Aims. It is increasingly appreciated that coordinated regulation of angiogenesis and osteogenesis is needed for bone formation. How this regulation is achieved during peri-implant bone healing, such as osseointegration, is largely unclear. This study examined the relationship between angiogenesis and osteogenesis in a unique model of osseointegration of a mouse tibial implant by pharmacologically blocking the vascular endothelial growth factor (VEGF) pathway. Materials and Methods. An implant was inserted into the right tibia of 16-week-old female C57BL/6 mice (n = 38). Mice received anti-VEGF receptor-1 (VEGFR-1) antibody (25 mg/kg) and VEGF receptor-2 (VEGFR-2) antibody (25 mg/kg; n = 19) or an isotype control antibody (n = 19). Flow cytometric (n = 4/group) and immunofluorescent (n = 3/group) analyses were performed at two weeks post-implantation to detect the distribution and density of CD31. hi. EMCN. hi. endothelium. RNA sequencing analysis was performed using sorted CD31. hi. EMCN. hi. endothelial cells (n = 2/group). Osteoblast lineage cells expressing osterix (OSX) and osteopontin (OPN) were also detected with immunofluorescence. Mechanical pull-out testing (n = 12/group) was used at four weeks post-implantation to determine the strength of the bone-implant interface. After pull-out testing, the tissue attached to the implant surface was harvested. Whole mount immunofluorescent staining of OSX and OPN was performed to determine the amount of osteoblast lineage cells. Results. Flow cytometry revealed that anti-VEGFR treatment decreased CD31. hi. EMCN. hi. vascular endothelium in the peri-implant bone versus controls at two weeks post-implantation. This was confirmed by the decrease of CD31 and endomucin (EMCN) double-positive cells detected with immunofluorescence. In addition, treated mice had more OPN-positive cells in both peri-implant bone and tissue on the implant surface at two weeks and four weeks, respectively. More OSX-positive cells were present in peri-implant bone at two weeks. More importantly, anti-VEGFR treatment decreased the maximum load of pull-out testing compared with the control. Conclusion. VEGF pathway controls the coupling of angiogenesis and osteogenesis in orthopaedic implant osseointegration by affecting the formation of CD31. hi. EMCN. hi. endothelium. Cite this article: Bone Joint J 2019;101-B(7 Supple C):108–114

Aims . To investigate whether pre-operative functional mobility is a determinant of delayed inpatient recovery of activities (IRoA) after total knee arthroplasty (TKA) in three periods that coincided with changes in the clinical pathway. Patients and Methods. All patients (n = 682, 73% women, mean age 70 years, standard deviation 9) scheduled for TKA between 2009 and 2015 were pre-operatively screened for functional mobility by the Timed-up-and-Go test (TUG) and De Morton mobility index (DEMMI). The cut-off point for delayed IRoA was set on the day that 70% of the patients were recovered, according to the Modified Iowa Levels of Assistance Scale (mILAS) (a 5-item activity scale). In a multivariable logistic regression analysis, we added either the TUG or the DEMMI to a reference model including established determinants. Results. Both the TUG (Odds Ratio (OR) 1.10 per second, 95% confidence intervals (CI) 1.06 to 1.15) and the DEMMI (OR 0.96 per point on the 100-point scale, 95% CI 0.95 to 0.98) were statistically significant determinants of delayed IRoA in a model that also included age, BMI, ASA score and ISAR score. These associations did not depend on the time period during which the TKA took place, as assessed by tests for interaction. . Conclusion. Functional mobility, as assessed pre-operatively by the TUG and DEMMI, is an independent and stable determinant of delayed inpatient recovery of activities after TKA. Future research, focusing on improvement of pre-operative functional mobility through tailored physiotherapy intervention, should indicate whether such intervention enhances post-operative recovery among high-risk patients. Cite this article: Bone Joint J 2017;99-B:211–17

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

Aims. Approximately 10% to 20% of knee arthroplasty patients are not satisfied with the result, while a clear indication for revision surgery might not be present. Therapeutic options for these patients, who often lack adequate quadriceps strength, are limited. Therefore, the primary aim of this study was to evaluate the clinical effect of a novel rehabilitation protocol that combines low-load resistance training (LL-RT) with blood flow restriction (BFR). Methods. Between May 2022 and March 2024, we enrolled 45 dissatisfied knee arthroplasty patients who lacked any clear indication for revision to this prospective cohort study. All patients were at least six months post-surgery and had undergone conventional physiotherapy previously. The patients participated in a supervised LL-RT combined with BFR in 18 sessions. Primary assessments included the following patient-reported outcome measures (PROMs): Knee injury and Osteoarthritis Outcome Score (KOOS); Knee Society Score: satisfaction (KSSs); the EuroQol five-dimension five-level questionnaire (EQ-5D-5L); and the pain catastrophizing scale (PCS). Functionality was assessed using the six-minute walk Test (6MWT) and the 30-second chair stand test (30CST). Follow-up timepoints were at baseline, six weeks, three months, and six months after the start. Results. Six weeks of BFR with LL-RT improved all the PROMs except the sports subscale of the KOOS compared to baseline. Highest improvements after six weeks were found for quality of life (QoL) (mean 28.2 (SD 17.2) vs 19 (SD 14.7); p = 0.002), activities of daily living (mean 54.7 (SD 18.7) vs 42.9 (SD 17.3); p < 0.001), and KSSs (mean 17.1 (SD 8.8) vs 12.8 (SD 6.7); p < 0.001). PROMs improvements continued to be present at three-month and six-month follow-up compared to baseline. However, no significant differences were observed in the paired comparisons of the six-week, three-month, and six-month follow-up. The same trends are observed for the 6MWT and 30CST. Conclusion. The reported regime demonstrates improved QoL and function of dissatisfied knee arthroplasty patients. In light of this, the pathway described may provide a valuable and safe treatment option for dissatisfied knee arthroplasty patients for whom therapeutic options are limited. Cite this article: Bone Joint J 2024;106-B(12):1416–1425

Aims. In-hospital length of stay (LOS) and discharge dispositions following arthroplasty could act as surrogate measures for improvement in patient pathways, and have major cost saving implications for healthcare providers. With the ever-growing adoption of robotic technology in arthroplasty, it is imperative to evaluate its impact on LOS. The objectives of this study were to compare LOS and discharge dispositions following robotic arm-assisted total knee arthroplasty (RO TKA) and unicompartmental arthroplasty (RO UKA) versus conventional technique (CO TKA and UKA). Methods. This large-scale, single-institution study included patients of any age undergoing primary TKA (n = 1,375) or UKA (n = 337) for any cause between May 2019 and January 2023. Data extracted included patient demographics, LOS, need for post anaesthesia care unit (PACU) admission, anaesthesia type, readmission within 30 days, and discharge dispositions. Univariate and multivariate logistic regression models were also employed to identify factors and patient characteristics related to delayed discharge. Results. The median LOS in the RO TKA group was 76 hours (interquartile range (IQR) 54 to 104) versus 82.5 (IQR 58 to 127) in the CO TKA group (p < 0.001) and 54 hours (IQR 34 to 77) in the RO UKA versus 58 (IQR 35 to 81) in the CO UKA (p = 0.031). Discharge dispositions were comparable between the two groups. A higher percentage of patients undergoing CO TKA required PACU admission (8% vs 5.2%; p = 0.040). Conclusion. Our study showed that robotic arm assistance was associated with a shorter LOS in patients undergoing primary UKA and TKA, and no difference in the discharge destinations. Our results suggest that robotic arm assistance could be advantageous in partly addressing the upsurge of knee arthroplasty procedures and the concomitant healthcare burden; however, this needs to be corroborated by long-term cost-effectiveness analyses and data from randomized controlled studies. Cite this article: Bone Jt Open 2023;4(10):791–800

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. The purpose of this study was to assess total knee arthroplasty (TKA) volume and rates of early complications in morbidly obese patients over the last decade, where the introduction of quality models influencing perioperative care pathways occurred. Methods. Patients undergoing TKA between 2011 to 2018 were identified in the American College of Surgeons National Surgical Quality Improvement Program database. Patients were stratified by BMI < 40 kg/m. 2. and ≥ 40 kg/m. 2. and evaluated by the number of cases per year. The 30-day rates of any complication, wound complications, readmissions, and reoperation were assessed. Trends in these endpoints over the study period were compared between groups using odds ratios (ORs) and multivariate analyses. Results. In total, 314,695 patients underwent TKA and 46,362 (15%) had BMI ≥ 40 kg/m. 2. The prevalence of morbid obesity among TKA patients did not change greatly, ranging between 14% and 16%. Reoperation rate decreased from 1.16% to 0.96% (odds ratio (OR) 0.81 (95% confidence interval (CI) 0.66 to 0.99)) for patients with BMI < 40 kg/m. 2. , as did rates of readmission (4.46% to 2.87%; OR 0.61 (0.55 to 0.69)). Patients with BMI ≥ 40 kg/m. 2. also had fewer readmissions over the study period (4.87% to 3.34%; OR 0.64 (0.49 to 0.83)); however, the rate of reoperation did not change (1.37% to 1.41%; OR 0.99 (0.62 to 1.56)). Significant improvements were not observed for infective complications over time for either group; patients with BMI ≥ 40 kg/m. 2. had increased risk of both deep infection and wound complications compared to non-morbidly obese patients. Rate of any complication decreased for all patients. Conclusion. The proportion of TKAs in morbidly obese patients has not significantly changed over the past decade. Although readmission rates improved for all patients, reductions in reoperation in non-morbidly obese patients were not experienced by the morbidly obese, resulting in a widening of the complication gap between these cohorts. Care improvements have not lowered the differential risk of infective complications in the morbidly obese. Cite this article: Bone Joint J 2021;103-B(6 Supple A):38–44

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This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA.

Aims. The Bundled Payments for Care Improvement (BPCI) initiative has identified pathways for improving the value of care. However, patient-specific modifiable and non-modifiable risk factors may increase costs beyond the target payment. We sought to identify risk factors for exceeding our institution’s target payment, the so-called ‘bundle busters’. Patients and Methods. Using our data warehouse and Centers for Medicare and Medicaid Services (CMS) data we identified all 412 patients who underwent total joint arthroplasty and qualified for our institution’s BPCI model, between July 2015 and May 2017. Episodes where CMS payments exceeded the target payment were considered ‘busters’ (n = 123). Risk ratios (RRs) were calculated using a modified Poisson regression analysis. Results. An increased risk of exceeding the target payment was significantly associated with increasing age (adjusted RR 1.04, 95% confidence interval (CI) 1.01 to 1.06) and body mass index (adjusted RR 1.03, 95% CI 1.003 to 1.06). Eight comorbid risk factors were also identified (all p < 0.05), only two of which were considered to be potentially modifiable (diabetes with complications and preoperative anaemia). An American Society of Anesthesiologist physical status classification system (ASA) score ≥ 3 (adjusted RR 2.3, 95% CI 1.67 to 3.18) and Charlson Comorbidity Index (CCI) ≥ 3 (adjusted RR 1.94, 95% CI 1.45 to 2.60) were risk factors for bundle busting. Conclusion. Non-modifiable preoperative risk factors can increase costs and exceed the target payment. Future bundled payment models should incorporate the stratification of risk. Cite this article: Bone Joint J 2019;101-B(7 Supple C):64–69

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This Delphi study assessed the challenges of diagnosing soft-tissue knee injuries (STKIs) in acute settings among orthopaedic healthcare stakeholders.

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The aim of this study was to describe the prevalence and patterns of neuropathic pain over one year in a cohort of patients with chronic post-surgical pain at three months following total knee arthroplasty (TKA).

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The rate of day-case total knee arthroplasty (TKA) in the UK is currently approximately 0.5%. Reducing length of stay allows orthopaedic providers to improve efficiency, increase operative throughput, and tackle the rising demand for joint arthroplasty surgery and the COVID-19-related backlog. Here, we report safe delivery of day-case TKA in an NHS trust via inpatient wards with no additional resources.

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The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

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The aim of this study was to evaluate the association between chondral injury and interval from anterior cruciate ligament (ACL) tear to surgical reconstruction (ACLr).

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To investigate the impact of consecutive perioperative care transitions on in-hospital recovery of patients who had primary total knee arthroplasty (TKA) over an 11-year period.

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To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration.

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Adenosine, lidocaine, and Mg²⁺ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

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This study examined windswept deformity (WSD) of the knee, comparing prevalence and contributing factors in healthy and osteoarthritic (OA) cohorts.

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The aim of this study was to establish consensus statements on medial patellofemoral ligament (MPFL) reconstruction, anteromedialization tibial tubercle osteotomy, trochleoplasty, and rehabilitation and return to sporting activity in patients with patellar instability, using the modified Delphi process.

Aims. In Asia and the Middle-East, people often flex their knees deeply in order to perform activities of daily living. The purpose of this study was to investigate the 3D kinematics of normal knees during high-flexion activities. Our hypothesis was that the femorotibial rotation, varus-valgus angle, translations, and kinematic pathway of normal knees during high-flexion activities, varied according to activity. Materials and Methods. We investigated the in vivo kinematics of eight normal knees in four male volunteers (mean age 41.8 years; 37 to 53) using 2D and 3D registration technique, and modelled the knees with a computer aided design program. Each subject squatted, kneeled, and sat cross-legged. We evaluated the femoral rotation and varus-valgus angle relative to the tibia and anteroposterior translation of the medial and lateral side, using the transepicodylar axis as our femoral reference relative to the perpendicular projection on to the tibial plateau. This method evaluates the femur medially from what has elsewhere been described as the extension facet centre, and differs from the method classically applied. . Results. During squatting and kneeling, the knees displayed femoral external rotation. When sitting cross-legged, femurs displayed internal rotation from 10° to 100°. From 100°, femoral external rotation was observed. No significant difference in varus-valgus angle was seen between squatting and kneeling, whereas a varus position was observed from 140° when sitting cross-legged. The measure kinematic pathway using our methodology found during squatting a medial pivoting pattern from 0° to 40° and bicondylar rollback from 40° to 150°. During kneeling, a medial pivot pattern was evident. When sitting cross-legged, a lateral pivot pattern was seen from 0° to 100°, and a medial pivot pattern beyond 100°. Conclusion. The kinematics of normal knees during high flexion are variable according to activity. Nevertheless, our study was limited to a small number of male patients using a different technique to report the kinematics than previous publications. Accordingly, caution should be observed in generalizing our findings. Cite this article: Bone Joint J 2018;100-B:50–5