Many different designs of total hip arthroplasty (THA) with varying performance and cost are available. The identification of those which are the most cost-effective could allow significant cost-savings. We used an established Markov model to examine the cost effectiveness of five frequently used categories of THA which differed according to bearing surface and mode of fixation, using data from the National Joint Registry for England and Wales. Kaplan–Meier analyses of rates of revision for men and women were modelled with parametric distributions. Costs of devices were provided by the NHS Supply Chain and associated costs were taken from existing studies. Lifetime costs, lifetime quality-adjusted-life-years (QALYs) and the probability of a device being cost effective at a willingness to pay £20 000/QALY were included in the models.

The differences in QALYs between different categories of implant were extremely small (<  0.0039 QALYs for men or women over the patient’s lifetime) and differences in cost were also marginal (£2500 to £3000 in the same time period). As a result, the probability of any particular device being the most cost effective was very sensitive to small, plausible changes in quality of life estimates and cost.

Our results suggest that available evidence does not support recommending a particular device on cost effectiveness grounds alone. We would recommend that the choice of prosthesis should be determined by the rate of revision, local costs and the preferences of the surgeon and patient.

Cite this article: Bone Joint J 2015;97-B:449–57.

Aims

The purpose of this study was to compare the clinical and radiographic outcomes of total ankle arthroplasty (TAA) in patients with pre-operatively moderate and severe arthritic varus ankles to those achieved for patients with neutral ankles.

Aims. Osteoarthritis (OA) is a prevalent joint disorder with inflammatory response and cartilage deterioration as its main features. Dihydrocaffeic acid (DHCA), a bioactive component extracted from natural plant (gynura bicolor), has demonstrated anti-inflammatory properties in various diseases. We aimed to explore the chondroprotective effect of DHCA on OA and its potential mechanism. Methods. In vitro, interleukin-1 beta (IL-1β) was used to establish the mice OA chondrocytes. Cell counting kit-8 evaluated chondrocyte viability. Western blotting analyzed the expression levels of collagen II, aggrecan, SOX9, inducible nitric oxide synthase (iNOS), IL-6, matrix metalloproteinases (MMPs: MMP1, MMP3, and MMP13), and signalling molecules associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Immunofluorescence analysis assessed the expression of aggrecan, collagen II, MMP13, and p-P65. In vivo, a destabilized medial meniscus (DMM) surgery was used to induce mice OA knee joints. After injection of DHCA or a vehicle into the injured joints, histological staining gauged the severity of cartilage damage. Results. DHCA prevented iNOS and IL-6 from being upregulated by IL-1β. Moreover, the IL-1β-induced upregulation of MMPs could be inhibited by DHCA. Additionally, the administration of DHCA counteracted IL-1β-induced downregulation of aggrecan, collagen II, and SOX9. DHCA protected articular cartilage by blocking the NF-κB and MAPK pathways. Furthermore, DHCA mitigated the destruction of articular cartilage in vivo. Conclusion. We present evidence that DHCA alleviates inflammation and cartilage degradation in OA chondrocytes via suppressing the NF-κB and MAPK pathways, indicating that DHCA may be a potential agent for OA treatment. Cite this article: Bone Joint Res 2023;12(4):259–273

Aims. Osteoarthritis (OA) is the most common chronic pathema of human joints. The pathogenesis is complex, involving physiological and mechanical factors. In previous studies, we found that ferroptosis is intimately related to OA, while the role of Sat1 in chondrocyte ferroptosis and OA, as well as the underlying mechanism, remains unclear. Methods. In this study, interleukin-1β (IL-1β) was used to simulate inflammation and Erastin was used to simulate ferroptosis in vitro. We used small interfering RNA (siRNA) to knock down the spermidine/spermine N1-acetyltransferase 1 (Sat1) and arachidonate 15-lipoxygenase (Alox15), and examined damage-associated events including inflammation, ferroptosis, and oxidative stress of chondrocytes. In addition, a destabilization of the medial meniscus (DMM) mouse model of OA induced by surgery was established to investigate the role of Sat1 inhibition in OA progression. Results. The results showed that inhibition of Sat1 expression can reduce inflammation, ferroptosis changes, reactive oxygen species (ROS) level, and lipid-ROS accumulation induced by IL-1β and Erastin. Knockdown of Sat1 promotes nuclear factor-E2-related factor 2 (Nrf2) signalling. Additionally, knockdown Alox15 can alleviate the inflammation-related protein expression induced by IL-1β and ferroptosis-related protein expression induced by Erastin. Furthermore, knockdown Nrf2 can reverse these protein expression alterations. Finally, intra-articular injection of diminazene aceturate (DA), an inhibitor of Sat1, enhanced type II collagen (collagen II) and increased Sat1 and Alox15 expression. Conclusion. Our results demonstrate that inhibition of Sat1 could alleviate chondrocyte ferroptosis and inflammation by downregulating Alox15 activating the Nrf2 system, and delaying the progression of OA. These findings suggest that Sat1 provides a new approach for studying and treating OA. Cite this article: Bone Joint Res 2024;13(3):110–123

Aims. After a few passages of in vitro culture, primary human articular chondrocytes undergo senescence and loss of their phenotype. Most of the available chondrocyte cell lines have been obtained from cartilage tissues different from diarthrodial joints, and their utility for osteoarthritis (OA) research is reduced. Thus, the goal of this research was the development of immortalized chondrocyte cell lines proceeded from the articular cartilage of patients with and without OA. Methods. Using telomerase reverse transcriptase (hTERT) and SV40 large T antigen (SV40LT), we transduced primary OA articular chondrocytes. Proliferative capacity, degree of senescence, and chondrocyte surface antigen expression in transduced chondrocytes were evaluated. In addition, the capacity of transduced chondrocytes to synthesize a tissue similar to cartilage and to respond to interleukin (IL)-1β was assessed. Results. Coexpression of both transgenes (SV40 and hTERT) were observed in the nuclei of transduced chondrocytes. Generated chondrocyte cell lines showed a high proliferation capacity and less than 2% of senescent cells. These cell lines were able to form 3D aggregates analogous to those generated by primary articular chondrocytes, but were unsuccessful in synthesizing cartilage-like tissue when seeded on type I collagen sponges. However, generated chondrocyte cell lines maintained the potential to respond to IL-1β stimulation. Conclusion. Through SV40LT and hTERT transduction, we successfully immortalized chondrocytes. These immortalized chondrocytes were able to overcome senescence in vitro, but were incapable of synthesizing cartilage-like tissue under the experimental conditions. Nonetheless, these chondrocyte cell lines could be advantageous for OA investigation since, similarly to primary articular chondrocytes, they showed capacity to upregulate inflammatory mediators in response to the IL-1β cytokine. Cite this article: Bone Joint Res 2023;12(1):46–57

The aim of this study was to examine the loading of the other joints of the lower limb in patients with unilateral osteoarthritis (OA) of the knee. We recruited 20 patients with no other symptoms or deformity in the lower limbs from a consecutive cohort of patients awaiting knee replacement. Gait analysis and electromyographic recordings were performed to determine moments at both knees and hips, and contraction patterns in the medial and lateral quadriceps and hamstrings bilaterally. The speed of gait was reduced in the group with OA compared with the controls, but there were only minor differences in stance times between the limbs. Patients with OA of the knee had significant increases in adduction moment impulse at both knees and the contralateral hip (adjusted p-values: affected knee: p < 0.01, unaffected knee p = 0.048, contralateral hip p = 0.03), and significantly increased muscular co-contraction bilaterally compared with controls (all comparisons for co-contraction, p < 0.01).

The other major weight-bearing joints are at risk from abnormal biomechanics in patients with unilateral OA of the knee.

Cite this article: Bone Joint J 2013;95-B:348–53.

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

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

Aims. The prevalence of osteoarthritis (OA) associated with instability of the shoulder ranges between 4% and 60%. Articular cartilage is, however, routinely assessed in these patients using radiographs or scans (2D or 3D), with little opportunity to record early signs of cartilage damage. The aim of this study was to assess the prevalence and localization of chondral lesions and synovial damage in patients undergoing arthroscopic surgery for instablility of the shoulder, in order to classify them and to identify risk factors for the development of glenohumeral OA. Methods. A total of 140 shoulders in 140 patients with a mean age of 28.5 years (15 to 55), who underwent arthroscopic treatment for recurrent glenohumeral instability, were included. The prevalence and distribution of chondral lesions and synovial damage were analyzed and graded into stages according to the division of the humeral head and glenoid into quadrants. The following factors that might affect the prevalence and severity of chondral damage were recorded: sex, dominance, age, age at the time of the first dislocation, number of dislocations, time between the first dislocation and surgery, preoperative sporting activity, Beighton score, type of instability, and joint laxity. Results. A total of 133 patients (95%) had synovial or chondral lesions. At the time of surgery, shoulders were graded as having mild, moderate, and severe OA in 55 (39.2%), 72 (51.4%), and six (4.2%) patients, respectively. A Hill-Sachs lesion and fibrillation affecting the anteroinferior glenoid cartilage were the most common findings. There was a significant positive correlation between the the severity of the development of glenohumeral OA and the patient’s age, their age at the time of the first dislocation, and the number of dislocations (p = 0.004, p = 0.011, and p = 0.031, respectively). Conclusion. Synovial inflammation and chondral damage associated with instability of the shoulder are more prevalent than previously reported. The classification using quadrants gives surgeons more information about the chondral damage, and could explain the pattern of development of glenohumeral OA after stabilization of the shoulder. As the number of dislocations showed a positive correlation with the development of OA, this might be an argument for early stabilization. Cite this article: Bone Joint J 2024;106-B(10):1125–1132

Aims. For the increasing number of working-age patients undergoing total hip or total knee arthroplasty (THA/TKA), return to work (RTW) after surgery is crucial. We investigated the association between occupational class and time to RTW after THA or TKA. Methods. Data from the prospective multicentre Longitudinal Leiden Orthopaedics Outcomes of Osteoarthritis Study were used. Questionnaires were completed preoperatively and six and 12 months postoperatively. Time to RTW was defined as days from surgery until RTW (full or partial). Occupational class was preoperatively assessed and categorized into four categories according to the International Standard Classification of Occupations 2008 (blue-/white-collar, high-/low-skilled). Cox regression analyses were conducted separately for THA and TKA patients. Low-skilled blue-collar work was used as the reference category. Results. A total of 360 THA and 276 TKA patients, preoperatively employed, were included. Patients were mainly high-skilled (THA 57%; TKA 41%) or low-skilled (THA 24%; TKA 38%) white-collar workers. Six months post-THA, RTW rates were 78% of low-skilled blue-collar workers compared to 83% to 86% within other occupational classes, increasing after 12 months to 87% to 90% in all occupational classes. Six months post-TKA, RTW rates were 58% of low-skilled and 64% of high-skilled blue-collar workers compared to 80% to 89% of white-collar workers, and after 12 months 79% of low-skilled blue-collar workers compared to 87% to 92% within other occupational classes. High-skilled white-collar workers (THA: hazard ratio (HR) 2.12 (95% confidence interval (CI) 1.32 to 3.40); TKA: HR 2.31 (95% CI 1.34 to 4.00)) and low-skilled white-collar workers (TKA: HR 1.82 (95% CI 1.04 to 3.18)) had a higher hazard to RTW within six months postoperatively. Conclusion. Clear differences existed in time to RTW among both THA and TKA patients in each of the groups studied. These findings may help guide tailored patient-specific information during preoperative consultation and advice postoperatively, as well as to create awareness among workers and their employers. Cite this article: Bone Joint J 2023;105-B(9):977–984

Aims. Pelvic tilt is believed to affect the symptomology of osteoarthritis (OA) of the hip by alterations in joint movement, dysplasia of the hip by modification of acetabular cover, and femoroacetabular impingement by influencing the impingement-free range of motion. While the apparent role of pelvic tilt in hip pathology has been reported, the exact effects of many forms of treatment on pelvic tilt are unknown. The primary aim of this study was to investigate the effects of surgery on pelvic tilt in these three groups of patients. Methods. The demographic, radiological, and outcome data for all patients operated on by the senior author between October 2016 and January 2020 were identified from a prospective registry, and all those who underwent surgery with a primary diagnosis of OA, dysplasia, or femoroacetabular impingement were considered for inclusion. Pelvic tilt was assessed on anteroposterior (AP) standing radiographs using the pre- and postoperative pubic symphysis to sacroiliac joint (PS-SI) distance, and the outcomes were assessed with the Hip Outcome Score (HOS), International Hip Outcome Tool (iHOT-12), and Harris Hip Score (HHS). Results. The linear regression model revealed a significant negative predictive association between the standing pre- and postoperative PS-SI distances for all three groups of patients (all p < 0.001). There was a significant improvement in all three outcome measures between the pre- and postoperative values (p < 0.05). Conclusion. There is a statistically significant decrease in pelvic tilt after surgery in patients with OA of the hip, dysplasia, and femoroacetabular impingement. These results confirm that surgery significantly alters the pelvic orientation. Pelvic tilt significantly decreased after total hip arthroplasty, periacetabular osteotomy, and arthroscopy/surgical hip dislocation. The impact of surgery on pelvic tilt should be considered within the therapeutic plan in order to optimize pelvic orientation in these patients. Cite this article: Bone Joint J 2022;104-B(9):1025–1031

We compared the five- to seven-year clinical and radiological results of the metal-on-metal Birmingham hip resurfacing with a hybrid total hip arthroplasty in two groups of 54 hips, matched for gender, age, body mass index and activity level.

Function was excellent in both groups, as measured by the Oxford hip score, but the Birmingham hip resurfacings had higher University of California at Los Angeles activity scores and better EuroQol quality of life scores. The total hip arthroplasties had a revision or intention-to-revise rate of 8%, and the Birmingham hip resurfacings of 6%. Both groups demonstrated impending failure on surrogate end-points. Of the total hip arthroplasties, 12% had polyethylene wear and osteolysis under observation, and 8% of Birmingham hip resurfacings showed migration of the femoral component. Polyethylene wear was present in 48% of the hybrid hips without osteolysis. Of the femoral components in the Birmingham hip resurfacing group which had not migrated, 66% had radiological changes of unknown significance.

Aims. The aim of this study was to report the meaningful values of the EuroQol five-dimension three-level questionnaire (EQ-5D-3L) and EuroQol visual analogue scale (EQ-VAS) in patients undergoing primary knee arthroplasty (KA). Methods. This is a retrospective study of patients undergoing primary KA for osteoarthritis in a university teaching hospital (Royal Infirmary of Edinburgh) (1 January 2013 to 31 December 2019). Pre- and postoperative (one-year) data were prospectively collected for 3,181 patients (median age 69.9 years (interquartile range (IQR) 64.2 to 76.1); females, n = 1,745 (54.9%); median BMI 30.1 kg/m. 2. (IQR 26.6 to 34.2)). The reliability of the EQ-5D-3L was measured using Cronbach’s alpha. Responsiveness was determined by calculating the anchor-based minimal clinically important difference (MCID), the minimal important change (MIC) (cohort and individual), the patient-acceptable symptom state (PASS) predictive of satisfaction, and the minimal detectable change at 90% confidence intervals (MDC-90). Results. The EQ-5D-3L demonstrated good internal consistency with an overall Cronbach alpha of 0.75 (preoperative) and 0.88 (postoperative), respectively. The MCID for the Index score was 0.085 (95% confidence interval (CI) 0.042 to 0.127) and EQ-VAS was 6.41 (95% CI 3.497 to 9.323). The MIC. COHORT. was 0.289 for the EQ-5D and 5.27 for the EQ-VAS. However, the MIC. INDIVIDUAL. for both the EQ-5D-3L Index (0.105) and EQ-VAS (-1) demonstrated poor-to-acceptable reliability. The MDC-90 was 0.023 for the EQ-5D-3L Index and 1.0 for the EQ-VAS. The PASS for the postoperative EQ-5D-3L Index and EQ-VAS scores predictive of patient satisfaction were 0.708 and 77.0, respectively. Conclusion. The meaningful values of the EQ-5D-3L Index and EQ-VAS scores can be used to measure clinically relevant changes in health-related quality of life in patients undergoing primary KA. Cite this article: Bone Joint Res 2022;11(9):619–628

Dysplasia of the hip, hypotonia, osteopenia, ligamentous laxity, and mental retardation increase the complexity of performing and managing patients with Down syndrome who require total hip replacement (THR). We identified 14 patients (six males, eight females, 21 hips) with Down syndrome and degenerative disease of the hip who underwent THR, with a minimum follow-up of two years from 1969 to 2009. In seven patients, bilateral THRs were performed while the rest had unilateral THRs. The mean clinical follow-up was 5.8 years (standard deviation (sd) 4.7; 2 to 17). The mean Harris hip score was 37.9 points (sd 7.8) pre-operatively and increased to 89.2 (sd 12.3) at final follow-up (p = 1x10^-9). No patient suffered a post-operative dislocation. In three patients, four hips had revision THR for aseptic loosening at a mean follow-up of 7.7 years (sd 6.3; 3 to 17). This rate of revision THR was higher than expected. Our patients with Down syndrome benefitted clinically from THR at mid-term follow-up.

Cite this article: Bone Joint J 2014;96-B:1455–8.

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain. Cite this article: Bone Joint Res 2022;11(7):439–452

This study was performed to review the safety and outcome of total shoulder replacements in patients who are ≥ 80 years of age. A total of 50 total shoulder replacements in 44 patients at a mean age of 82 years (80 to 89) were studied. Their health and shoulder status, the operation and post-operative course were analysed, including pain, movement, patient satisfaction, medical and surgical complications, radiographs, the need for revision surgery, and implant and patient survival. A total of 27 patients had an ASA classification of III or IV and medical abnormalities were common. Of the 13 shoulders with bony deficiency of the glenoid, nine required grafting. The duration of hospital stay was prolonged and blood transfusions were common. There were no peri-operative deaths. The mean follow-up was for 5.5 years (2 to 12). Pain was significantly reduced (p < 0.001) and movement improved in active elevation and both external and internal rotation (p < 0.001). Using the Neer scale for assessing outcome, 40 (80%) shoulders had an excellent or satisfactory result. There were medical or surgical complications in 17 cases. Four shoulders developed radiological evidence of loosened glenoid components, and three of these had a poor outcome. Three other shoulders required revision, two for instability. By the time of this review 39 of the patients had died from unrelated causes at a mean of 7.5 years (0.8 to 16.4) after surgery.

Total shoulder replacement is a relatively effective treatment in this elderly group of patients. However, there is a requirement for more intense patient care in the peri-operative period, and non-fatal medical or surgical complications are common. Most of these elderly patients will have a comfortable functional shoulder for the rest of their lives.