The BMP7-Derived Peptide p[63-82] Reduces Cartilage Degeneration in the Rat ACLT-pMMx Model for Posttraumatic Osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is characterized by articular cartilage erosion, pathological subchondral bone changes, and signs of synovial inflammation and pain. We previously identified p[63-82], a bone morphogenetic protein 7 (BMP7)-derived bioactive peptide that attenuates structural cartilage degeneration in the rat medial meniscal tear-model for posttraumatic OA. This study aimed to evaluate the cartilage erosion-attenuating activity of p[63-82] in a different preclinical model for OA (anterior cruciate ligament transection-partial medial meniscectomy [anterior cruciate ligament transection (ACLT)-pMMx]). The disease-modifying action of the p[63-82] was followed-up in this model for 5 and 10 weeks. DESIGN: Skeletally mature male Lewis rats underwent ACLT-pMMx surgery. Rats received weekly intra-articular injections with either saline or 500 ng p[63-82]. Five and 10 weeks postsurgery, rats were sacrificed, and subchondral bone characteristics were determined using microcomputed tomography (µCT). Histopathological evaluation of cartilage degradation and Osteoarthritis Research Society International (OARSI)-scoring was performed following Safranin-O/Fast Green staining. Pain-related behavior was measured by incapacitance testing and footprint analysis. RESULTS: Histopathological evaluation at 5 and 10 weeks postsurgery showed reduced cartilage degeneration and a significantly reduced OARSI score, whereas no significant changes in subchondral bone characteristics were found in the p[63-82]-treated rats compared to the saline-treated rats. ACLT-pMMx-induced imbalance of static weightbearing capacity in the p[63-82] group was significantly improved compared to the saline-treated rats at weeks 5 postsurgery. Footprint analysis scores in the p[63-82]-treated rats demonstrated improvement at week 10 postsurgery. CONCLUSIONS: Weekly intra-articular injections of p[63-82] in the rat ACLT-pMMx posttraumatic OA model resulted in reduced degenerative cartilage changes and induced functional improvement in static weightbearing capacity during follow-up.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) reveals potential lipid markers between infrapatellar fat pad biopsies of osteoarthritis and cartilage defect patients.

The incidence of osteoarthritis (OA) has been expected to increase due to an aging population, as well as an increased incidence of intra-articular (osteo-) chondral damage. Lipids have already been shown to be involved in the inflammatory process of OA. This study aims at revealing region-specific lipid profiles of the infrapatellar fat pad (IPFP) of OA or cartilage defect patients by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which could be used as biomarkers for early OA detection. A higher presence of phospholipids was found in OA patients compared with cartilage defect patients. In addition, a higher abundance of ether-linked phosphatidylethanolamines (PE O-s) containing arachidonic acid was specifically found in OA patients compared with cartilage defect patients. These lipids were mainly found in the connective tissue of the IPFP. Specific lipid species were associated to OA patients compared with cartilage defect patients. PE O-s have been suggested as possible biomarkers for OA. As these were found more abundantly in the connective tissue, the IPFP's intra-tissue heterogeneity might play an important role in biomarker discovery, implying that the amount of fibrous tissue is associated with OA.

Joint distraction using a purpose-built device for knee osteoarthritis: a prospective 2-year follow-up.

OBJECTIVE: Knee distraction treatment for end-stage osteoarthritis successfully postpones arthroplasty for years. Studies performed thus far used general intended use, patient-personalised or custom-made devices. In this study, for the first time, a device specifically designed for knee distraction is evaluated. DESIGN: 65 patients (≤65 years) with end-stage knee osteoarthritis indicated for arthroplasty received knee distraction. Before, 1-year and 2-year post-treatment, questionnaires were filled out and knee radiographs made. Adverse events and self-reported pain medication were registered. RESULTS: Forty-nine patients completed 2-year follow-up: one patient did not complete treatment, three patients received arthroplasty in the first and four patients in the second year follow-up. Eight patients were lost to follow-up in the second year. The total Western Ontario and McMaster Universities Osteoarthritis Index score showed a clinically relevant improvement at 1 and 2 years (+26 and +24 points), as did all subscales (all p<0.001). The minimum radiographic joint space width improved over 1 (+0.5 mm; p<0.001) and 2 (+0.4 mm; p=0.015) years, as did the physical Short-Form 36 (+10 points; p<0.001). The most common adverse event was pin tract infection, experienced by 66% of patients, in 88% successfully treated with oral antibiotics. In two cases, hospitalisation and/or intravenous antibiotics were needed. Eight patients experienced device-related complications. None of the complications influenced 2-year outcomes. Before treatment, 42% of patients used pain medication, which had nearly been halved 1 (23%; p=0.02) and 2 years (29%; p=0.27) post-treatment. CONCLUSIONS: Patients treated with a general applicable, for knee distraction purpose-built device showed, despite adverse events, significant clinical and structural improvement over 2 years. TRIAL REGISTRATION NUMBER: NL7986.

High degree of consensus amongst an expert panel regarding focal resurfacing of chondral and osteochondral lesions of the femur with mini-implants.

INTRODUCTION: The rationale for the use of mini-implants for partial resurfacing in the treatment of femoral chondral and osteochondral lesions is still under debate. The evidence supporting best practise guidelines is based on studies with low-level evidence. A consensus group of experts was convened to collaboratively advance towards consensus opinions regarding the best available evidence. The purpose of this article is to report the resulting consensus statements. METHODS: Twenty-five experts participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted via an online survey of two rounds, for initial agreement and comments on the proposed statements. An in-person meeting between the panellists was organised during the 2022 ESSKA congress to further discuss and debate each of the statements. A final agreement was made via a final online survey a few days later. The strength of consensus was characterised as: consensus, 51-74% agreement; strong consensus, 75-99% agreement; unanimous, 100% agreement. RESULTS: Statements were developed in the fields of patient assessment and indications, surgical considerations and postoperative care. Between the 25 statements that were discussed by this working group, 18 achieved unanimous, whilst 7 strong consensus. CONCLUSION: The consensus statements, derived from experts in the field, represent guidelines to assist clinicians in decision-making for the appropriate use of mini-implants for partial resurfacing in the treatment of femoral chondral and osteochondral lesions. LEVEL OF EVIDENCE: Level V.

Mimicking the Graded Wavy Structure of the Anterior Cruciate Ligament.

Anterior cruciate ligament (ACL) is the connective tissue providing mechanical stability to the knee joint. ACL reconstruction upon rupture remains a clinical challenge due to the high mechanical properties required for proper functioning. ACL owes its outstanding mechanical properties to the arrangement of the extracellular matrix (ECM) and to the cells with distinct phenotypes present along the length of the tissue. Tissue regeneration appears as an ideal alternative. In this study, a tri-phasic fibrous scaffold that mimics the structure of collagen in the native ECM is developed, presenting a wavy intermediate zone and two aligned uncurled extremes. The mechanical properties of the wavy scaffolds present a toe region, characteristic of the native ACL, and an extended yield and ultimate strain compared to aligned scaffolds. The presentation of a wavy fiber arrangement affects cell organization and the deposition of a specific ECM characteristic of fibrocartilage. Cells cultured in wavy scaffolds grow in aggregates, deposit an abundant ECM rich in fibronectin and collagen II, and express higher amounts of collagen II, X, and tenomodulin as compared to aligned scaffolds. In vivo implantation in rabbits shows a high cellular infiltration and the formation of an oriented ECM compared to aligned scaffolds.

Cost-effectiveness of a new ACI technique for the treatment of articular cartilage defects of the knee compared to regularly used ACI technique and microfracture.

AIMS: For patients with cartilage defects of the knee, a new biocompatible and in situ cross-linkable albumin-hyaluronan-based hydrogel has been developed for matrix-associated autologous chondrocyte implantation (M-ACI) - NOVOCART Inject plus (Ninject; TETEC AG, Reutlingen, Germany). We aimed to estimate the potential cost-effectiveness of NInject, that is not available on the market, yet compared to spheroids of human autologous matrix-associated chondrocytes (Spherox; CO.DON GmbH, Leipzig, Germany) and microfracture. MATERIALS AND METHODS: An early Markov model was developed to estimate the cost-effectiveness in the United Kingdom (UK) from the payer perspective. Transition probabilities, response rates, utility values and costs were derived from literature. Since NInject has not yet been launched and no prices are available, its costs were assumed equal to those of Spherox. Cycle length was set at one year and the time horizon chosen was notional patients' remaining lifetime. Model robustness was evaluated with deterministic and probabilistic sensitivity analyses (DSA; PSA) and value of information analysis (VOIA). The Markov model was built using TreeAge Pro Healthcare. RESULTS: NInject was cost-effective compared to microfracture (ICER: £5,147) while Spherox was extendedly dominated. In sensitivity analyses, the ICER exceeded conventional WTP threshold of £20,000 only when the utility value after successful first treatment with NInject was decreased by 20% (ICER: £69,620). PSA corroborated the cost-effectiveness findings of NInject, compared to both alternatives, with probabilities of 60% of NInject undercutting the aforementioned WTP threshold and being the most cost-effective alternative. The VOIA revealed that obtaining additional evidence on the new technology will likely not be cost-effective for the UK National Health Service. LIMITATIONS AND CONCLUSION: This early Markov model showed that NInject is cost-effective for the treatment of articular cartilage defects in the knee, compared to Spherox and microfracture. However, as the final price of NInject has yet to be determined, the cost-effectiveness analysis performed in this study is provisional, assuming equal prices for NInject and Spherox.

Current clinical practice of knee osteotomy in the Netherlands.

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 investigate 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 realignment osteotomies around the knee. All the 60 responders (100%) perform high tibial osteotomies 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.

Prognostic Factors for the Clinical Outcome after Microfracture Treatment of Chondral and Osteochondral Defects in the Knee Joint: A Systematic Review.

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.

Sample preparation for lipid analysis of intra-articular adipose tissue by using matrix-assisted laser desorption/ionization imaging.

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.

The preferred technique for knee synovium biopsy and synovial fluid arthrocentesis.

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.

Evaluation of the Anti-Inflammatory and Chondroprotective Effect of Celecoxib on Cartilage Ex Vivo and in a Rat Osteoarthritis Model.

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.

Surface texture analysis of different focal knee resurfacing implants after 6 and 12 months in vivo in a goat model.

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.

A Systematic Review of Focal Cartilage Defect Treatments in Middle-Aged Versus Younger Patients.

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.

A White Paper on Collagen Hydrolyzates and Ultrahydrolyzates: Potential Supplements to Support Joint Health in Osteoarthritis?

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. 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.

Mass Spectrometry-based Biomarkers for Knee Osteoarthritis: A Systematic Review.

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.

Discovery of bone morphogenetic protein 7-derived peptide sequences that attenuate the human osteoarthritic chondrocyte phenotype.

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.

Heterogeneity of Lipid and Protein Cartilage Profiles Associated with Human Osteoarthritis with or without Type 2 Diabetes Mellitus.

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.

Knee Joint Distraction Compared with High Tibial Osteotomy and Total Knee Arthroplasty: Two-Year Clinical, Radiographic, and Biochemical Marker Outcomes of Two Randomized Controlled Trials.

OBJECTIVE: Both, knee joint distraction (KJD) and high tibial osteotomy (HTO) are joint-preserving surgeries that postpone total knee arthroplasty (TKA) in younger osteoarthritis (OA) patients. Here we evaluate the 2-year follow-up of KJD versus TKA and KJD versus HTO in 2 noninferiority studies. DESIGN: Knee OA patients indicated for TKA were randomized to KJD (n = 20; KJDTKA) or TKA (n = 40). Medial compartmental knee OA patients considered for HTO were randomized to KJD (n = 23; KJDHTO) or HTO (n = 46). Patient-reported outcome measures were assessed over 2 years of follow-up. The radiographic joint space width (JSW) was measured yearly. In the KJD groups, serum-PIIANP and urinary-CTXII levels were measured as collagen type-II synthesis and breakdown markers. It was hypothesized that there was no clinically important difference in the primary outcome, the total WOMAC, when comparing KJD with HTO and with TKA. RESULTS: Both trials were completed, with 114 patients (19 KJDTKA; 34 TKA; 20 KJDHTO; 41 HTO) available for 2-year analyses. At 2 years, the total WOMAC score (KJDTKA: +30.4 [95% CI 23.0-37.9] points; TKA: +42.4 [95% CI 38.1-46.8]; KJDHTO: +21.6 [95% CI 13.8-29.4]; HTO: +29.2 [95% CI 23.6-34.8]; all: P < 0.05) and radiographic minimum JSW (KJDTKA: +0.9 [95% CI 0.2-1.6] mm; KJDHTO: +0.9 [95% CI 0.5-1.4]; HTO: +0.6 [95% CI 0.3-0.9]; all: P < 0.05) were still increased for all groups. The net collagen type-II synthesis 2 years after KJD was increased (P < 0.05). Half of KJD patients experienced pin tract infections, successfully treated with oral antibiotics. CONCLUSIONS: Sustained improvement of clinical benefit and (hyaline) cartilage thickness increase after KJD is demonstrated. KJD was clinically noninferior to HTO and TKA in the primary outcome.

Mechanoreceptors observed in a ligamentous structure between the posterior horn of the lateral meniscus and the anterior cruciate ligament.

PURPOSE: A histological study of a structure between the 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.