total significantly improved in all groups at these time intervals compared to pre-injection. There was an improvement in EQ-5D-5L index scores in saline and single injection groups, but not in the multiple injection group. Comparison of treatment groups showed no additional beneficial effect of single or multiple PRP injections above that displayed in the saline injection group. Subjective patient satisfaction and recommendation of treatment received demonstrated a similar pattern in all the groups. There was no indication of superiority of either single or multiple PRP injections compared to saline injections. Conclusion. There is no evidence that single or multiple PRP had any additional beneficial effect compared to saline injection up to 12 months, follow-up after treatment of early stage symptomatic OA of the knee. Cite this article: Bone Joint J 2022;104-B(6):663–671

Aims. To determine the relationship between articular cartilage status and clinical outcomes after medial opening-wedge high tibial osteotomy (MOHTO) for medial compartmental knee osteoarthritis at intermediate follow-up. Methods. We reviewed 155 patients (155 knees) who underwent MOHTO from January 2008 to December 2016 followed by second-look arthroscopy with a mean 5.3-year follow-up (2.0 to 11.7). Arthroscopic findings were assessed according to the International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) grading system. Patients were divided into two groups based on the presence of normal or nearly normal quality cartilage in the medial femoral condyle: good (second-look arthroscopic) status (ICRS grade I or II; n = 70), and poor (second-look arthroscopic) status (ICRS grade III or IV; n = 85) groups at the time of second-look arthroscopy. Clinical outcomes were assessed using the International Knee Documentation Committee (IKDC) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 36-Item Short Form survey. Results. Significant improvements in all clinical outcome categories were found between the preoperative and second-look arthroscopic assessments in both groups (p < 0.001). At the latest follow-up, the mean IKDC and WOMAC scores in the good status group further improved compared with those at the time of second-look arthroscopic surgery (p < 0.001), which was not shown in the poor status group. The mean IKDC (good status, 72.8 (SD 12.5); poor status, 64.7 (SD 12.1); p = 0.002) and mean WOMAC scores (good status, 15.7 (SD 10.8); poor status, 21.8 (SD 13.6); p = 0.004) significantly differed between both groups at the latest follow-up. Moreover, significant correlations were observed between ICRS CRA grades and IKDC scores (negative correlation; p < 0.001) and WOMAC scores (positive correlation; p < 0.001) at the latest follow-up. Good cartilage status was found more frequently in knees with the desired range of 2° to 6° valgus correction than in those with corrections outside this range (p = 0.019). Conclusion. Second-look arthroscopic cartilage status correlated with clinical outcomes after MOHTO at intermediate-term follow-up, despite the relatively small clinical differences between groups. Cite this article: Bone Joint J 2021;103-B(11):1686–1694

Aims. To explore the clinical relevance of joint space width (JSW) narrowing on standardized-flexion (SF) radiographs in the assessment of cartilage degeneration in specific subregions seen on MRI sequences in knee osteoarthritis (OA) with neutral, valgus, and varus alignments, and potential planning of partial knee arthroplasty. Methods. We retrospectively reviewed 639 subjects, aged 45 to 79 years, in the Osteoarthritis Initiative (OAI) study, who had symptomatic knees with Kellgren and Lawrence grade 2 to 4. Knees were categorized as neutral, valgus, and varus knees by measuring hip-knee-angles on hip-knee-ankle radiographs. Femorotibial JSW was measured on posteroanterior SF radiographs using a special software. The femorotibial compartment was divided into 16 subregions, and MR-tomographic measurements of cartilage volume, thickness, and subchondral bone area were documented. Linear regression with adjustment for age, sex, body mass index, and Kellgren and Lawrence grade was used. Results. We studied 345 neutral, 87 valgus, and 207 varus knees. Radiological JSW narrowing was significantly (p < 0.01) associated with cartilage volume and thickness in medial femorotibial compartment in neutral (r = 0.78, odds ratio (OR) 2.33) and varus knees (r = 0.86, OR 1.92), and in lateral tibial subregions in valgus knees (r = 0.87, OR 3.71). A significant negative correlation was found between JSW narrowing and area of subchondral bone in external lateral tibial subregion in valgus knees (r = −0.65, p < 0.01) and in external medial tibial subregion in varus knees (r = −0.77, p < 0.01). No statistically significant correlation was found in anterior and posterior subregions. Conclusion. SF radiographs can be potentially used for initial detection of cartilage degeneration as assessed by MRI in medial and lateral but not in anterior or posterior subregions. Cite this article: Bone Joint Res 2021;10(3):173–187

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

Aims. To assess how the cost-effectiveness of total hip arthroplasty (THA) and total knee arthroplasty (TKA) varies with age, sex, and preoperative Oxford Hip or Knee Score (OHS/OKS); and to identify the patient groups for whom THA/TKA is cost-effective. Methods. We conducted a cost-effectiveness analysis using a Markov model from a United Kingdom NHS perspective, informed by published analyses of patient-level data. We assessed the cost-effectiveness of THA and TKA in adults with hip or knee osteoarthritis compared with having no arthroplasty surgery during the ten-year time horizon. Results. THA and TKA cost < £7,000 per quality-adjusted life-year (QALY) gained at all preoperative scores below the absolute referral thresholds calculated previously (40 for OHS and 41 for OKS). Furthermore, THA cost < £20,000/QALY for patients with OHS of ≤ 45, while TKA was cost-effective for patients with OKS of ≤ 43, since the small improvements in quality of life outweighed the cost of surgery and any subsequent revisions. Probabilistic and one-way sensitivity analyses demonstrated that there is little uncertainty around the conclusions. Conclusion. If society is willing to pay £20,000 per QALY gained, THA and TKA are cost-effective for nearly all patients who currently undergo surgery, including all patients at and above our calculated absolute referral thresholds. Cite this article: Bone Joint J 2020;102-B(7):950–958

Aims. Anterior cruciate ligament (ACL) and multiligament knee (MLK) injuries increase the risk of development of knee osteoarthritis and eventual need for total knee arthroplasty (TKA). There are limited data regarding implant use and outcomes in these patients. The aim of this study was to compare the use of constrained implants and outcomes among patients undergoing TKA with a history of prior knee ligament reconstruction (PKLR) versus a matched cohort of patients undergoing TKA with no history of PKLR. Patients and Methods. Patients with a history of ACL or MLK reconstruction who underwent TKA between 2007 and 2017 were identified in a single-institution registry. There were 223 patients who met inclusion criteria (188 ACL reconstruction patients, 35 MLK reconstruction patients). A matched cohort, also of 223 patients, was identified based on patient age, body mass index (BMI), sex, and year of surgery. There were 144 male patients and 79 female patients in both cohorts. Mean age at the time of TKA was 57.2 years (31 to 88). Mean BMI was 29.7 kg/m. 2. (19.5 to 55.7). Results. There was a significantly higher use of constrained implants among patients with PKLR (76 of 223, 34.1%) compared with the control group (40 of 223, 17.9%; p < 0.001). Subgroup analysis showed a higher use of constrained implants among patients with prior MLK reconstruction (21 of 35, 60.0%) compared with ACL reconstruction (55 of 188, 29.3%; p < 0.001). Removal of hardware was performed in 69.5% of patients with PKLR. Mean operative time (p < 0.001) and tourniquet time (p < 0.001) were longer in patients with PKLR compared with controls. There were no significant differences in rates of deep vein thrombosis, pulmonary embolism, infection, transfusion, postoperative knee range of movement (ROM), or need for revision surgery. There was no significant difference in preoperative or postoperative Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS, JR) scores between groups. Conclusion. Results of this study suggest a history of PKLR results in increased use of constrained implants but no difference in postoperative knee ROM, patient-reported outcomes, or incidence of revision surgery. Cite this article: Bone Joint J 2019;101-B(7 Supple C):77–83

Aims

Total knee arthroplasty (TKA) may provoke ankle symptoms. The aim of this study was to validate the impact of the preoperative mechanical tibiofemoral angle (mTFA), the talar tilt (TT) on ankle symptoms after TKA, and assess changes in the range of motion (ROM) of the subtalar joint, foot posture, and ankle laxity.

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To explore key stakeholder views around feasibility and acceptability of trials seeking to prevent post-traumatic osteoarthritis (PTOA) following knee injury, and provide guidance for next steps in PTOA trial design.

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This study investigates whether primary knee arthroplasty (KA) restores health-related quality of life (HRQoL) to levels expected in the general population.

Aims. Osteoarthritis (OA) is a disabling joint disorder and mechanical loading is an important pathogenesis. This study aims to investigate the benefits of less mechanical loading created by intermittent tail suspension for knee OA. Methods. A post-traumatic OA model was established in 20 rats (12 weeks old, male). Ten rats were treated with less mechanical loading through intermittent tail suspension, while another ten rats were treated with normal mechanical loading. Cartilage damage was determined by gross appearance, Safranin O/Fast Green staining, and immunohistochemistry examinations. Subchondral bone changes were analyzed by micro-CT and tartrate-resistant acid phosphatase (TRAP) staining, and serum inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA). Results. Our radiographs showed that joint space was significantly enlarged in rats with less mechanical loading. Moreover, cartilage destruction was attenuated in the less mechanical loading group with lower histological damage scores, and lower expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, matrix metalloproteinase (MMP)-3, and MMP-13. In addition, subchondral bone abnormal changes were ameliorated in OA rats with less mechanical loading, as reduced bone mineral density (BMD), bone volume/tissue volume (BV/TV), and number of osteophytes and osteoclasts in the subchondral bone were observed. Finally, the level of serum inflammatory cytokines was significantly downregulated in the less mechanical loading group compared with the normal mechanical loading group, as well as the expression of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), caspase-1, and interleukin 1β (IL-1β) in the cartilage. Conclusion. Less mechanical loading alleviates cartilage destruction, subchondral bone changes, and secondary inflammation in OA joints. This study provides fundamental insights into the benefit of non-weight loading rest for patients with OA. Cite this article: Bone Joint Res 2020;9(10):731–741

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The preventive effects of bisphosphonates on articular cartilage in non-arthritic joints are unclear. This study aimed to investigate the effects of oral bisphosphonates on the rate of joint space narrowing in the non-arthritic hip.

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Machine learning (ML), a branch of artificial intelligence that uses algorithms to learn from data and make predictions, offers a pathway towards more personalized and tailored surgical treatments. This approach is particularly relevant to prevalent joint diseases such as osteoarthritis (OA). In contrast to end-stage disease, where joint arthroplasty provides excellent results, early stages of OA currently lack effective therapies to halt or reverse progression. Accurate prediction of OA progression is crucial if timely interventions are to be developed, to enhance patient care and optimize the design of clinical trials.

Objectives. Metabolic syndrome and low-grade systemic inflammation are associated with knee osteoarthritis (OA), but the relationships between these factors and OA in other synovial joints are unclear. The aim of this study was to determine if a high-fat/high-sucrose (HFS) diet results in OA-like joint damage in the shoulders, knees, and hips of rats after induction of obesity, and to identify potential joint-specific risks for OA-like changes. Methods. A total of 16 male Sprague-Dawley rats were allocated to either the diet-induced obesity group (DIO, 40% fat, 45% sucrose, n = 9) or a chow control diet (n = 7) for 12 weeks. At sacrifice, histological assessments of the shoulder, hip, and knee joints were performed. Serum inflammatory mediators and body composition were also evaluated. The total Mankin score for each animal was assessed by adding together the individual Modified Mankin scores across all three joints. Linear regression modelling was conducted to evaluate predictive relationships between serum mediators and total joint damage. Results. The HFS diet, in the absence of trauma, resulted in increased joint damage in the shoulder and knee joints of rats. Hip joint damage, however, was not significantly affected by DIO, consistent with findings in human studies. The total Mankin score was increased in DIO animals compared with the chow group, and was associated with percentage of body fat. Positive significant predictive relationships for total Mankin score were found between body fat and two serum mediators (interleukin 1 alpha (IL-1α) and vascular endothelial growth factor (VEGF)). Conclusion. Systemic inflammatory alterations from DIO in this model system may result in a higher risk for development of knee, shoulder, and multi-joint damage with a HFS diet. Cite this article: K. H. Collins, D. A. Hart, R. A. Seerattan, R. A. Reimer, W. Herzog. High-fat/high-sucrose diet-induced obesity results in joint-specific development of osteoarthritis-like degeneration in a rat model. Bone Joint Res 2018;7:274–281. DOI: 10.1302/2046-3758.74.BJR-2017-0201.R2