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Objective The objective of this study is to establish which patient and lesion characteristics are related to the clinical outcome after microfracture of cartilage defects in the knee. Study design Systematic review. Methods After preregistration, PubMed, Embase, and Cochrane were searched for studies that analyzed prognostic factors for the outcome of microfracture treatment in the knee. The criteria for inclusion were outcome measured using Patient-Reported Outcome Measures (PROMs), a clinical study with ≥10 participants receiving microfracture, and a minimal follow-up period of 1 year. Results For none of the investigated prognostic factors, effect size reporting was sufficiently homogeneous to conduct a meta-analysis. However, a majority of the included studies identified higher age, larger lesion size, longer preoperative symptom duration, and previous surgery on the ipsilateral knee, especially meniscectomy and anterior cruciate ligament reconstruction, as factors that are reported to be correlated to a less favorable outcome. A lesion location that does not include the trochlea or the patellofemoral joint and is not weightbearing, a nondegenerative mechanism of injury, and a single lesion were reported as factors that predict a favorable outcome. As to gender, body mass index, preoperative activity level, smoking, and concomitant knee surgery, the included articles were inconclusive or no effect was reported. Conclusions Several factors correlated with the clinical result after microfracture treatment. However, the information on the effect sizes of the influence on clinical outcome is incomplete due to poor reporting. Large-scale registries or pooling of homogeneous, well-reported data is needed to work toward prognostic models. That would be an important step toward personalized treatment.

The clinical success of osteochondral implants depends significantly on their surface properties. In vivo, an implant may roughen over time which can decrease its performance. The present study investigates whether changes in the surface texture of metal and two types of polycarbonate urethane (PCU) focal knee resurfacing implants (FKRIs) occurred after 6 and 12 months of in vivo articulation with native goat cartilage. PCU implants which differed in stem stiffness were compared to investigate whether the stem fixating the implant in the bone influences surface topography. Using optical profilometry, 19 surface texture parameters were evaluated, including spatial distribution and functional parameters obtained from the material ratio curve. For metal implants, wear during in vivo articulation occurred mainly via material removal, as shown by the significant decrease of the core-valley transition from 91.5% in unused implants to 90% and 89.6% after 6 and 12 months, respectively. Conversely, for PCU implants, the wear mechanism consisted in either filling of the valleys or flattening of the surface by dulling of sharp peaks. This was illustrated in the change in roughness skewness from negative to positive values over 12 months of in vivo articulation. Implants with a softer stem experienced the most deformation, shown by the largest change in material ratio curve parameters. We therefore showed, using a detailed surface profilometry analysis, that the surface texture of metal and two different PCU FKRIs changes in a different way after articulation against cartilage, revealing distinct wear mechanisms of different implant materials.

Background: Realignment osteotomies is gaining popularity amongst Dutch orthopaedic surgeons. Exact numbers and used standards in clinical practice concerning osteotomies are unknown due to the absence of a national registry. The aim of this study was to inves-tigate the national statistics of performed osteotomies, utilized clinical workups, surgical techniques, and post-operative rehabilitation standards in the Netherlands. Method: Dutch orthopaedic surgeons, all members of the Dutch Knee Society, received a web-based survey between January and March 2021. This electronic survey contained 36 questions, subdivided into: general surgeon-related information, number of performed osteotomies, inclusion of patients, clinical workup, surgical techniques, and post-operative management. Results: 86 orthopaedic surgeons filled in the questionnaire, of whom 60 perform realign-ment osteotomies around the knee. All the 60 responders (100%) perform high tibial osteo-tomies and 63.3% additionally perform distal femoral osteotomies, while 30% perform double level osteotomies. Discrepancies in surgical standards were reported regarding to inclusion criteria, clinical workup, surgical techniques, and post-operative strategies. Conclusions: In conclusion, this study got more insight in knee osteotomy clinical practices as applied by Dutch orthopaedic surgeons. However, there are still important discrepancies which pleads for more standardization based on available evidence. A (inter)national knee osteotomy registry, and even more so, a (inter)national registry for joint preserving surgeries could be helpful to achieve more standardization and treatment insights. Such a registry could improve all aspects of osteotomies and its combinations with other joint-preserving interventions towards evidence for personalised treatments. (c) 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Summary Objective Early and non-invasive detection of osteoarthritis (OA) is required to enable early treatment and monitoring of interventions. Some of the earliest signs of OA are the change in proteoglycan and collagen composition. The aim of this study is to establish the relations between quantitative magnetic resonance imaging (MRI) and biochemical concentration and organization in knee articular cartilage. Methods A preregistered systematic literature review was performed using the databases PubMed and Embase. Papers were included if quantitative MRI and a biochemical assay or polarized light microscopy (PLM) was performed on knee articular cartilage, and a quantified correlation was described. The extracted correlations were pooled using a random effects model. Results 21 papers were identified. The strongest pooled correlation was found for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) vs. proteoglycan concentration (r=0.59). T1ρ relaxation times are inversely correlated to proteoglycan concentration (r=-0.54). A weak correlation between T2 relaxation times and proteoglycans was found (r=-0.38). No correlation between T2 relaxation time and collagen concentration was found (r=-0.02). A heterogeneous set of correlations between T2 relaxation times and PLM were identified, including strong correlations to anisotropy. Conclusion DGEMRIC measures are significantly correlated to proteoglycan concentration. The needed contrast agent is however a disadvantage; the T1ρ sequence was found as a non-invasive alternative. Remarkably, no correlation was found between T2 relaxation times and collagen concentration. T2 relaxation times is related to organization, rather than concentration of collagen fibers. Prospero ID CRD42020168337.

Mass spectrometry imaging (MSI) is a powerful technique enabling the visualization of the spatial distribution of different molecules in tissue biopsies with different pathologies. Sample handling and preparing adipose tissue for MSI is challenging and prone to molecular delocalization due to tissue melting. In this work, we developed a method for matrix-assisted laser desorption/ionization (MALDI)-MSI to study lipids in human infrapatellar fat pad (IPFP), a biomarker source in musculoskeletal pathologies, while preserving molecular spatial distribution. Cryosectioning at 15 μm with a temperature below -30 °C, thaw-mounting, and sublimation, was demonstrated to preserve IPFP's heterogeneous appearance and spatial distribution of lipids.

For knee osteoarthritis and related conditions, analysis of biomarkers hold promise to improve early diagnosis and/or offer patient-specific treatment. To compare biomarker analyses, reliable, high-quality biopsies are needed. The aim of this work is to summarize the literature on the current best practices of biopsy of the synovium and synovial fluid arthrocentesis. Therefore, PubMed, Embase and Web of Science were systematically searched for articles that applied, demonstrated, or evaluated synovial biopsies or arthrocentesis. Expert recommendations and applications were summarized, and evidence for superiority of techniques was evaluated. Thirty-one studies were identified for inclusion. For arthrocentesis, the superolateral approach in a supine position, with a 0°-30° knee flexion was generally recommended. 18-gage needles, mechanical compression and ultrasound-guidance were found to give superior results. For blind and image-guided synovial biopsy techniques, superolateral and infrapatellar approaches were recommended. Single-handed tools were preconized, including Parker-Pearson needles and forceps. Sample quantity ranged approximately from 2 to 20. Suggestions were compiled for arthrocentesis regarding approach portal and patient position. Further evidence regarding needle size, ultrasound-guidance and mechanical compression were found. More comparative studies are needed before evidence-based protocols can be developed.

Objective The potential chondroprotective effect of celecoxib, a nonsteroidal anti-inflammatory drug and selective cyclooxygenase-2 inhibitor used to reduce pain and inflammation in knee osteoarthritis patients, is disputed. This study aimed at investigating the chondroprotective effects of celecoxib on (1) human articular cartilage explants and (2) in an in vivo osteoarthritis rat model. Design Articular cartilage explants from 16 osteoarthritis patients were cultured for 24 hours with celecoxib or vehicle. Secreted prostaglandins (prostaglandin E2, prostaglandin F2α, prostaglandin D2) and thromboxane B2 (TXB2) concentrations were determined in medium by ELISA, and protein regulation was measured with label-free proteomics. Cartilage samples from 7 of these patients were analyzed for gene expression using real-time quantitative polymerase chain reaction. To investigate the chondroprotective effect of celecoxib in vivo, 14 rats received an intra-articular injection of celecoxib or 0.9% NaCl after osteoarthritis induction by anterior cruciate ligament transection and partial medial meniscectomy (ACLT/pMMx model). Histopathological scoring was used to evaluate osteoarthritis severity 12 weeks after injection. Results Secretion of prostaglandins, target of Nesh-SH3 (ABI3BP), and osteonectin proteins decreased, whereas tissue inhibitor of metalloproteinase 2 (TIMP-2) increased significantly after celecoxib treatment in the human ( ex vivo) explant culture. Gene expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 (ADAMTS4/5) and metalloproteinase 13 (MMP13) was significantly reduced after celecoxib treatment in human cartilage explants. Cartilage degeneration was reduced significantly in an in vivo osteoarthritis knee rat model. Conclusions Our data demonstrated that celecoxib acts chondroprotective on cartilage ex vivo and a single intra-articular bolus injection has a chondroprotective effect in vivo.

The potential chondroprotective effect of celecoxib, a nonsteroidal anti-inflammatory drug and selective cyclooxygenase-2 inhibitor used to reduce pain and inflammation in knee osteoarthritis patients, is disputed. This study aimed at investigating the chondroprotective effects of celecoxib on (1) human articular cartilage explants and (2) in anArticular cartilage explants from 16 osteoarthritis patients were cultured for 24 hours with celecoxib or vehicle. Secreted prostaglandins (prostaglandin ESecretion of prostaglandins, target of Nesh-SH3 (ABI3BP), and osteonectin proteins decreased, whereas tissue inhibitor of metalloproteinase 2 (TIMP-2) increased significantly after celecoxib treatment in the human (Our data demonstrated that celecoxib acts chondroprotective on cartilage

Osteoarthritis (OA) is a multifactorial pathology and comprises a wide range of distinct phenotypes. In this context, the characterization of the different molecular profiles associated with each phenotype can improve the classification of OA. In particular, OA can coexist with type 2 diabetes mellitus (T2DM). This study investigates lipidomic and proteomic differences between human OA/T2DM(-) and OA/T2DM(+) cartilage through a multimodal mass spectrometry approach. Human cartilage samples were obtained after total knee replacement from OA/T2DM(-) and OA/T2DM(+) patients. Label-free proteomics was employed to study differences in protein abundance and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) for spatially resolved-lipid analysis. Label-free proteomic analysis showed differences between OA/T2DM(-) and OA/T2DM(+) phenotypes in several metabolic pathways such as lipid regulation. Interestingly, phospholipase A2 protein was found increased within the OA/T2DM(+) cohort. In addition, MALDI-MSI experiments revealed that phosphatidylcholine and sphingomyelin species were characteristic of the OA/T2DM(-) group, whereas lysolipids were more characteristic of the OA/T2DM(+) phenotype. The data also pointed out differences in phospholipid content between superficial and deep layers of the cartilage. Our study shows distinctively different lipid and protein profiles between OA/T2DM(-) and OA/T2DM(+) human cartilage, demonstrating the importance of subclassification of the OA disease for better personalized treatments.

Purpose A histological study of a structure between fgvbthe posterior horn of the lateral meniscus and the anterior cruciate ligament. Methods Bilateral fresh-frozen cadaveric knees of two male donors (age 71 and 76 years) with no history of prior knee injury were examined. All dissections were performed by one experienced orthopaedic surgeon. Haematoxylin and Eosin staining was used to reveal tissue morphology. Goldner trichrome staining was used to evaluate the connective tissue. S100 and PGP 9.5 labelling were used for immunohistochemical analysis. Results In all cadaveric knees, a structure between the posterior horn of the lateral meniscus and the anterior cruciate ligament was identified. Histological analysis confirmed the ligamentous nature of this structure. Furthermore, Golgi tendon organs were observed within the ligamentous structure. Conclusion This is the first study showing the presence of mechanoreceptors within the ligamentous structure between the posterior horn of the lateral meniscus and the anterior cruciate ligament. The ligamentous structure could contribute to stability of the knee by providing proprioceptive input, while preservation of the ligamentous structure might ensure a better functional outcome after surgery.

Knee osteoarthritis (OA) is a condition mainly characterized by cartilage degradation. Currently, no effective treatment exists to slow down the progression of OA-related cartilage damage. Selective COX-2 inhibitors may, next to their pain killing properties, act chondroprotective in vivo. To determine whether the route of administration is important for the efficacy of the chondroprotective properties of selective COX-2 inhibitors, a systematic review was performed according to the PRISMA guidelines. Studies investigating OA-related cartilage damage of selective COX-2 inhibitors in vivo were included. Nine of the fourteen preclinical studies demonstrated chondroprotective effects of selective COX-2 inhibitors using systemic administration. Five clinical studies were included and, although in general non-randomized, failed to demonstrate chondroprotective actions of oral selective COX-2 inhibitors. All of the four preclinical studies using bolus intra-articular injections demonstrated chondroprotective actions, while one of the three preclinical studies using a slow release system demonstrated chondroprotective actions. Despite the limited evidence in clinical studies that have used the oral administration route, there seems to be a preclinical basis for considering selective COX-2 inhibitors as disease modifying osteoarthritis drugs when used intra-articularly. Intra-articularly injected selective COX-2 inhibitors may hold the potential to provide chondroprotective effects in vivo in clinical studies.

Purpose of Review Osteoarthritis (OA) is the most common forms of arthritis in the general population, accounting for more pain and functional disability than any other musculoskeletal disease. There are currently no approved disease modifying drugs for OA. In the absence of effective pharmacotherapy, many patients with OA turn to nutritional supplements and nutraceuticals, including collagen derivatives. Collagen hydrolyzates and ultrahydrolyzates are terms used to describe collagens that have been broken down into small peptides and amino acids in the presence of collagenases and high pressure. Recent Findings This article reviews the relevant literature and serves as a White Paper on collagen hydrolyzates and ultrahydrolyzates as emerging supplements often advertised to support joint health in OA. Collagen hydrolyzates have demonstrated some evidence of efficacy in a handful of small scale clinical trials, but their ability to treat and reverse advanced joint disease remains highly speculative, as is the case for other nutritional supplements. Summary The aim of this White Paper is to stimulate research and development of collagen-based supplements for patients with OA and other musculoskeletal diseases at academic and industrial levels. This White Paper does not make any treatment recommendations for OA patients in the clinical context, but simply aims to highlight opportunities for scientific innovation and interdisciplinary collaboration, which are crucial for the development of novel products and nutritional interventions based on the best available and published evidence.

Knee joint distraction (KJD) treatment has shown cartilage repair and clinical improvement in patients with osteoarthritis, as has high tibial osteotomy (HTO). Following KJD, TGFβ-1 and IL-6 were increased in synovial fluid (SF), factors related to cartilage regeneration, but also to osteophyte formation. As such, osteophyte formation after both joint-preserving treatments was studied. Radiographic osteophyte size was measured before, one year, and two years after treatment. Changes were compared with natural progression in patients from the CHECK cohort before undergoing total knee arthroplasty. An additional KJD cohort underwent SF aspiration, and one-year Altman osteophyte score changes were compared to SF-marker changes during treatment. After two years, both KJD (n = 58) and HTO (n = 38) patients showed an increase in osteophyte size (+6.2 mm2 and +7.0 mm2 resp., both p &lt, 0.004), with no significant differences between treatments (p = 0.592). Untreated CHECK patients (n = 44) did not show significant two-year changes (+2.1 mm2, p = 0.207) and showed significant differences with KJD and HTO (both p &lt, 0.044). In SF aspiration patients (n = 17), there were significant differences in TGFβ-1 changes (p = 0.044), but not IL-6 (p = 0.898), between patients with a decrease, no change, or increase in osteophyte Altman score. Since KJD and HTO showed joint space widening and clinical improvement accompanied by osteophyte formation, increased osteophytosis after joint-preserving treatments may be a bystander effect of cartilage repair activity related to intra-articular factors like TGFβ-1 and raises questions regarding osteophyte formation as solely characteristic of the joint degenerative process.

Background: Focal cartilage defects are often debilitating, possess limited potential for regeneration, are associated with increased risk of osteoarthritis, and are predictive for total knee arthroplasty. Cartilage repair studies typically focus on the outcome in younger patients, but a high proportion of treated patients are 40 to 60 years of age (ie, middle-aged). The reality of current clinical practice is that the ideal patient for cartilage repair is not the typical patient. Specific attention to cartilage repair outcomes in middle-aged patients is warranted. Purpose: To systematically review available literature on knee cartilage repair in middle-aged patients and include studies comparing results across different age groups. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic search was performed in EMBASE, MEDLINE, and the Cochrane Library database. Articles were screened for relevance and appraised for quality. Results: A total of 21 articles (mean Coleman Methodology Score, 64 points) were included. Two out of 3 bone marrow stimulation (BMS) studies, including 1 using the microfracture technique, revealed inferior clinical outcomes in middle-aged patients in comparison with younger patients. Nine cell-based studies were included showing inconsistent comparisons of results across age groups for autologous chondrocyte implantation (ACI). Bone marrow aspirate concentrate showed age-independent results at up to 8 years of follow-up. A negative effect of middle age was reported in 1 study for both ACI and BMS. Four out of 5 studies on bone-based resurfacing therapies (allografting and focal knee resurfacing implants [FKRIs]) showed age-independent results up to 5 years. One study in only middle-aged patients reported better clinical outcomes for FKRIs when compared with biological repairs. Conclusion: Included studies were heterogeneous and had low methodological quality. BMS in middle-aged patients seems to only result in short-term improvements. More research is warranted to elucidate the ameliorating effects of cell-based therapies on the aging joint homeostasis. Bone-based therapies seem to be relatively insensitive to aging and may potentially result in effective joint preservation. Age subanalyses in cohort studies, randomized clinical trials, and international registries should generate more evidence for the large but underrepresented (in terms of cartilage repair) middle-aged population in the literature.

Introduction: Knee osteoarthritis (OA) is a joint disease, affecting multiple tissues in the joint. Early detection and intervention may delay OA development and avoid total knee arthroplasty. Specific biomarker profiles for early detection and guiding clinical decision-making of OA have not yet been identified. One technique that can contribute to the finding of this ‘OA biomarker’ is mass spectrometry (MS), which offers the possibility to analyze different molecules in tissues or fluids. Several proteomic, lipidomic, metabolomic and other–omic approaches aim to identify these molecular profiles; however, variation in methods and techniques complicate the finding of promising candidate biomarkers. Areas covered: In this systematic review, we aim to provide an overview of molecules in knee OA patients. Possible biomarkers in several tissue types of OA and non-OA patients, as well as current limitations and possible future suggestions will be discussed. Expert opinion: According to this review, we do not believe one specific biomarker will function as predictive molecule for OA. Likely, a group of molecules will give insight in OA development and possible therapeutic targets. For clinical implementation of MS-analysis in clinical decision-making, standardized procedures, large cohort studies and sharing protocols and data is necessary.

Treatment of osteoarthritis (OA) is mainly symptomatic by alleviating pain to postpone total joint replacement. Bone morphogenetic protein 7 (BMP7) is a candidate morphogen for experimental OA treatment that favorably alters the chondrocyte and cartilage phenotype. Intra-articular delivery and sustained release of a recombinant growth factor for treating OA are challenging, whereas the use of peptide technology potentially circumvents many of these challenges. In this study, we screened a high-resolution BMP7 peptide library and discovered several overlapping peptide sequences from two regions in BMP7 with nanomolar bioactivity that attenuated the pathological OA chondrocyte phenotype. A single exposure of OA chondrocytes to peptides p[63−82] and p[113−132] ameliorated the OA chondrocyte phenotype for up to 8 days, and peptides were bioactive on chondrocytes in OA synovial fluid. Peptides p[63−82] and p[113−132] required NKX3-2 for their bioactivity on chondrocytes and provoke changes in SMAD signaling activity. The bioactivity of p[63−82] depended on specific evolutionary conserved sequence elements common to BMP family members. Intra-articular injection of a rat medial meniscal tear (MMT) model with peptide p[63−82] attenuated cartilage degeneration. Together, this study identified two regions in BMP7 from which bioactive peptides are able to attenuate the OA chondrocyte phenotype. These BMP7-derived peptides provide potential novel disease-modifying treatment options for OA., Graphical abstract, BMP7 is a candidate morphogen for experimental osteoarthritis treatment that favorably alters the chondrocyte and cartilage phenotype. This study discovered two regions in BMP7 from which bioactive peptides are able to attenuate the OA chondrocyte phenotype. These BMP7-derived peptides provide potential novel disease-modifying treatment options for OA.

Osteoarthritis (OA) is one of the most common musculoskeletal diseases, characterized by the progressive deterioration of articular cartilage. Although the disease has been well studied in the past few years, the endogenous metabolic composition and more importantly the spatial information of these molecules in cartilage is still poorly understood. Matrix-assisted laser desorption/ ionization (MALDI) mass spectrometry imaging (MSI) has been previously used for the investigation of the bimolecular distribution of proteins and lipids through the in situ analysis of cartilage tissue sections. MALDI-MSI as a tool to detect metabolites remains challenging, as these species have low abundance and degrade rapidly. In this work, we present a complete methodology, from sample preparation to data analysis for the detection of endogenous metabolites on cartilage by MSI. Our results demonstrate for the first time the ability to detect small molecules in fragile, challenging tissues through an optimized protocol, and render MSI as a tool towards a better understanding of OA.

Background: Negotiating stairs is an important activity of daily living that is also associated with large loads on the knee joint. In medial compartment knee osteoarthritis, the knee adduction moment during level walking is considered a marker for disease severity. It could be argued that the discriminative capability of this parameter is even better if tested in a strenuous stair negotiation task.Research question: What is the relation with knee osteoarthritis on the knee adduction moment during the stance phase of both stair ascent and descent in patients with and without obesity?Methods: This case control study included 22 lean controls, 16 lean knee osteoarthritis patients, and 14 obese knee osteoarthritis patients. All subjects ascended and descended a two-step staircase at a self-selected, comfortable speed. Three-dimensional motion analysis was performed to evaluate the knee adduction moment during stair negotiation.Results: Obese knee osteoarthritis patients show a prolonged stance time together with a more flattened knee adduction moment curve during stair ascent. Normalized knee adduction moment impulse, as well as the first and second peaks were not different between groups. During stair descent, a similar increase in stance time was found for both osteoarthritis groups.Significance: The absence of a significant effect of groups on the normalized knee adduction moment during stair negotiation may be explained by a lower ambulatory speed in the obese knee osteoarthritis group, that effectively lowers vertical ground reaction force. Decreasing ambulatory speed may be an effective strategy to lower knee adduction moment during stair negotiation.

Objective Hospitalization is generally accompanied by changes in food intake. Patients typically receive hospital meals upon personal preference within the framework of the food administration services of the hospital. In the present study, we assessed food provision and actual food and snack consumption in older patients admitted for elective hip or knee arthroplasty. Design A prospective observational study. Setting Orthopedic nursing ward of the Maastricht University Medical Centre+. Participants In the present study, n=101 patients (age: 67±10 y; hospital stay: 6.1±1.8 d) were monitored during hospitalization following elective hip or knee arthroplasty. Measurements Energy and protein provided by self-selected hospital meals and snacks, and actual energy and protein (amount, distribution, and source) consumed by patients was weighed and recorded throughout 1–6 days. Results Self-selected meals provided 6.5±1.5 MJ·d-1, with 16, 48, and 34 En% provided as protein, carbohydrate, and fat, respectively. Self-selected hospital meals provided 0.75±0.16 and 0.79±0.21 g·kg-1·d-1 protein in males and females, respectively. Actual protein consumption averaged merely 0.59±0.18 and 0.50±0.21 g·kg-1·d-1, respectively. Protein consumption at breakfast, lunch, and dinner averaged 16±8, 18±9, and 20±6 g per meal, respectively. Conclusions Though self-selected hospital meals provide patients with ∼0.8 g·kg-1·d-1 protein during short-term hospitalization, actual protein consumption falls well below 0.6 g·kg-1·d-1 with a large proportion (∼32%) of the provided food being discarded. Alternative strategies are required to ensure maintenance of habitual protein intake in older patients admitted for elective orthopedic surgery. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s12603-019-1157-2 and is accessible for authorized users.

ObjectivesOsteoarthritis (OA) presents as a change in the chondrocyte phenotype and an imbalance between anabolic and catabolic processes. Age affects its onset and progression. Small nucleolar RNAs (SnoRNAs) direct chemical modification of RNA substrates to fine-tune spliceosomal and rRNA function, accommodating changing requirements for splicing and protein synthesis during health and disease. This study was undertaken to examine how changes in snoRNAs expression may have a role in OA.MethodsArticular cartilage from young, old and OA knees was used in a microarray study to identify alterations in snoRNA expression. Changes in expression of snoRNAs in OA-like conditions were studied in chondrocytes using interleukin-1 and OA synovial fluid. SNORD26 and SNORD96A knockdown and overexpression were undertaken using antisense oligonucleotides and overexpression plasmids.ResultsWe identified panels of snoRNAs differentially expressed due to ageing (including SNORD96A, SNORD44) and OA (including SNORD26 and SNORD116) and findings were validated in an independent cohort.In vitroexperiments using OA-like conditions affected snoRNA expression. Knockdown or overexpression of SNORD26 or SNORD96A resulted in changes in chondrogenic, hypertrophic, rRNA and osteoarthritis related gene expression.ConclusionWe demonstrate that snoRNA expression changes in cartilage ageing, and OA and in OA-like conditions, and when the expression of these snoRNAs is altered this affects chondrogenic and hypertrophic gene expression. Thus, we propose an additional dimension in the molecular mechanisms underlying cartilage ageing and OA through the dysregulation of snoRNAs.

Background: Osteoarthritis of the knee is characterized by progressive cartilage deterioration causing pain and function loss. Symptoms develop late with limited disease-modifying opportunities. Osteoarthritis is a major cause of immobility, with a higher prevalence above 60 years. This age-related increase in prevalence is further amplified by the female gender. Imaging and biochemical analyses for detection of osteoarthritis of the knee are expensive and labor-intensive. Continuous movement tracking could aid in detecting onset and/or worsening of symptoms.Methods: We used portable technology to investigate kinematic differences in female patients with knee osteoarthritis, weight-matched healthy female volunteers and obese female patients with osteoarthritis of the knee. Knee osteoarthritis was established radiographically and corroborated using magnetic resonance imaging.Findings: The total amount, type and level of activity did not differ significantly between groups. The temporal activity pattern during the day was however significantly different with a bimodal signature in healthy volunteers only. Sequence analyses revealed more time to recuperate after dynamic activity in both patient groups. Analysis of walking bouts revealed significant differences in stride interval dynamics, indicative of gait naturalness, only in healthy volunteers. Temporal activity, sequence and walking patterns were independent of body weight.Interpretation: We thus provide for the first-time evidence of temporal specific kinematic signatures in amount and quality of movement also in stride interval dynamics between people with and without osteoarthritis of the knee independent of body weight. These findings could allow early and non-intrusive diagnosis of osteoarthritis enabling concordant treatment.

A histological study of a structure between the posterior horn of the lateral meniscus and the anterior cruciate ligament.Bilateral fresh-frozen cadaveric knees of two male donors (age 71 and 76 years) with no history of prior knee injury were examined. All dissections were performed by one experienced orthopaedic surgeon. Haematoxylin and Eosin staining was used to reveal tissue morphology. Goldner trichrome staining was used to evaluate the connective tissue. S100 and PGP 9.5 labelling were used for immunohistochemical analysis.In all cadaveric knees, a structure between the posterior horn of the lateral meniscus and the anterior cruciate ligament was identified. Histological analysis confirmed the ligamentous nature of this structure. Furthermore, Golgi tendon organs were observed within the ligamentous structure.This is the first study showing the presence of mechanoreceptors within the ligamentous structure between the posterior horn of the lateral meniscus and the anterior cruciate ligament. The ligamentous structure could contribute to stability of the knee by providing proprioceptive input, while preservation of the ligamentous structure might ensure a better functional outcome after surgery.

The generation of cartilage from progenitor cells for the purpose of cartilage repair is often hampered by hypertrophic differentiation of the engineered cartilaginous tissue caused by endochondral ossification. Since a healthy cartilage matrix contains high amounts of Aggrecan and COMP, we hypothesized that their supplementation in the biogel used in the generation of subperiosteal cartilage mimics the composition of the cartilage extracellular matrix environment, with beneficial properties for the engineered cartilage. Supplementation of COMP or Aggrecan was studied in vitro during chondrogenic differentiation of rabbit periosteum cells and periosteum-derived chondrocytes. Low melting agarose was supplemented with bovine Aggrecan, human recombinant COMP or vehicle and was injected between the bone and periosteum at the upper medial side of the tibia of New Zealand white rabbits. Generated subperiosteal cartilage tissue was analyzed for weight, GAG and DNA content and ALP activity. Key markers of different phases of endochondral ossification were measured by RT-qPCR. For the in vitro experiments, no significant differences in chondrogenic marker expression were detected following COMP or Aggrecan supplementation, while in vivo favorable chondrogenic marker expression was detected. Gene expression levels of hypertrophic markers as well as ALP activity were significantly decreased in the Aggrecan and COMP supplemented conditions compared to controls. The wet weight and GAG content of the in vivo generated subperiosteal cartilage tissue was not significantly different between groups. Data demonstrate the potential of Aggrecan and COMP to favorably influence the subperiosteal microenvironment for the in vivo generation of cartilage for the optimization of cartilage regenerative approaches.

Patient-specific instrumentation (PSI) is a technique to plan and position the prosthesis components in unicompartmental knee arthroplasty (UKA) surgery. This study assesses whether the definitive component position in the frontal, sagittal and axial plane is according to the preoperative plan, based on the hypothesis that PSI is accurate. Twenty-six patients who had PSI Oxford UKA surgery were included prospectively. The component position in vivo was determined with a postoperative CT-scan and compared with the planned component position using MRI-based digital 3D imaging. Adjustments to the preoperative plan and implanted component sizes during surgery were recorded. Intraoperatively, no femoral adjustments were performed; 12 tibial re-resections were necessary. The median absolute deviation from the plan in degrees (range) in the frontal, sagittal and axial plane was 1.8A degrees (- 1.5A degrees-6.5A degrees), 2.0A degrees (- 6.5A degrees-8.0A degrees) and 1.0A degrees (- 1.5A degrees-5.0A degrees) for the femoral component, and 2.5A degrees (- 1.0A degrees-6.0A degrees), 3.0A degrees (- 1.0A degrees-5.0A degrees) and 5.0A degrees (- 6.5A degrees-12.5A degrees) for the tibial component. The femoral component is positioned 0.5 (- 1A degrees-2.5A degrees) mm more lateral and 0.8 (- 1.0A degrees-2.5A degrees) mm more anterior. The tibial component is positioned 2.0 (- 5.0-0.0) mm more lateral and 1.3 (- 3.0-6.0) mm more distal. The femoral and tibial default plans were changed four times (15.4%) and nine times (34.6%), respectively, before approval by the surgeon. PSI in Oxford UKA surgery is reliable and accurately translates the preoperative plan into the in vivo situation, except for the tibial rotational position. The preoperative planning is a crucial step in avoiding re-resections that can cause angular deviations in prosthesis position, especially in tibial component rotational position. It is advised to avoid re-resections and to consider this while planning the PSI procedure. Prospective comparative study Level II.

Previous studies have compared weight-bearing mechanical leg axis (MLA) measurements to non-weight-bearing measurement modalities. Most of these studies compared mean or median values and did not analyse within-person differences between measurements. This study evaluates the within-person agreement of MLA measurements between weight-bearing full-length radiographs (FLR) and non-weight-bearing measurement modalities (computer-assisted surgery (CAS) navigation or MRI).Two independent observers measured the MLA on pre- and postoperative weight-bearing FLR in 168 patients. These measurements were compared to non-weight-bearing measurements obtained by CAS navigation or MRI. Absolute differences in individual subjects were calculated to determine the agreement between measurement modalities. Linear regression was used to evaluate the possibility that other independent variables impact the differences in measurements.A difference was found in preoperative measurements between FLR and CAS navigation (mean of 2.5A degrees with limit of agreement (1.96 SD) of 6.4A degrees), as well as between FLR and MRI measurements (mean of 2.4A degrees with limit of agreement (1.96 SD) of 6.9A degrees). Postoperatively, the mean difference between MLA measured on FLR compared to CAS navigation was 1.5A degrees (limit of agreement (1.96 SD) of 4.6A degrees). Linear regression analysis showed that weight-bearing MLA measurements vary significantly from non-weight-bearing MLA measurements. Differences were more severe in patients with mediolateral instability (p = 0.010), age (p = 0.049) and ae3A degrees varus or valgus alignment (p = 0.008).The clinical importance of this study lies in the finding that there are within-person differences between weight-bearing and non-weight-bearing measurement modalities. This has implications for preoperative planning, performing total knee arthroplasty (TKA), and clinical follow-up after TKA surgery using CAS navigation or patient-specific instrumentation.III.

Background: The aim of this study was to compare the accuracy of the oscillating tip saw system (Precision Saw = PS) with the more conventional fully oscillating blade system (Sagittal Saw = SS) during computer-assisted total knee arthroplasty (CAS-TKA).Methods: A prospective, randomised, controlled trial included 58 consecutive patients who underwent primary CAS-TKA and were randomly assigned in the PS group or the SS group to compare the accuracy of both blades. The primary outcome was the difference between the intended cutting planes and the actual cutting planes in degrees () in two planes of both the femur and the tibia. The secondary outcome was total surgery time.Results: Tibia: In the W-plane no significant differences were registered for the mean absolute deviation (p = 0.28). The PS was more accurate in the AP-plane (p = 0.03). Femur: The PS showed significantly fewer mean absolute deviations in the W-plane (p = 0.03); however, the SS revealed better accuracy in the FE-plane (p = 0.04). The difference in the surgery time between the groups was not statistically significant (p = 0.45). Two outliers were measured using the SS, while seven outliers were detected using the PS.Conclusion: The Precision Saw is not proven to be overall more accurate than the Sagittal Saw. Significantly better accuracy was shown with the PS in the two cutting planes, with the exception of one cutting plane that favoured the SS. Greater number of outliers were found using the PS. (C) 2017 Elsevier B.V. All rights reserved.

Aims Knee joint distraction (KJD) is a relatively new, knee-joint preserving procedure with the goal of delaying total knee arthroplasty (TKA) in young and middle-aged patients. We present a randomised controlled trial comparing the two. Patients and Methods The 60 patients ≤ 65 years with end-stage knee osteoarthritis were randomised to either KJD (n = 20) or TKA (n = 40). Outcomes were assessed at baseline, three, six, nine, and 12 months. In the KJD group, the joint space width (JSW) was radiologically assessed, representing a surrogate marker of cartilage thickness. Results In total 56 patients completed their allocated treatment (TKA = 36, KJD = 20). All patient reported outcome measures improved significantly over one year (p < 0.02) in both groups. At one year, the TKA group showed a greater improvement in only one of the 16 patient-related outcome measures assessed (p = 0.034). Outcome Measures in Rheumatology-Osteoarthritis Research Society International clinical response was 83% after TKA and 80% after KJD. A total of 12 patients (60%) in the KJD group sustained pin track infections. In the KJD group both mean minimum (0.9 mm, standard deviation (sd) 1.1) and mean JSW (1.2 mm, sd 1.1) increased significantly (p = 0.004 and p = 0.0003). Conclusion In relatively young patients with end-stage knee osteoarthritis, KJD did not demonstrate inferiority of outcomes at one year when compared with TKA. However, there is a high incidence of pin track infection associated with KJD. Cite this article: Bone Joint J 2017;99-B:51–8.

Background: Genu recurvatum is a rare condition in children and adolescents. The origin can be osseous, ligamentous and mixed.Methods: We describe for the first time a family inclusive two brothers and their mother with hereditary bilateral genu recurvatum of unknown etiology. The possible underlying pathology and treatment are discussed.Results: The underlying pathology of the early closure of the apophysis of the tibial tuberosity remained unclear. The mother was never treated, one of the brothers received a tibial osteotomy as a young adult. Both patients developed end-stage osteoarthritis of both knees which was successfully treated by a bilateral computer-navigated TKA.At seven to eight years after implantation in the older brother (left and right knee, respectively) and three to four years after implantation in the younger brother (right and left knee, respectively), the Visual Analogue Scale (VAS) pain score on a 0 to 100 scale was 0 of both brothers, the EQ-5D health status was 80 (scale of 0 to 100), the satisfaction was 10 (scale of 10) of both brothers.The Knee Injury and Osteoarthritis Outcome Score (KOOS) function of the younger brother of 75 (scale 0 to 100) and of the older brother 100. The KOOS sport of the younger brother was 10 (scale 0 to 100), whereas that of the older brother 85.Conclusions: Hereditary bilateral genu recurvatum with end-stage osteoarthritis can be successfully treated with computer-navigated TKAs; however, impingement of the patella on the proximal tibia and the position of the tibial keel are of concern. (C) 2016 Elsevier B.V. All rights reserved.

Background Historically it has been suggested that noise-induced hearing loss (NIHL) affects approximately 50% of the orthopedic surgery personnel. This noise may be partially caused by the use of powered saw systems that are used to make the bone cuts. The first goal was to quantify and compare the noise emission of these different saw systems during total knee arthroplasty (TKA) surgery. A second goal was to estimate the occupational NIHL risk for the orthopedic surgery personnel in TKA surgery by quantifying the total daily noise emission spectrum during TKA surgery and to compare this to the Dutch Occupational Health Organization guidelines. Methods A conventional sagittal oscillating blade system with a full oscillating blade and 2 newer oscillating tip saw systems (handpiece and blade) were compared. Noise level measurements during TKA surgery were performed during cutting and hammering, additionally surgery noise profiles were made. Results The noise level was significantly lower for the oscillating tip saw systems compared to the conventional saw system, but all were in a range that can cause NIHL. The conventional system handpiece produced a considerable higher noise level compared to oscillating tip handpiece. Conclusion NIHL is an underestimated problem in the orthopedic surgery. Solutions for decreasing the risk of hearing loss should be considered. The use of oscillating tip saw systems have a reduced noise emission in comparison with the conventional saw system. The use of these newer systems might be a first step in decreasing hearing loss among the orthopedic surgery personnel.

Skeletal muscle plasticity is reflected by a dynamic balance between protein synthesis and breakdown, with basal muscle tissue protein synthesis rates ranging between 0.02 and 0.09%/h. Though it is evident that other musculoskeletal tissues should also express some level of plasticity, data on protein synthesis rates of most of these tissues in vivo in humans is limited. Six otherwise healthy patients (62±3 y), scheduled to undergo unilateral total knee arthroplasty, were subjected to primed continuous intravenous infusions with L-[ring-13C6]-Phenylalanine throughout the surgical procedure. Tissue samples obtained during surgery included muscle, tendon, cruciate ligaments, cartilage, bone, menisci, fat, and synovium. Tissue-specific fractional protein synthesis rates (%/h) were assessed by measuring the incorporation of L-[ring-13C6]-Phenylalanine in tissue protein and were compared with muscle tissue protein synthesis rates using a paired t test. Tendon, bone, cartilage, Hoffa's fat pad, anterior and posterior cruciate ligament, and menisci tissue protein synthesis rates averaged 0.06±0.01, 0.03±0.01, 0.04±0.01, 0.11±0.03, 0.07±0.02, 0.04±0.01, and 0.04±0.01%/h, respectively, and did not significantly differ from skeletal muscle protein synthesis rates (0.04±0.01%/h; P>0.05). Synovium derived protein (0.13±0.03%/h) and intercondylar notch bone tissue protein synthesis rates (0.03±0.01%/h) were respectively higher and lower compared to skeletal muscle protein synthesis rates (P

OBJECTIVE: To assess the efficacy of a 12-week aquatic cycling training program for improving knee pain and physical functioning in patients with knee osteoarthritis.DESIGN: Two-arm, single-blind, parallel-group randomized controlled trial.SETTINGS: OA outpatient clinic of the Maastricht University Medical Center.PARTICIPANTS: Patients (N=111, 50-70 years old) with unilateral mild to moderate knee OA.INTERVENTIONS: Participants (AC, n=55) received aquatic cycling sessions of 45 min twice-weekly. Each session combined up-right seated cycling with out-of-saddle positions and exercises for the upper and lower body. The usual care group (UC, n=47) continued with usual care and was offered twelve aquatic cycling sessions in a local swimming pool after their trial participation.MAIN OUTCOME MEASURES: The Knee Injury and Osteoarthritis Outcome Score (KOOS) on knee pain and physical function was assessed at baseline, post-intervention and 24-weeks follow-up. Multilevel (mixed regression) analysis examined the effects.RESULTS: Average attendance rate for the aquatic cycling sessions was 80%. Statistically significant differences at post-intervention and follow-up were found for knee pain (UC pretest 57.89 ±15.26, posttest 55.90 ±18.04, follow-up 57.24 ±19.16; AC pretest 56.96 ±12.96, posttest 63.55 ±15.33, follow-up 64.35 ±17.26, Estimate 8.16, SE 3.27, 95% CI 1.67 to 14.64; ES = 0.50) and physical functioning (UC pretest 66.32 ±16.28, posttest 66.80 ±19.04, follow-up 65.42 ±17.98; AC pretest 61.89 ±17.151, posttest 70.14 ±17.52, follow-up 69.00 ±16.84, Estimate 7.16, SE 3.19, 95% CI 0.83-13.49, ES = 0.43) in favour of the aquatic group.CONCLUSION: The results suggest that a 12-week aquatic cycling training programme improves self-reported knee pain and physical functioning in patients with mild to moderate knee OA compared to usual care.

Purpose Observational studies showed inverse associations between milk consumption and knee osteoarthritis (knee OA). There is lack of information on the role of specific dairy product categories. We explored the association between dairy consumption and the presence of knee osteoarthritis in 3010 individuals aged 40-75 years participating in The Maastricht Study.Methods The presence of knee OA was defined according to a slightly modified version of the American College of Rheumatology (ACR) clinical classification criteria. Data on dairy consumption were appraised by a 253-item FFQ covering 47 dairy products with categorization on fat content, fermentation or dairy type. Multivariable logistic regression analyses were performed to estimate odd ratios (ORs) and 95% confidence intervals (95%CI), while correcting for relevant factors.Results 427 (14%) participants were classified as having knee OA. Significant inverse associations were observed between the presence of knee OA and intake of full-fat dairy and Dutch, primarily semi-hard, cheese, with OR for the highest compared to the lowest tertile of intake of 0.68 (95%CI 0.50-0.92) for full-fat dairy, and 0.75 (95%CI 0.56-0.99) for Dutch cheese. No significant associations were found for other dairy product categories.Conclusion In this Dutch population, higher intake of full-fat dairy and Dutch cheese, but not milk, was cross-sectionally associated with the lower presence of knee OA. Prospective studies need to assess the relationship between dairy consumption, and in particular semi-hard cheeses, with incident knee OA.

Focal knee resurfacing implants (FKRIs) are intended to treat cartilage defects in middle‐aged patients. Most FKRIs are metal‐based, which hampers follow‐up of the joint using magnetic resonance imaging and potentially leads to damage of the opposing cartilage. The purpose of this study was to develop a nondegradable thermoplastic polyurethane (TPU) FKRI and investigate its osseointegration. Different surface roughness modifications and biphasic calcium phosphate (BCP) coating densities were first tested in vitro on TPU discs. The in vivo osseointegration of BCP‐coated TPU implants was subsequently compared to uncoated TPU implants and the titanium bottom layer of metal control implants in a caprine model. Implants were implanted bilaterally in stifle joints and animals were followed for 12 weeks, after which the bone‐to‐implant contact area (BIC) was assessed. Additionally, 18F‐sodium‐fluoride (18F‐NaF) positron emission tomography PET/CT‐scans were obtained at 3 and 12 weeks to visualize the bone metabolism over time. The BIC was significantly higher for the BCP‐coated TPU implants compared to the uncoated TPU implants (p = .03), and did not significantly differ from titanium (p = .68). Similar 18F‐NaF tracer uptake patterns were observed between 3 and 12 weeks for the BCP‐coated TPU and titanium implants, but not for the uncoated implants. TPU FKRIs with surface modifications could provide the answer to the drawbacks of metal FKRIs.

To assess human articular cartilage tissue functionality by serial multiparametric quantitative MRI (qMRI) mapping as a function of histological degeneration. Forty-nine cartilage samples obtained during total knee replacement surgeries were placed in a standardized artificial knee joint within an MRI-compatible compressive loading device and imaged in situ and at three loading positions, i.e. unloaded, at 2.5 mm displacement (20% body weight [BW]) and at 5 mm displacement (110% BW). Using a clinical 3.0 T MRI system (Achieva, Philips), serial T1, T1ρ, T2 and T2* maps were generated for each sample and loading position. Histology (Mankin scoring) and biomechanics (Young’s modulus) served as references. Samples were dichotomized as intact (int, n = 27) or early degenerative (deg, n = 22) based on histology and analyzed using repeated-measures ANOVA and unpaired Student’s t-tests after log-transformation. For T1ρ, T2 and T2*, significant loading-induced differences were found in deg (in contrast to int) samples, while for T1 significant decreases in all zones were observed, irrespective of degeneration. In conclusion, cartilage functionality may be visualized using serial qMRI parameter mapping and the response-to-loading patterns are associated with histological degeneration. Hence, loading-induced changes in qMRI parameter maps provide promising surrogate parameters of tissue functionality and status in health and disease.

During standard expansion culture (i.e., plasma osmolarity, 280 mOsm) human articular chondrocytes dedifferentiate, making them inappropriate for autologous chondrocyte implantation to treat cartilage defects. Increasing the osmolarity of culture media to physiological osmolarity levels of cartilage (i.e., 380 mOsm), increases collagen type II (COL2A1) expression of human articular chondrocytes in vitro, but the underlying molecular mechanism is not fully understood. We hypothesized that TGF-&beta, superfamily signaling may drive expression of COL2A1 under physiological osmolarity culture conditions. Human articular chondrocytes were cultured in cytokine-free medium of 280 or 380 mOsm with or without siRNA mediated TGF-&beta, 2 knockdown (RNAi). Expression of TGF-&beta, isoforms, and collagen type II was evaluated by RT-qPCR and immunoblotting. TGF-&beta, 2 protein secretion was evaluated using ELISA and TGF-&beta, bioactivity was determined using an established reporter assay. Involvement of BMP signaling was investigated by culturing human articular chondrocytes in the presence or absence of BMP inhibitor dorsomorphin and BMP bioactivity was determined using an established reporter assay. Physiological cartilage osmolarity (i.e., physosmolarity) most prominently increased TGF-&beta, 2 mRNA expression and protein secretion as well as TGF-&beta, bioactivity. Upon TGF-&beta, 2 isoform-specific knockdown, gene expression of chondrocyte marker COL2A1 was induced. TGF-&beta, 2 RNAi under physosmolarity enhanced TGF-&beta, bioactivity. BMP bioactivity increased upon physosmotic treatment, but was not related to TGF-&beta, 2 RNAi. In contrast, dorsomorphin inhibited COL2A1 mRNA expression in human articular chondrocytes independent of the osmotic condition. Our data suggest a role for TGF-&beta, superfamily member signaling in physosmolarity-induced mRNA expression of collagen type II. As physosmotic conditions favor the expression of COL2A1 independent of our manipulations, contribution of other metabolic, post-transcriptional or epigenetic factors cannot be excluded in the underlying complex and interdependent regulation of marker gene expression. Dissecting these molecular mechanisms holds potential to further improve future cell-based chondral repair strategies.

Introduction: Meniscus loss is a known cause for medial compartment joint pain related to knee osteoarthritis (KOA). The cartilage in knee joints of KOA patients degenerates over time, resulting in accumulative complaints and reduced quality of life. When the osteoarthritis progresses knee arthroplasty is often the eventual treatment once they have reached the eligible age. In case of low grade KOA and an absent meniscus, the orthopedic surgeon currently has no established surgical procedure at hand to restore the knee mechanics and provide pain relief. Methods: A durable medial meniscus prosthesis has been developed to overcome this treatment gap. This anatomically shaped polymer prosthesis is based on a decade of pre-clinical work at the Radboudumc. The Trammpolin meniscus prosthesis is currently being evaluated in a First in Human clinical trial in three orthopedic centers in the Netherlands. The first results and next steps will be shared in this presentation.