Aims. This study aims to identify the top unanswered research priorities in the field of knee surgery using consensus-based methodology. Methods. Initial research questions were generated using an online survey sent to all 680 members of the British Association for Surgery of the Knee (BASK). Duplicates were removed and a longlist was generated from this scoping exercise by a panel of 13 experts from across the UK who provided oversight of the process. A modified Delphi process was used to refine the questions and determine a final list. To rank the final list of questions, each question was scored between one (low importance) and ten (high importance) in order to produce the final list. Results. This consensus exercise took place between December 2020 and April 2022. A total of 286 clinicians from the BASK membership provided input for the initial scoping exercise, which generated a list of 105 distinct research questions. Following review and prioritization, a longlist of 51 questions was sent out for two rounds of the Delphi process. A total of 42 clinicians responded to the first round and 24 responded to the second round. A final list of 24 research questions was then ranked by 36 clinicians. The topics included arthroplasty, infection, meniscus, osteotomy, patellofemoral, cartilage, and ligament pathologies. The management of early osteoarthritis was the highest-ranking question. Conclusion. A Delphi exercise involving the BASK membership has identified the future research priorities in knee surgery. This list of questions will allow clinicians, researchers, and funders to collaborate in order to deliver high-quality research in knee surgery and further advance the care provided to patients with knee pathology. Cite this article: Bone Joint J 2024;106-B(7):662–668

Articular cartilage (AC) and subchondral bone (SB) are intimately intertwined, forming a complex unit called the AC-SB interface. Our recent studies have shown that cartilage and bone marrow are connected by a three-dimensional network of microchannels (i.e. cartilage-bone marrow microchannel connector; CMMC), which differ microarchitecturally in number, size and morphology depending on the maturation stage of the bone and the region of the joint. However, the pathological significance of CMMC is largely unknown. Here, we quantitatively assessed how CMMC microarchitecture relates to cartilage condition and regional differences in early idiopathic osteoarthritis (OA). Two groups of cadaveric female human femoral heads (intact cartilage vs early cartilage lesions) were identified and biopsy-based high-resolution micro-CT imaging was used. Subchondral bone (SB) thickness, CMMC number, maximum and minimum CMMC size, and CMMC morphology were quantified and compared between the two groups. The effect of joint region and cartilage condition on each dependent variable was examined. The number and morphology of CMMCs were influenced by the region of the joint, but not by the cartilage condition. On the other hand, the minimum and maximum CMMC size was modified by both joint location and cartilage condition. The smallest CMMCs were consistently found in the load bearing region (LBR) of the joint. Compared to healthy subjects, the size of the microchannels was increased in early OA, most notably in the non-load bearing region (NLBR) and the peripheral rim (PR) of the femoral head. In addition, subchondral bone thinning was observed in early OA as a localized event associated with areas of partial chondral defect. Our data suggest an enlargement of the SB microchannel network and a collective structural deterioration of the SB in early idiopathic OA

Osteoarthritis (OA) is the most common degenerative joint disorder. Its multifactorial etiology includes age, sex, joint overloading, genetic or nervous influences. In particular, the autonomic nervous system is increasingly gaining in importance. Its two branches, the sympathetic (SNS) and parasympathetic nervous system, are well-balanced under healthy conditions. OA patients seem to be prone to an autonomic imbalance and therefore, we analyzed their autonomic status. More than 200 participants including patients with early and late stage knee OA (before and 1 year after knee replacement surgery) and healthy probands (age-matched) were analyzed. Heart rate variability was measured via electrocardiogram to assess long-term sympathetic (low-frequency=LF) and parasympathetic (high-frequency=HF, pRR50) activities or general variability (RMSSD, SDRR). Serum cortisol concentrations were measured by ELISA. Perceived chronic stress (PSQ) was assessed via questionnaire. Multivariant regression was performed for data analysis. LF/HF value of early OA was slightly increased compared to healthy controls but significantly higher compared to late OA patients before (p>0.05) and after TKR (p>0.01). HF in late OA patients before TKR was significantly decreased compared to patients after TKR (p>0.001) or healthy controls (p>0.05). Healthy probands exhibited the highest SDRR values, early OA patients had slightly lower levels and late OA patients before TKR displayed significantly reduced SDRR (p>0.001). The same differences were observed in pRR50 and RMSSD. Serum cortisol concentrations and PSQ scores increased in late OA patients before TKR. At the time point of TKR, women with beta blocker medication had significantly higher age (71 ± 9 years) than those without (63 ± 12 years)(p>0.01). An autonomic dysfunction with sympathetic dominance occurs in OA patients. The fact that beta blocker medication in women delayed the need of TKR indicates that SNS inhibition might counteract OA. Future therapeutic interventions for OA should consider a systemic approach with special regard on the ANS

Matrix metalloproteinase enzymes (MMPs) play a crucial role in the remodeling of articular cartilage, contributing also to osteoarthritis (OA) progression. The pericellular matrix (PCM) is a specialized space surrounding each chondrocyte, containing collagen type VI and perlecan. It acts as a transducer of biomechanical and biochemical signals for the chondrocyte. This study investigates the impact of MMP-2, -3, and -7 on the integrity and biomechanical characteristics of the PCM. Human articular cartilage explants (n=10 patients, ethical-nr.:674/2016BO2) were incubated with activated MMP-2, -3, or -7 as well as combinations of these enzymes. The structural degradative effect on the PCM was assessed by immunolabelling of the PCM's main components: collagen type VI and perlecan. Biomechanical properties of the PCM in form of the elastic moduli (EM) were determined by means of atomic force microscopy (AFM), using a spherical cantilever tip (2.5µm). MMPs disrupted the PCM-integrity, resulting in altered collagen type VI and perlecan structure and dispersed pericellular arrangement. A total of 3600 AFM-measurements revealed that incubation with single MMPs resulted in decreased PCM stiffness (p<0.001) when compared to the untreated group. The overall EM were reduced by ∼36% for all the 3 individual enzymes. The enzyme combinations altered the biomechanical properties at a comparable level (∼36%, p<0.001), except for MMP-2/-7 (p=0.202). MMP-induced changes in the PCM composition have a significant impact on the biomechanical properties of the PCM, similar to those observed in early OA. Each individual MMP was shown to be highly capable of selectively degrading the PCM microenvironment. The combination of MMP-2 and -7 showed a lower potency in reducing the PCM stiffness, suggesting a possible interplay between the two enzymes. Our study showed that MMP-2, -3, and -7 play a direct role in the functional and structural remodeling of the PCM. Acknowledgements: This work was supported by the Faculty of Medicine of the University of Tübingen (grant number.: 2650-0-0)

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.

Abstract. Objectives. A promising therapy for early osteoarthritis (OA) is the transplantation of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs). The synovial fluid (SF) from a pre-clinical ovine model treated with hUC-MSCs has been profiled using proteomics and bioinformatics to elucidate potential mechanisms of therapeutic effect. Methods. Four weeks after a medial meniscus transection surgery, sheep were injected with 10. 7. hUC-MSCs in Phosphate Buffered Saline (PBS) or PBS only (n=7) and sacrificed at 12 weeks. SF was normalised for protein abundance (ProteoMiner. TM. ) and analysed using label-free quantitation proteomics. Bioinformatics analyses (Ingenuity Pathway Analysis (IPA) and STRING) were used to assess differentially regulated functions from the proteomic data. Human orthologues were identified for the ovine proteins using UniProt and DAVID resources and proteins that were ≥±1.3 fold differentially abundant between treatment groups, were included in the bioinformatics analyses. Results. hUC-MSC treated animals demonstrated significantly less joint space narrowing. Nineteen SF proteins were differentially abundant in treated cf. control sheep (FC±2.0; p<0.05). Biglycan (a small leucine-rich proteoglycan of the cartilage extracellular matrix) abundance was increased by 2.1 fold in treated compared to untreated sheep (p=0.024). IPA indicated that lipid synthesis (z-score=1.772; p=0.00267) and immune cell migration pathways (cell movement of mononuclear leukocytes: z-score=1.761; p=0.00259), amongst others, were likely to be activated in the treated sheep. Conversely, tissue damage (z-score=−2; p=0.00019), senescence (z-score=−1.981; p=0.00007) and necrosis (z-score=−1.728; p=0.00829) associated pathways as well as inflammation (z-score=−1.718; p=0.00057) and vascular permeability (z-score=−1.698; p=0.00002) were likely to be inhibited in treated cf. untreated sheep. Conclusions. hUC-MSC treatment prevented/delayed OA progression, demonstrated via a reduction in joint space narrowing. SF proteome bioinformatics revealed potential mechanisms of therapeutic action related to immunomodulation and the inhibition of multiple cell death, and tissue damage associated pathways. Further, a potential predicted upregulation in lipid synthesis in treated sheep represents a novel mechanism warranting further investigation. Additional work is required to validate these discovery phase proteomic findings in studies which specifically target and manipulate the proposed mechanisms highlighted. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Abstract. Objectives. Osteoarthritis (OA) is a painful and debilitating disorder of diarthroidal joints. Progressive degeneration of the cartilage extracellular matrix (ECM) together with abnormal chondrocyte characteristics occur leading to a switch to a fibroblast-like phenotype and production of mechanically-weak cartilage. Early changes to chondrocytes within human cartilage have been observed including chondrocyte swelling. [1]. together with the development of thin cytoplasmic processes which increase in number and length with degeneration. [2]. Changes to chondrocyte phenotype in degenerate cartilage are associated with F-actin redistribution and stress fibres (SF) formation, leading to morphologically-dedifferentiated (fibroblast-like) chondrocytes. [3,4]. It is unclear if these processes are a consequence of ‘passive’ cell swelling into a defective ECM or an ‘active’ event driven by changes in cell metabolism resulting in alterations to cell shape. To address this, we have quantified and compared the distribution and levels of F-actin, a key cytoskeletal protein involved in the formation of cytoplasmic processes, within in situ chondrocytes in non-degenerate and mildly degenerate human cartilage. Methods. Human femoral head cartilage was obtained from 21 patients [15 females, 6 males, average age 69.6yrs, (range 47–90yrs)] following femoral neck fracture, with Ethical Approval and patient's permission. Cartilage explants were removed from areas graded non-degenerate grade 0 (G0) or mildly degenerate grade 1 (G1) and cultured for up to 3wks in Dulbecco's Modified Eagle's Medium (DMEM) +/− 25% human serum (HS). In situ chondrocytes were stained with CMFDA (5-chloromethylfluoresceindiacetate, Cell-Tracker Green®) and phalloidin (F-actin labelling) and imaged by confocal microscopy and analysed quantitatively using ImageJ and Imaris® software. Results. There were significant increases in the total amount (TA) of F-actin and its distribution [intense punctuate (IP) and intense areas (IA)] between the whole chondrocyte populations of G0 and G1 cartilage (P=0.0356; 0.0112; 0.016, respectively). Where the volume of chondrocytes was divided into normal (<1000 µm³) and swollen (≥1000 µm³) cells, F-actin TA increased in swollen cells (P=0.036 within G0 and G1, and P=0.0009 between grades) compared to chondrocytes of normal volume in each grade. Moreover, IP and IA within and between G0 and G1 were higher compared to normal chondrocytes (with P<0.0001 for IP and P<0.001 for IA). In addition, tissue culture experiments demonstrated that 90% of chondrocytes with cytoplasmic processes had strong F-actin intensity (either IP or IA with P<0.0001). Furthermore, 83% of this F-actin was associated with cytoplasmic processes, with >65% situated at the base of the process (P<0.0001). Conclusions. The increases in chondrocyte F-actin levels (TA) and its localisation (IP, IA) appear to be associated with cell swelling and development of cytoplasmic processes, which are both characteristics of early OA cartilage. [1]. This suggests the formation of chondrocyte cytoplasmic processes is an ‘active’ event potentially involving changes to matrix metabolism rather than a ‘passive’ cell swelling into a defective extracellular matrix. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Abstract. Objectives. Osteoarthritis (OA) is a complex joint disorder characterised by the loss of extracellular matrix (ECM) leading to cartilage degeneration. Changes to cartilage cell (chondrocyte) behaviour occur including cell swelling, the development of fine cytoplasmic processes and cell clustering leading to changes in cell phenotype and development of focal areas of mechanically-weak fibrocartilaginous matrix. [1]. To study the sequence of events in more detail, we have investigated the changes to in situ chondrocytes within human cartilage which has been lightly scraped and then cultured with serum. Methods. Human femoral heads were obtained with Ethical permission and consent from four female patients (mean age 74 yrs) undergoing hip arthroplasty following femoral neck fracture. Osteochondral explants of macroscopically-normal cartilage were cultured as a non-scraped control, or scraped gently six times with a scalpel blade and both maintained in culture for up to 2wks in Dulbecco's Modified Eagle's Medium (DMEM) with 25% human serum (HS). Explants were then labelled with CMFDA (5-chloromethylfluorescein-diacetate) and PI (propidium iodide) (10μM each) to identify the morphology of living or dead chondrocytes respectively. Explants were imaged using confocal microscopy and in situ chondrocyte morphology, volume and clustering assessed quantitatively within standardised regions of interest (ROI) using Imaris. ®. imaging software. Results. Within 2wks of culture with HS, chondrocyte volume increased significantly from 412±9.3µm. 3. (unscraped) at day 0 to 724±16.6 µm. 3. (scraped) [N(n) = 4(380)] (P=0.0002). Chondrocyte clustering was a prominent feature of HS culture as the percentage of clusters in the cell population increased with scraping from 4.8±1.4% to 14.9±3.9% [N(n) = 4(999)] at week 2 (P=0.0116). In addition, the % of the chondrocyte population within clusters increased from approximately 38% to 60%, and the number of cells per cluster increased significantly from 3.2±0.08 to 4±0.22 (P=0.031). The development of abnormal ‘fibroblastic-like’ chondrocyte morphology demonstrating long (>5µm) cytoplasmic processes also occurred, however the time course of this was more variable. For some samples, clustering occurred before abnormal morphology, but for others the opposite occurred. Typically, by the second week, 17±2.64% of the cell population had processes and this increased to 22±4.02% [N(n) = 4(759)] with scraping. Conclusions. Scraping the cartilage will remove surface constituents including lubricants (e.g. lubricin, hyaluronic acid, phospholipids), extracellular matrix constituents (collagen, proteoglycans – potentially the ‘lamina splendens’) and cells (chondrocytes and mesenchymal stromal cells (MSCs)). Although we do not know which of these component(s) is important, the effect is to dramatically increase the permeation of serum factors into the cartilage matrix and signal the development of cytoplasmic processes, cell clustering and swelling. It is notable that these cellular changes are similar to those occurring in early OA. [1]. This raises the interesting possibility that scraped cartilage cultured with human serum recapitulates some of the changes to in situ chondrocytes during early stages of cartilage degeneration and as such, could be a useful model for following the deleterious changes to matrix metabolism. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

The October 2023 Children’s orthopaedics Roundup³⁶⁰ looks at: Outcomes of open reduction in children with developmental hip dislocation: a multicentre experience over a decade; A torn discoid lateral meniscus impacts lower-limb alignment regardless of age; Who benefits from allowing the physis to grow in slipped capital femoral epiphysis?; Consensus guidelines on the management of musculoskeletal infection affecting children in the UK; Diagnosis of developmental dysplasia of the hip by ultrasound imaging using deep learning; Outcomes at a mean of 13 years after proximal humeral fracture during adolescence; Clubfeet treated according to Ponseti at four years; Controlled ankle movement boot provides improved outcomes with lower complications than short leg walking cast.

Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA.

Cite this article: Bone Joint Res 2023;12(9):536–545.

Aims

Focal knee arthroplasty is an attractive alternative to knee arthroplasty for young patients because it allows preservation of a large amount of bone for potential revisions. However, the mechanical behaviour of cartilage has not yet been investigated because it is challenging to evaluate in vivo contact areas, pressure, and deformations from metal implants. Therefore, this study aimed to determine the contact pressure in the tibiofemoral joint with a focal knee arthroplasty using a finite element model.

Abstract. Introduction. Previous research has demonstrated no clinically significant benefit of arthroscopic meniscectomy in patients with a meniscal tear, however, patients included in these studies would not meet current treatment recommendations. Prior to further randomised controlled trials (RCTs) research is needed to understand a younger population in more detail. Aim. To describe the baseline characteristics of patients with a meniscal tear and explore any association between baseline characteristics and outcome. Methodology. A prospective, national multicentre cohort study was performed recruiting patients aged 18 to 55 presenting to secondary care. MRI analysis of arthritis was performed using Whole Organ Magnetic Resonance Imaging Score (WORMS) and bone shape analysis. Outcomes included the Western Ontario Meniscal Evaluation Tool (WOMET) and Knee Injury and Osteoarthritis Outcome Score (KOOS4) at 12 months. Results. 150 participants were recruited across eight sites with a mean age of 43.47 (SD 9.63). MRI analysis using WORMS score and bone shape analysis revealed no or early osteoarthritis. At 12 months, 67 (44.67%) of participants were managed non-operatively and 68 (45.33%) were operatively. Participants in the operative group were significantly younger with a lower BMI (p<0.05). A stepwise logistic regression model including 17 characteristics revealed that only baseline score and surgery significantly affected 12-month WOMET and KOOS4. Conclusion. This study in contrast to previous trials demonstrated a benefit of surgery for patients with a meniscal tear. The METRO study demonstrates that it is feasible to recruit younger patients and a future RCT is required using the study population included in this cohort

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.

Satisfactory intermediate and long-term results of rotational acetabular osteotomy (RAO) for the treatment of early osteoarthritis secondary to developmental dysplasia of the hip have been reported. The purpose of this study is to examine the 30-year results of RAO. Between 1987 and 1994, we treated 49 patients (55 hips) with RAO for diagnosis of pre- OA or early-stage OA. Of those patients, 35 patients (43 hips) were available at a minimum of 28 years. The follow-up rate was 78.2% and the mean follow-up was 30.5 years. The mean age at the time of surgery was 34 years. Clinical evaluation was performed with the Merle d'Aubigne and Postel rating scale, and radiographic analyses included measurements of the center-edge angle, acetabular roof angle, and head lateralization index on preoperative, postoperative AP radiographs of the pelvis. Postoperative joint congruency was classified into four grades. The radiographic evidence of progression of OA was defined as the minimum joint space less than 2.5mm. The mean preoperative clinical score was 14.0, which improved to a mean of 15.3 at the time of the latest follow-up. The mean center-edge angle improved from 0.6° preoperatively to 34° postoperatively, the mean acetabular roof angle improved from 28.4°preoperatively to 1.0°postoperatively, the mean head lateralization index improved from 0.642 preoperatively to 0.59 postoperatively. Postoperative joint congruency was excellent in 11 hips, good in 29 hips, and fair in 3 hips. Nineteen patients (20 hips) had radiographic OA progression, and 10 patients (11 hips) were converted to THA. Kaplan-Meier survivorship analysis, with radiographic OA progression as the end point, predicted survival of 75.6% at 20 years and 48.8% at 30 years, and with THA conversion as the end point, 90.2% at 20 years and 71.2% at 30 years. The RAO is an effective surgical procedure for symptomatic dysplastic hips of pre- and early-stage OA and could change the natural history of the dysplastic hip

It is unclear whether patients with early radiographic osteoarthritis (OA) but severe hip symptoms benefit from total hip replacement (THR). We aimed to assess which factors were associated with successful THR in this patient group. From a consecutive series of 1,935 patients undergoing THR we identified 70 (3.6%) patients with early OA (Kellgren and Lawrence (KL) grades 0-2). These were compared with 200 patients with advanced OA (KL grades 3–4). Outcomes were Oxford Hip Scores (OHS), EQ5D and EQ-VAS scores; compared pre-operatively with one year post-operatively. We investigated which clinical and radiographic (plain x-ray, CT, MRI) features predicted successful THR in the early OA group. Success was defined as reaching a postoperative OHS≥42. The early OA group were significantly younger (61 vs 66 years; P=0.0035). There were no significant differences in body mass index, ASA grade or gender. After adjusting for confounders, the advanced OA group had a significantly greater percentage of possible change (PoPC) in OHS (75.8% versus 50.4%; P<0.0001) and improvement in EQ5D (0.151 versus 0.002; P<0.0001). There were no significant differences in complication, revision or readmission rates. In the early OA group, we identified 16/70 (22.9%) patients who had a ‘successful’ THR. Of those with early OA, 38 patients had pre-operative CT or MRI scans. Patients who had a ‘successful’ THR were significantly more likely to have subchondral cysts on CT/MRI (91.7% versus 57.7%; P=0.0362). The presence of cysts on CT/MRI was associated with a significantly greater PoPC in OHS (61.6% versus 38.2%; P=0.0353). The combination of cysts and joint space width (JSW) <1mm was associated with a PoPC of 68%. Plain radiographs were found to significantly underestimate the narrowest JSW compared to CT/MRI (2.4mm versus 1.0mm; P<0.0001). We advise caution in performing THRs in patients with early OA (KL grades 0-2) on plain radiographs. We advocate pre-operative cross-sectional imaging (CT or MRI) in these patients. In the absence of cysts on cross-sectional imaging, a THR seems unlikely to provide a satisfactory outcome

The June 2023 Wrist & Hand Roundup³⁶⁰ looks at: Residual flexion deformity after scaphoid nonunion surgery: a seven-year follow-up study; The effectiveness of cognitive behavioural therapy for patients with concurrent hand and psychological disorders; Bite injuries to the hand and forearm: analysis of hospital stay, treatment, and costs; Outcomes of acute perilunate injuries - a systematic review; Abnormal MRI signal intensity of the triangular fibrocartilage complex in asymptomatic wrists; Patient comprehension of operative instructions with a paper handout versus a video: a prospective, randomized controlled trial; Can common hand surgeries be undertaken in the office setting?; The effect of corticosteroid injections on postoperative infections in trigger finger release.

Cite this article: Bone Joint Res 2023;12(5):309–310.

Cite this article: Bone Joint Res 2023;12(5):306–308.