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Bone and cartilage diseases are often associated with trauma and senescence, manifested as pain and limited mobility. The repair of bone and cartilage lesion by mesenchymal stem cells is regulated by various transcription factors. WW domain-containing protein 1 (WWP1) and WW domain-containing protein 2 (WWP2) are named for WW domain which recognizes PPXY (phono Ser Pro and Pro Arg) motifs of substrate. WWP1and WWP2 are prominent components of the homologous to the E6-AP carboxyl terminus (HECT) subfamily, a group of the ubiquitin ligase. Recently, some studies have found that WWP1 and WWP2 play an important role in the pathogenesis of bone and cartilage diseases and regulate the level and the transactivation of various transcription factors through ubiquitination. Therefore, this review summarizes the distribution and effects of WWP1 and WWP2 in the development of bone and cartilage, discusses the potential mechanism and therapeutic drugs in bone and cartilage diseases such as osteoarthritis, fracture, and osteoporosis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To explain the relationship between cartilage erosion and medial patellar luxation (MPL) and to identify risk factors in dogs., Methods: A retrospective review was conducted on 90 dogs (103 stifles) surgically treated for MPL between January 2006 and March 2024. Data collected included signalment, side of operated stifle, patellar luxation grade, symptom duration, and lameness score. Cartilage erosion was evaluated for extent and location on the patella and femoral trochlea. Statistical analyses were conducted to identify risk factors., Results: The prevalence of cartilage erosion of the patella and femoral trochlea was 47.6% (49/103) and 54.4% (56/103), respectively, increasing with a higher grade of patellar luxation. Lesions were most prevalent in the distolateral patella and proximomedial trochlea, with generalized lesions more prevalent in grade IV. The extent of both lesions was significantly associated with age, patellar luxation grade, and symptom duration, while body weight significantly correlated only with the cartilage erosion of the patella. No significant correlation was observed with sex, side of operated stifle, or lameness score., Conclusions: Many patients with MPL exhibited cartilage erosion in the patellofemoral joint, likely due to biomechanical mechanisms. Surgery can be indicated for patients with MPL, as it may prevent cartilage erosion while improving patellofemoral alignment and gait. When selecting surgical candidates, it is important to consider risk factors, such as patellar luxation grade, body weight, age, and symptom duration., Clinical Relevance: Early surgical treatment is recommended, especially for dogs with higher body weight and higher grade of MPL, to prevent cartilage erosion and secondary osteoarthritis.

Auricular chondritis of unknown cause was suspected in a 10-year-old male Bolognese dog with a five-month history of painful bilateral nodular and ulcerative pyogranulomatous dermatitis of the pinnae with putative auricular cartilage destruction. Pain and lesions resolved with immunosuppressive doses of prednisolone, yet the condition resulted in deformity of both pinnae and external canals., (© 2024 ESVD and ACVD.)

Background: To explore and compare the values of 3.0T magnetic resonance imaging (MRI) T2 mapping in evaluating the degree of acetabular cartilage degeneration in hip replacement surgery., Methods: A total of 26 elderly patients with femoral neck fractures who were scanned in 3.0T MRI T2 mapping quantification technique were included. Basing on MRI images, the degree of acetabular cartilage degeneration was classified into Grade 0, 1, 2, 3 and 4, according to the International Cartilage Repair Society (ICRS) scores. In addition, 8 healthy volunteers were included for control group., Results: By comparison with health population, T2 relaxation values in the anterior, superior, and posterior regions of acetabular cartilage in patients with femoral neck fracture were obviously increased (P < 0.001). Among the patients with femoral neck fractures, there were 16 hip joint with Grade 1-2 (mild degeneration subgroup) and 10 hip joints with Grade 3-4 (severe degeneration subgroup), accounting for 61.54% and 38.46%, respectively. Additionally, T2 relaxation values in the anterior and superior bands of articular cartilage were positively related to the MRI-based grading (P < 0.05); while there was no significant difference of T2 relaxation values in the posterior areas of articular cartilage between severe degeneration subgroup and mild degeneration subgroup (P > 0.05). Importantly, acetabular cartilage degeneration can be detected through signal changes of T2 mapping pseudo-color images., Conclusion: 3.0T MRI T2 mapping technology can be used to determine the degree of acetabular cartilage degeneration, which can effectively monitor the disease course., (© 2024. The Author(s).)

Objectives: In this study, we aimed to compare conventional and T1-weighted volumetric magnetic resonance arthrography (MRA) in the diagnosis and grading of glenoid cartilage defects that accompany labral pathologies., Materials and Methods: A total of 79 patients who were prediagnosed with labrum pathologies based on shoulder magnetic resonance imaging (MRI) had MRA and CTA between December 2021 and May 2022. CTA was regarded as reference standard. CTA images were examined by a radiologist experienced in musculoskeletal radiology, and MRA images were examined by two radiologists independently to determine presence, grade, and localization of any glenoid cartilage defect, if present. Sensitivity, specificity, and accuracy were calculated separately for conventional and T1-weighted volumetric MRA. In addition, at the last stage, two observers examined all MRAs together, and the presence of a cartilage defect was decided by consensus, and the overall sensitivity, specificity, and accuracy were calculated., Results: Cartilage defect was detected on CTAs of 48 (60.75%) cases of among 79 patients with labrum pathology. The sensitivity, specificity, and accuracy of conventional MRA for two examiners were 17-19%, 100-100%, and 49-51%, respectively, while those values were 67-65%, 92-97%, and 84-77%, respectively, for T1-weighted volumetric MRA. Inter-examiner agreement was excellent for diagnosis of cartilage defects on all MRAs. The overall sensitivity, specificity, and accuracy for detection of glenoid cartilage lesions by MRA were 69%, 97%, and 80%, respectively., Conclusion: T1-weighted volumetric MRA seems to demonstrate cartilage defects accompanied with labrum pathologies accurately with high sensitivity, specificity, and excellent inter-examiner agreement., (© 2023. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Objective: The decision on whether or not and how to treat a local cartilage defect is still made intraoperatively based on the visual presentation of the cartilage and findings from indentations with an arthroscopic probe. The treatment decision is then usually based on grading according to established classifications systems, which, therefore, need to have high reliability and accuracy. The aim of the present study was to evaluate the reliability and accuracy of the Outerbridge classification in staging cartilage defects., Methods: We performed an observer arthroscopic study using the Outerbridge classification on seven fresh-frozen human cadaveric knees, which collectively exhibited nine cartilage defects. To evaluate accuracy, defect severity was verified through histological examination. Interrater and intrarater reliabilites were calculated using Cohen's kappa and the intra-class correlation coefficient (ICC 3.1)., Results: The interrater and intrarater reliability for the Outerbridge classification ranged from poor to substantial, with 0.24 ≤ κ ≤ 0.70 and κ = 0.55 to κ = 0.66, respectively. The accuracy evaluated by comparison with the histological examination was 63% overall. The erroneous evaluations were, however, still often at the discrimination of grade 2 and 3. We did not find any relationship between higher experience and accuracy or intraobserver reliability. Taken together, these results encourage surgeons to further use diagnostic arthroscopy for evaluating cartilage lesions. Nevertheless, especially in grade 2 and 3, deviations from the histology were observed. This is, however, the point where a decision is made on whether to surgically address the defect or not., Conclusion: Diagnostic arthroscopy is the standard for cartilage lesion assessment, yet interobserver reliability is fair to substantial. Caution is warranted in interpreting varied observer results. The accuracy of the "simpler" Outerbridge classification is insufficient compared to histological examinations, highlighting the need for improved techniques in guideline-based intraoperative decision-making., (© 2024 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Nasal obstruction is a commonly reported issue in the Otorhinolaryngology Outpatient Department. In this case, an early adolescent boy with a long-standing problem of right-sided nasal obstruction since childhood sought consultation. Diagnostic nasal endoscopy revealed a deviation of the nasal septum to the left, coupled with right inferior turbinate hypertrophy, all overlying healthy mucosa. A CT scan of the nose and paranasal sinuses further identified a bony hyperdense lesion with ground glass attenuation, confined to the right inferior turbinate. Subsequent biopsy confirmed juvenile trabecular ossifying fibroma (JTOF). The patient underwent endoscopic right medial maxillectomy, and the final histology affirmed the diagnosis of JTOF., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Magnetic resonance imaging (MRI) is the clinical method of choice for cartilage imaging in the context of degenerative and nondegenerative joint diseases. The MRI-based definitions of osteoarthritis rely on the detection of osteophytes, cartilage pathologies, bone marrow edema and meniscal lesions but currently a scientific consensus is lacking. In the clinical routine proton density-weighted, fat-suppressed 2D turbo spin echo sequences with echo times of 30-40 ms are predominantly used, which are sufficiently sensitive and specific for the assessment of cartilage. The additionally acquired T1-weighted sequences are primarily used for evaluating other intra-articular and periarticular structures. Diagnostically relevant artifacts include magic angle and chemical shift artifacts, which can lead to artificial signal enhancement in cartilage or incorrect representations of the subchondral lamina and its thickness. Although scientifically validated, high-resolution 3D gradient echo sequences (for cartilage segmentation) and compositional MR sequences (for quantification of physical tissue parameters) are currently reserved for scientific research questions. The future integration of artificial intelligence techniques in areas such as image reconstruction (to reduce scan times while maintaining image quality), image analysis (for automated identification of cartilage defects), and image postprocessing (for automated segmentation of cartilage in terms of volume and thickness) will significantly improve the diagnostic workflow and advance the field further., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objective: To assess the applicability of a semiquantitative index for symptomatic minor instability of the lateral elbow (SMILE)., Materials and Methods: CT arthrograms of consecutive patients with lateral elbow pain who underwent ultrasound-guided CT arthrography at our orthopedic center between April 2019 and May 2022 were included. Images were acquired at 100 kVp and 80 mAs. An expert radiologist (R1) and a radiology resident (R2) retrospectively performed an independent, blinded evaluation of the arthrograms to assess the presence of imaging findings suggestive of elbow instability. The SMILE index (0-8) was obtained adding (I) radial head chondromalacia (0 - 1); (II) humeral capitellum chondromalacia (0 - 1); (III) humeral trochlear ridge chondromalacia (0 - 1); (IV) annular ligament laxity (0 - 2); (V) synovial thickening (0 - 1); (VI) humeroradial joint asymmetry (0 - 1); and (VII) capsular tear (0 - 1). R1 repeated the assessment after 14 days. Cohen's weighted κ statistic and raw concordance were used to appraise reproducibility., Results: Eighty patients (median age 49 years, interquartile range 40-53 years, 49, 61% males) underwent CT arthrography at our center, and 10 (12%) of them underwent bilateral elbow examination, leading to 90 included CT arthrograms. Median SMILE index was 4 (IQR: 2-5) for R1, 4 (IQR: 2-5) for R2, and 4 (IQR: 2-5) for the second assessment by R1. Intra-reader agreement was excellent (κ = 0.94, concordance 87%), while inter-reader agreement was substantial (κ = 0.75, concordance 67%)., Conclusion: The proposed SMILE index showed good reproducibility; further studies are warranted to correlate our index with clinical and surgical data., Clinical Relevance Statement: Our scoring system allows a standardized evaluation of patients with lateral elbow pain and instability suitable for application into clinical practice, complementing the orthopedic surgeon's clinical diagnosis with imaging findings that may aid treatment choices., Key Points: • Lateral elbow pain is often interpreted clinically as lateral epicondylitis, but it can also encompass intra-articular pathology. • The proposed arthrographic index allows comprehensive quantification of lateral elbow pathology with good reproducibility and application times. • Our index provides the orthopedic surgeon with information regarding intra-articular findings, aiding treatment choices., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Purpose: Viable cartilage allograft (VCA) is a cartilage tissue matrix that contains cryopreserved viable allogeneic cartilage fibres. This study aimed to assess safety and benefits in treating focal knee cartilage defects with VCA. We hypothesized that VCA is a safe single-stage procedure in isolated chondral defects., Method: In vitro analysis, in vivo studies and a prospective case series were performed. VCA was evaluated in a goat cartilage repair model. Symptomatic International Cartilage Repair Society grade 3/4A lesions of the femoral condyle or patella were implanted with VCA. International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome (KOOS) subscales, Lysholm, Short Form-12, Visual Analog Scale and pain frequency levels were assessed. Radiographic and magnetic resonance imaging (MRI) was performed at regular intervals postoperatively. Data were analysed by statisticians to determine the power and significance of the results., Results: The goat study confirmed that VCA is effective for cartilage repair. Twenty patients were implanted; the mean age was 28.1 (16-56), the mean body mass index (BMI) was 27.9 ± 5.6 and the mean follow-up was 24.1 months (range = 12.0-36.0 months). Lesions were in either the femoral condyle (7) or patella (13). Lesion sizes ranged from 1.5 to 6.0 cm 2 (mean = 4.58 cm 2 ). Outcome scores improved from preoperative baseline (POB): IKDC (78.2), Lysholm (89.0), KOOS: Pain (95.8), Symptoms (86.3), ADL (87.8), Sports (85.0) and QOL (75.0). MRI imaging demonstrated excellent osteochondral allograft assimilation. Second-look arthroscopy (two patients) demonstrated complete fill and incorporation (Brittberg scores 11/12). Functional scores were maintained at 24 (M): IKDC (86.24 ± 17.2), Lysholm (87.23 ± 15.0), KOOS: Pain (91.72 ± 17.3), Symptoms (84.92 ± 16.1), ADLs (93.80 ± 16.1), Sports (84.45 ± 27.7), QOL (81.30 ± 20.8)., Conclusion: VCA is an off-the-shelf, single-stage, conformable allogeneic graft that treats chondral defects with no additional fixation. Preclinical and short-term prospective clinical studies show that VCA can safely treat chondral defects with potential advantages to existing options., Level of Evidence: Level IV study., (© 2024 The Authors. Knee Surgery, Sports Traumatology, Arthroscopy published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Purpose: To evaluate magnetic resonance image (MRI) findings in children and adolescents suffering from knee pain without traumatic or physical overload history and to identify potential anatomic risk factors., Material and Methods: A total of 507 MRIs of 6- to 20-year-old patients (251 males; 256 females) were evaluated with regard to detectable pathologies of the knee. The results were compared to a control group without pain ( n = 73; 34 males; 39 females). A binary logistic regression model and t-tests for paired and unpaired samples were used to identify possible risk factors and significant anatomic differences of the study population., Results: In 348 patients (68.6%), at least one pathology was detected. The most commonly detected finding was chondromalacia of the patellofemoral (PF) joint (n = 205; 40.4%). Chondral lesions of the PF joint occurred significantly more often in knee pain patients than in the control group (40% vs. 11.0%; p = 0.001), especially in cases of a patella tilt angle > 5° ( p ≤ 0.001), a bony sulcus angle > 150° ( p = 0.002), a cartilaginous sulcus angle > 150° ( p = 0.012), a lateral trochlear inclination < 11° ( p ≤ 0.001), a lateralised patella ( p = 0.023) and a Wiberg type II or III patella shape ( p = 0.019). Moreover, a larger patella tilt angle ( p = 0.021), a greater bony sulcus angle ( p = 0.042), a larger cartilaginous sulcus angle ( p = 0.038) and a lower value of the lateral trochlear inclination ( p = 0.014) were detected in knee pain patients compared to the reference group., Conclusion: Chondromalacia of the PF joint is frequently observed in children and adolescents suffering from non-overload atraumatic knee pain, whereby a patella tilt angle > 5°, a bony sulcus angle > 150°, a cartilaginous sulcus angle > 150°, a lateral trochlear inclination < 11°, a lateralised patella and a Wiberg type II or III patella shape seem to represent anatomic risk factors.

Background: Intra-articular (IA) platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) injections have shown efficacy and safety in treating osteoarthritis (OA). However, the effectiveness and mechanisms of combined intraosseous (IO) administration of these orthobiologics have yet to be explored., Purpose/hypothesis: The purpose of this study was to evaluate the effect on pain, cartilage, synovium/infrapatellar fat pad (IFP), and subchondral bone in rat knee OA, comparing isolated IA with combined IA and IO (IA+IO) injections of PRP or BMAC. It was hypothesized that combined injections would be superior to sole IA injections., Study Design: Controlled laboratory study., Methods: A total of 48 rats were divided into 6 groups: sham (only joint puncture during OA induction with IA+IO saline injection treatment) and 5 groups with OA induction, control (IA+IO saline injection), PRP (IA PRP+IO saline injection), BMAC IA (IA BMAC+IO saline injection), PRP IA+IO (IA+IO PRP injection), and BMAC IA+IO (IA+IO BMAC injection). OA was induced by IA injection of monosodium iodoacetate (MIA). Rats were administered different orthobiologics according to their grouping 3 weeks after the MIA injection. Pain changes were evaluated using the weightbearing ratio assay at weeks 3, 4, 5, 7, and 9 after OA induction. Rats were euthanized at week 9 for gross, radiological, histological, immunohistochemical, and immunofluorescence assessments of cartilage, synovium, and subchondral bone., Results: Compared with the control group, all orthobiologics injection groups had reduced joint pain. Compared with IA injection, IA+IO injections provided superior pain relief by suppressing calcitonin gene-related peptide and substance P in both the synovium/IFP and subchondral bone. IA+IO injections slowed the progression of subchondral bone lesions by inhibiting CD31 hi Emcn hi vessel formation and excessive osteoclast and osteoblast turnover while preserving subchondral bone microarchitecture, slowing cartilage degeneration. However, IA+IO injections did not outperform isolated IA injections in reducing synovitis and synovium/IFP fibrosis. Compared with PRP, BMAC exhibited superior inhibition of pain-related mediators, but no significant differences were observed in synovitis suppression, infrapatellar fat pad fibrosis, and subchondral bone protection., Conclusion: IA+IO injections of orthobiologics were more effective in relieving pain, slowing cartilage degeneration, and inhibiting abnormal vascularization and remodeling compared with isolated IA injections. BMAC showed superior pain relief in the synovium/IFP and subchondral bone compared with PRP. Further research is needed to optimize PRP and BMAC components for enhanced efficacy in OA management., Clinical Relevance: Our findings contribute to advancing the understanding of pain relief mechanisms and support the endorsement of IO injection of orthobiologics for the treatment of OA and joint pain., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This work was supported by the National Natural Science Foundation of China (82372490, 81972123, 82172508); Fundamental Research Funds for the Central Universities (2015SCU04A40); Innovative Spark Project of Sichuan University (2018SCUH0034); Chengdu Science and Technology Bureau Project (2019-YF05-00090-SN); 1·3·5 Project for Disciplines of Excellence of West China Hospital Sichuan University (ZYJC21030, ZY2017301); and 1·3·5 Project for Disciplines of Excellence–Clinical Research Incubation Project, West China Hospital, Sichuan University (2019HXFH039). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Purpose/aim: Cartilage injury and subsequent osteoarthritis (OA) are debilitating conditions affecting millions worldwide. As there are no cures for these ailments, novel therapies are needed to suppress disease pathogenesis. Given that joint injuries are known to produce damage-associated molecular patterns (DAMPs), our central premise is that the Toll-like receptor 4 (TLR4) pathway is a principal driver in the early response to cartilage damage and subsequent pathology. We postulate that TLR4 activation is initiated/perpetuated by DAMPs released following joint damage. Thus, antagonism of the TLR4 pathway immediately after injury may suppress the development of joint surface defects., Materials and Methods: Two groups were utilized: (1) 8-week-old, male C57BL6 mice treated systemically with a known TLR4 antagonist and (2) mice injected with vehicle control. A full-depth cartilage lesion on the midline of the patellofemoral groove was created in the right knee of each mouse. The left knee was used as a sham surgery control. Gait changes were evaluated over 4 weeks using a quantitative gait analysis system. At harvest, knee joints were processed for pathologic assessment, Nanostring® transcript expression, and immunohistochemistry (IHC)., Results: Short-term treatment with a TLR4 antagonist at 14-days significantly improved relevant gait parameters; improved cartilage metrics and modified Mankin scores were also seen. Additionally, mRNA expression and IHC showed reduced expression of inflammatory mediators in animals treated with the TLR4 antagonist., Conclusions: Collectively, this work demonstrates that systemic treatment with a TLR4 antagonist is protective to further cartilage damage 14-days post-injury in a murine model of induced disease.

Rationale and Objectives: The purpose of this study was to verify the feasibility of magnetic resonance fingerprinting (MRF)-derived synovial fluid fraction (SFF) mapping for quantifying subvoxel-sized cartilage defects., Materials and Methods: MRF was performed on a 3-Tesla scanner and used to derive T2 and SFF maps. An ex vivo experiment was performed using bovine bone; different numbers of holes (4, 6, 8, 10, and 12) were drilled separately on the articular surface, and SFF values were compared among the drilled areas. In a clinical study, 16 osteoarthritis patients underwent sagittal 3D fast spinecho (FSE) and MRF scanning, and knee cartilage segmentation was performed on each image. For morphologic analysis, fluid-excluded images of the SFF (FEI SFF ) and T2 maps (FEI T2 ) were generated using the cartilage segmentations, and the whole-organ magnetic resonance imaging score (WORMS) of each FEI and 3D FSE image were compared using the kappa coefficient. For quantitative analysis, intact cartilage volumes in the SFF (V SFF ) and T2 maps (V T2 ) were calculated, and their correlations with reference to the actual cartilage volume on 3D FSE images (V 3D ) were evaluated., Results: In the ex vivo experiment, the SFF value increased as the number of holes increased. The kappa coefficients of the WORMS were 0.80 and 0.64 in the SFF and T2 maps, respectively, and substantial to almost perfect agreement was observed in the medial tibiofemoral joint. The V 3D -V SFF and V 3D -V T2 correlation coefficients differed by 0.03 or more in the medial tibiofemoral joint., Conclusion: The MRF-derived SFF map can feasibly evaluate small, invisible cartilage defects and quantify cartilage volumes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objective: Pseudolesions of joints are known as focal irregularities of chondral or subchondral bone in typical joint areas and occur frequent but without clinical relevance. This study aims to report the prevalence and describe MRI findings of a previously unreported chondral, mostly posterior located pseudolesion of the distal tibia, and to define criteria to distinguish it from pathologic osteochondral lesions, as well as from another known pseudolesion of this area - the so called "Notch of Harty"., Material and Methods: A tri-centric retrospective case-control study included a total of 2,428 patients with ankle MRI examinations performed over a period of 6 years. MRI scans were evaluated by three radiologists in consensus for any cartilage irregularity of the distal tibial articular surface. For this purpose, the tibial articular surface was divided into 9 topographic regions. Proton-density weighted, fat-suppressed sequences in sagittal and coronal acquisition were used to assess the postero-medial articular surface of the tibia. Imaging features such as size and localization of cartilage irregularity and/or a cortical mould as well as presence of associated edema and/or subchondral cysts were reported. Demographic data (sex, age, and weight) was also recorded. Clinical data comprised presence of pain, movement impairment, and concomitant pathologies., Results: A total of 68 patients (34 male, 34 female) with a lesion of the distal tibia were identified that had a new pseudolesion (prevalence of 3%). These lesions occurred most frequently (50 out of 68, 74%) in the postero-medial distal tibia plafond and were more commonly detected in the age group of 9-30 years (47%). In 13 of these 68 cases, the cartilage irregularity was the sole lesion without subchondral abnormalities. By defining these cases as definite pseudolesions, the prevalence was 1% and their age distribution was similar to that of the 55 other lesions with subchondral changes. Here with 11 of the 13 cases the majority (85%) were seen in the posterior part, especially in the postero-medial part (55%) of the distal tibia. The size of the cartilage defect ranged from 1 to 7 mm, and the majority (69%) sized from 2 to 3 mm. In 36 of 68 patients, we have seen subchondral alterations such as edema and/or cysts in addition to cartilage irregularity. 66% (n = 45) of these changes were edema and 37% (n = 25) were cysts. None of these 68 new pseudolesions with or without subchondral changes needed surgical or arthroscopic intervention. In the radiological and orthopaedic reports, clinical symptoms such as pain or instability were never associated with our observed lesions and there was no significant correlation between the presence of motion-related pain and imaging findings of cartilage irregularity, subchondral edema, and subchondral cysts. Thirteen patients had MRI follow-up examinations. Here the lesions did not show any MR morphological changes or clinical deterioration. Besides the new pseudolesion, which occured mainly in the posterior part of the tibia surface, we observed the "Notch of Harty" with a higher prevalence (25%) in our patient cohort. The typical localization was in the antero-medial tibial articular surface, without any edema or cysts. There were no coincidences of patients with both a new pseudolesion and the "Notch of Harty" CONCLUSION: A new pseudolesion is typically seen in the postero-central and postero-medial tibial articular surface with a prevalence of 3% and may be associated with only a small cartilage irregularity. In many cases, however, additional findings such as bone edema and/or an adjacent bone cysts were found, which impairs differentiation of these lesions from pathologic osteochondral lesions. The latter are obviously often associated with a larger cartilage defect and clinical symptoms. Due to the balanced age distribution between those pseudolesions with and without subchondral changes and the lack of clinical symptoms, we conclude that the here reported pseudolesions are not a predilection for a clinically manifest osteochondral lesion (OCL). At the very least, the apparent lack of clinical relevance increases the likelihood that we are dealing with a new true pseudolesion., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Articular cartilage is a common cartilage type found in a multitude of joints throughout the human body. However, cartilage is limited in its regenerative capacity. A range of methods have been employed to aid adults under the age of 45 with cartilage defects, but other cartilage pathologies such as osteoarthritis are limited to non-steroidal anti-inflammatory drugs and total joint arthroplasty. Cell therapies and synthetic biology can be utilized to assist not only cartilage defects but have the potential as a therapeutic approach for osteoarthritis as well. In this review, we will cover current cell therapy approaches for cartilage defect regeneration with a focus on autologous chondrocyte implantation and matrix autologous chondrocyte implantation. We will then discuss the potential of stem cells for cartilage repair in osteoarthritis and the use of synthetic biology to genetically engineer cells to promote cartilage regeneration and potentially reverse osteoarthritis.

Objective: The aim of this study was to evaluate if a similar catabolic and inflammatory gene pattern exists between the synovium, hyaline cartilage, and blood of patients with the knee joint tissues and if one precedes the other., Design: A total of fifty-eight patients (34 females and 24 males) with a mean age of 44.7 years (range, 18-75) underwent elective knee arthroscopy due to previously diagnosed pathology. Full blood samples were collected preoperatively from synovium and cartilage samples intraoperatively. Real time PCR with spectrophotometric analysis was performed. Following genes taking part in ECM (extracellular matrix) remodeling were selected for analysis: MMP-1, MMP-2, MMP-8, MMP-9, MMP-13, MMP-14, ADAMTS-4 (Agg1) and ADAMTS-5 (Agg2) proteases, TIMP-1, and TIMP-2 - their inhibitors - and IL-1 and TNF-α cytokines., Results: Analysis revealed a strong and significant correlation between gene expression in synovial and systemic blood cells (p <0.05 for all studied genes) with ADAMTS-4, ADAMTS-5, IL-1, TNF-α and TIMP-2 expression most positively correlated with an R>0.8 for each. An analysis between chondrocytes and systemic blood gene expression shown no significant correlation for all genes. Bivariate correlation of International Cartilage Repair Society grading and genes expression revealed significant associations with synovial MMP-1, MMP-2, MMP-8, MMP-9, IL-1, TNF-α and TIMP-2., Conclusion: We suggest that the synovial tissue is the first responder for knee joint stress factors in correlation with the response of blood cells. The chondrocyte's genetic response must be further investigated to elucidate the genetic program of synovial joints, as an organ, during OA development and progression., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Articular cartilage lesions remain a major challenge for clinicians and researchers. Several techniques, such as histological scoring, magnetic resonance imaging, and tissue section staining, are available for detecting cartilage degeneration and lesions and evaluating cartilage repairs. Nevertheless, these methods are complex and have numerous influencing factors, which may present obstacles to efficient communication between studies. In this study, we developed a fluorescence observation system that integrated a two-photon laser scanning confocal microscope (TPLSCM) with the second-harmonic generation (SHG) of a cartilage matrix. The observation system enabled the detection of autofluorescence emitted by the cartilage matrix without species specificity, facilitating both qualitative and quantitative analyses of the cartilage matrix. Notably, this observation could be applied three-dimensionally to a fresh specimen in situ up to a depth of 300 μm, obviating the need for traditional histological fixation, slicing, or staining. Furthermore, using this observation system, we reconstructed a three-dimensional (3D) image and a 3D model of the cartilage matrix. The utilization of the 3D fluorescence model may serve as a dependable option for the fabrication of cartilage matrix biomimetic scaffolds in future studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This study investigates whether infrapatellar fat pad (IPFP) elasticity is associated with anterior knee pain in patients with knee osteoarthritis (KOA). The IPFP elasticity of 97 patients with KOA (Kellgren and Lawrence [KL] grades of the femorotibial and patellofemoral joints ≥ 2 and ≤ 2, respectively), aged 46-86 years, was evaluated via shear wave speed using ultrasound elastography. The patients were divided into two groups according to the presence or absence of anterior knee pain. Univariate analyses were used to compare patient age, sex, femorotibial KL grade, magnetic resonance imaging findings (Hoffa, effusion synovitis, bone marrow lesion scores, and IPFP size), and IPFP elasticity between the groups. Multivariate logistic regression analyses were subsequently performed using selected explanatory variables. IPFP elasticity was found to be associated with anterior knee pain in the univariate (p = 0.007) and multivariate (odds ratio: 61.12, 95% CI 1.95-1920.66; p = 0.019) analyses. Anterior knee pain is strongly associated with stiffer IPFPs regardless of the femorotibial KL grade, suggesting that ultrasound elastography is useful for the diagnosis of painful IPFP in patients with KOA., (© 2023. The Author(s).)

Cartilage MRI-based T 1rho and T 2 compositional measurements have been developed to characterize cartilage matrix quality and diagnose cartilage damage before irreversible defects are found, allowing intervention at an early, potentially reversible disease stage. Over the last 2 decades, this technology was investigated in numerous studies and was validated using specimen studies and arthroscopy; and longitudinal studies documented its ability to predict progression of degenerative disease and radiographic osteoarthritis (OA). While T 1rho and T 2 measurements have shown promise in early disease stages, several hurdles have been encountered to apply this technology clinically. These include (i) challenges with cartilage segmentation, (ii) long image acquisition times, (iii) a lack of standardization of imaging, and (iv) an absence of reference databases and definitions of abnormal cut-off values. Progress has been made by developing deep-learning based automatic cartilage segmentation and faster imaging methods, enabling the feasibility of T 1rho and T 2 imaging for clinical and scientific trial applications. Also, the Radiological Society of North America (RSNA) Quantitative Imaging Biomarker Alliance mechanism was used to establish standardized profiles for compositional T 1rho and T 2 imaging, and multi-center feasibility testing is work in progress. The last hurdles are the development of reference databases and establishing a definition of normal versus abnormal cartilage T 1rho and T 2 values. Finally, effective treatments for prevention and slowing progression of OA are required in order to establish T 1rho and T 2 as imaging biomarkers for initiating and monitoring therapies, analogous to the role of dual X-ray absorptiometry (DXA) bone mineral density measurements in the management of osteoporosis. KEY POINTS: • T 1rho and T 2 cartilage measurements have been validated in characterizing cartilage degenerative change using histology and arthroscopy as a reference. • They have also been shown to predict progression of cartilage degeneration and incidence of radiographic OA. • Advances have been made to facilitate clinical and trial application of T 1rho and T 2 by improved standardization of imaging and by establishing deep learning-based automatic cartilage segmentation. • Effective treatments with disease-modifying OA specific drugs may establish T 1rho and T 2 cartilage compositional measurements as biomarkers to initiate and monitor treatment., (© 2023. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Background: It has not been clarified yet how much force is acting on the shoulder joint to create Hill-Sachs/reverse Hill-Sachs lesions which are commonly observed in patients with anterior or posterior shoulder instability. The purpose of this study was to determine the magnitude of force to create these bony lesions using cadaveric shoulders., Methods: Fourteen fresh-frozen cadaveric shoulders were used. Compression tests were performed using the universal testing machine. The specimens were randomly divided into two groups. In group A, the posterior humeral head (the bare area and articular cartilage) was first compressed against the anterior glenoid rim to simulate a Hill-Sachs lesion, followed by the anterior humeral head being compressed against the posterior glenoid rim. In group B, the same procedure was repeated in the reverse order. X-ray microcomputed tomography (microCT) was also performed., Results: The maximum compression force to create a Hill-Sachs lesion was 771 ± 214 N (mean ± SD) on the articular cartilage of the posterior humeral head, which was significantly greater than the force of 447 ± 215 N to create it on the bare area (P = 0.0086). Regarding the reverse Hill-Sachs lesions, the maximum compression force was 840 ± 198 N when it was created on the articular cartilage of the anterior humeral head, which was significantly greater than the force of 471 ± 100 N when it was created at the footprint of the subscapularis tendon (P = 0.0238). MicroCT showed multiple breakage of the trabecular bone., Conclusion: A force to create a Hill-Sachs lesion or a reverse Hill-Sachs lesion was significantly greater when it was created on the humeral articular cartilage than at the non-cartilage area. Also, the force to create a reverse Hill-Sachs lesion was significantly greater than the one to create a Hill-Sachs lesion., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

A joint contains many different tissues that can exhibit pathological changes, providing many potential targets for treatment. Researchers are increasingly suggesting that osteoarthritis (OA) comprises several phenotypes or subpopulations. Consequently, a treatment for OA that targets only one pathophysiologic abnormality is unlikely to be similarly efficacious in preventing or delaying the progression of all the different phenotypes of structural OA. Five structural phenotypes have been proposed, namely the inflammatory, meniscus-cartilage, subchondral bone, and atrophic and hypertrophic phenotypes. The inflammatory phenotype is characterized by marked synovitis and/or joint effusion, while the meniscus-cartilage phenotype exhibits severe meniscal and cartilage damage. Large bone marrow lesions characterize the subchondral bone phenotype. The hypertrophic and atrophic OA phenotype are defined based on the presence large osteophytes or absence of any osteophytes, respectively, in the presence of concomitant cartilage damage. Limitations of the concept of structural phenotyping are that they are not mutually exclusive and that more than one phenotype may be present. It must be acknowledged that a wide range of views exist on how best to operationalize the concept of structural OA phenotypes and that the concept of structural phenotypic characterization is still in its infancy. Structural phenotypic stratification, however, may result in more targeted trial populations with successful outcomes and practitioners need to be aware of the heterogeneity of the disease to personalize their treatment recommendations for an individual patient. Radiologists should be able to define a joint at risk for progression based on the predominant phenotype present at different disease stages., (© 2022. The Author(s).)

Imaging plays a pivotal role in osteoarthritis research, particularly in epidemiological and clinical trials of knee osteoarthritis (KOA), with the ultimate goal being the development of an effective drug treatment for future prevention or cessation of disease. Imaging assessment methods can be semi-quantitative, quantitative, or a combination, with quantitative methods usually relying on software to assist. The software generally attempts image segmentation (outlining of relevant structures). New techniques using artificial intelligence (AI) or deep learning (DL) are currently a frequent topic of research. This review article provides an overview of the literature to date, focusing primarily on the current status of quantitative software-based assessment techniques of KOA using magnetic resonance (MR) imaging. We will concentrate on the imaging evaluation of three specific structural imaging biomarkers: bone marrow lesions (BMLs), meniscus, and synovitis consisting of effusion synovitis (ES) and Hoffa's synovitis (HS). A brief clinical and imaging background review of osteoarthritis evaluation, particularly relating to these three structural markers, is provided as well as a general summary of the software methods. A summary of the literature with respect to each KOA assessment method will be presented overall as well as with respect to each specific biomarker individually. Novel techniques, as well as future goals and directions using quantitative imaging assessment, will be discussed., (© 2023. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

The existing methods for analyzing patellofemoral (PF) osteoarthritis (OA) are limited. Our purpose was to clarify the frequency, localization, and morphological progression of PFOA by observing three-dimensional (3D) magnetic resonance (MR) images from a cohort population. The subjects were 561 patients aged 30-79 years from the Kanagawa Knee Study who had not visited a hospital for more than three consecutive months for knee symptoms. MR images of the PF joints, separated into the medial and lateral types, were presented in order of the highest to lowest patella cartilage area ratios. Cartilage defects in the patella were detected in 37 subjects (6.6%). Medial lesions (4.6%) were significantly more frequent than lateral lesions (2.0%) (p < 0.01). For both medial and lateral lesions, the patellar cartilage defects were divided into confined and unconfined types. The 3D MR images of the PF joint showed that the patellar cartilage defect occurred along each ridge of the femoral trochlea. The 3D MR images revealed a 6.6% prevalence of patellar cartilage defects, higher in the medial than lateral regions. The 3D MR images can easily determine PF morphology and cartilage defect location, making them useful in understanding the pathophysiology and etiology of PFOA., (© 2023. Springer Nature Limited.)

Objective: Bone Marrow Lesions (BMLs) are areas in bone with high fluid signal on MRI associated with painful and progressive OA. While cartilage near BMLs in the knee has been shown to be degenerated, this relationship has not been investigated in the hip., Research Question: is T1Gd lower in areas of cartilage overlying BMLs in the hip?, Design: 128 participants were recruited from a population-based study of hip pain in 20-49-year-olds. Proton-density weighted fat-suppressed and delayed Gadolinium Enhanced MR Imaging of Cartilage (dGEMRIC) images were acquired to locate BMLs and quantify hip cartilage health. BML and cartilage images were registered and cartilage was separated into BML overlying and surrounding regions. Mean T1Gd was measured in 32 participants with BMLs in both cartilage regions and in matched regions in 32 age- and sex-matched controls. Mean T1Gd in the overlying cartilage was compared using linear mixed-effects models between BML and control groups for acetabular and femoral BMLs, and between cystic and non-cystic BML groups., Results: Mean T1Gd of overlying cartilage was lower in the BML group compared to the control group (acetabular: -105 ms; 95% CI: -175, -35; femoral: -8 ms; 95% CI: -141, 124). Mean T1Gd in overlying cartilage was lower in cystic compared to non-cystic BML subjects, but the confidence interval is too large to provide certainty in this difference (-3 [95% CI: -126, 121])., Conclusions: T1Gd is reduced in overlying cartilage in hips from a population-based sample of adults aged 20-49, which suggests BMLs are associated with local cartilage degeneration in hips., Competing Interests: Declaration of Competing Interest BBF has an equity position in a private imaging clinic which includes MRI in Vancouver BC. The clinic was not involved in this work. The other authors have no conflicts of interest to disclose., (Copyright © 2023 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Purpose: The aim of this study was to evaluate the relationship between the grade of signal change of the pericruciate fat pad (PCFP) and the location and severity of cartilage alterations in the knee on magnetic resonance imaging (MRI)., Materials and Methods: This retrospective study included 234 patients (M:F = 96:138, mean: 51 years) who underwent knee MRI. Two experienced musculoskeletal radiologists assessed any PCFP alterations (as grades 0-3) and chondral lesions using the modified Outerbridge grade (as grades 0-4). Bone marrow lesions (BMLs), meniscal status, anterior cruciate ligament alterations, and effusion-synovitis were also evaluated on the MRI. The relationships between PCFP alteration and MR findings (including the grade of chondral lesion) were evaluated., Results: Signal changes in the PCFP were detected in 150 cases by Reader 1 (grade 0, 67 cases; grade 1, 53 cases; grade 2, 21 cases; grade 3, 9 cases) and in 154 cases by Reader 2 (grade 0, 59 cases; grade 1, 61 cases; grade 2, 24 cases; grade 3, 10 cases). The grade of PCFP signal change was statistically significantly correlated with the grade of the chondral lesion of the medial femoral condyle (MFC) (p = 0.029 and p = 0.003, respectively) and the medial tibial plateau (MTP) (p = 0.045, p = 0.002, Readers 1 and 2, respectively). The grade of PCFP signal change was significantly correlated with the grade of the BMLs of the MFC, MTP, and lateral femoral condyle (p < 0.05) for both readers. PCFP alteration was related to effusion-synovitis and tears of the medial meniscus., Conclusions: The grade of PCFP signal change was correlated with the severity of the cartilage alteration in the medial compartment of the knee joint and was also correlated with BMLs in the medial compartment, medial meniscal tears, and synovitis. Therefore, signal change in the PFCP seen on MRI can be an additional clue of the presence of osteoarthritis in the knee, particularly in the medial compartment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Current cartilage repair therapies do not re-create the complex mechanical interface between cartilage and bone, which is critical for long-term repair durability. New biomaterial designs that include hard tissue-soft tissue interface structures offer promise to improve clinical outcomes., Purpose/hypothesis: The purpose of this study was to evaluate the efficacy and safety of a naturally derived osteochondral biotemplate with a novel contiguous hard tissue-soft tissue interface in an ovine model as a regenerative solution for articular cartilage defects. It was hypothesized that the osteochondral biotemplate would produce structurally superior repair tissue compared with microfracture over a 13-month period., Study Design: Controlled laboratory study., Methods: Osteochondral biotemplates were manufactured from porcine cancellous bone. Skeletally mature sheep (N = 30) were randomly allocated to 3 groups: early healing stage (euthanasia at 4 months), 6-month treatment, and 13-month treatment. In the early healing stage group, an 8 mm-diameter by 5 mm-deep osteochondral defect was created on the medial femoral condyle and treated at the time of iatrogenic injury with an osteochondral biotemplate. The contralateral limb received the same treatment 2 months later. In the 6- and 13-month treatment groups, 1 limb received the same osteochondral procedure as the early healing stage group. In the contralateral limb, an 8 mm-diameter, full-thickness cartilage defect (1-2 mm deep) was created and treated with microfracture. Cartilage repair and integration were quantitatively and qualitatively assessed with gross inspection, histological evaluation, and magnetic resonance imaging (MRI). Wilcoxon signed-rank and McNemar tests were used to compare the treatments., Results: At 6 and 13 months after treatment, the biotemplate was not present histologically. At 13 months, the biotemplate treatment demonstrated statistically higher histological scores than microfracture for integration with surrounding cartilage (biotemplate: 74 ± 31; microfracture: 28 ± 39; P = .03), type 2 collagen (biotemplate: 72 ± 33; microfracture: 40 ± 38; P = .02), total cartilage (biotemplate: 71 ± 9; microfracture: 59 ± 9; P = .01), and total integration (biotemplate: 85 ± 15; microfracture: 66 ± 20; P = .04). The osteochondral biotemplate treatment produced a notable transient nonneutrophilic inflammatory response that appeared to approach resolution at 13 months. MRI results were not statistically different between the 2 treatments., Conclusion: Even with the inflammatory response, after 13 months, the osteochondral biotemplate outperformed microfracture in cartilage regeneration and demonstrated superiority in integration between the repair tissue and host tissue as well as integration between the newly formed cartilage and the underlying bone., Clinical Relevance: This work has demonstrated the clinical potential of a novel biomaterial template to regenerate the complex mechanical interface between cartilage and the subchondral bone., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: D.A.D. and E.A.N. are owners of Advanced Regenerative Tech, a small company with a license to the patent that comprises the biomaterial described herein. D.A.D. and E.A.N. are inventors on the patent that has been issued for the material described in this work, US Patent 8702809. L.A.F. has received consulting fees and research support from Arthrex. H.G.P. has received consulting fees from Stryker Corporation and Smith & Nephew, speaking compensation from Arthrex, research support from GE HealthCare, and travel expenses from Siemens Medical Solutions. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Background: Retrograde drilling remains technically challenging, because of the difficulty of identifying the accurate location of cysts during surgery. This study's aim was to evaluate the 3-dimensional (3D) image-based surgical navigation-assisted endoscopic retrograde drilling technique for subchondral bone lesions of the talus., Methods: From March 2017 to June 2020, a total of 21 cases with Hepple stage V subchondral bone lesions of the talus were treated with 3D image-based surgical navigation-assisted endoscopic retrograde drilling and bone graft technique. Arthroscopic views were categorized per Pritsch classifications. The correlation between the drilled tunnel with preoperative cystic lesions were assessed under postoperative computer tomographic (CT) scans. The American Orthopaedic Foot & Ankle Society (AOFAS) scores, visual analog scale (VAS) scores, and Foot and Ankle Ability Measure (FAAM) sports scales were evaluated at the preoperative and final consultation. All complications were recorded., Results: On postoperative CT scans, in 20 cases (95.2%), the drilled tunnel was judged to have been in the center of previous cysts. Only 9 cases (42.9%) showed intact normal cartilage (grade 0, group A); 12 cases (57.1%) had intact, but soft, cartilage (grade I, group B). The median follow-up time was 24 (24, 30) months, and at final follow-up, there were no significant differences between the mean AOFAS and VAS scores in both groups (89.0 ± 6.4 vs 88.3 ± 7.0 and 1 vs 0.5) or postoperative FAAM sports scales (28.2 ± 2.2 vs 26.6 ± 4.9, P  = .363). Two patients had revision surgery in group B., Conclusion: The 3D image-based surgical navigation-assisted endoscopic retrograde drilling and bone graft technique for the subchondral bone lesions of the talus in this small case series showed encouraging results., Level of Evidence: Level IV, retrospective case series., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. ICMJE forms for all authors are available online.

It was aimed to investigate the relationship between magnetic resonance imaging (MRI) measurements of trochlear and patellar morphology and grade 3-4 patellar chondromalacia. Grade 3-4 patellar chondromalacia group, and an age- and sex-matched control group with normal patellar joint cartilage were comprised. For trochlear morphology evaluation in MRI; sulcus angle, trochlear angle, lateral trochlear inclination angle and medial trochlear inclination angle were measured. For patellar morphology evaluation; patella trochlear ratio, insall-salvati ratio, modified Insall- Salvati ratio and Blackburne-Peel ratio were measured. Obtained measurements were statistically analyzed according to demographic characteristics. One hundred and twenty-five patients with chondromalacia and 125 controls participated. The sulcus angle and the trochlear angle were significantly higher in the patellar chondromalacia group (p<0.05). The lateral trochlear inclination angle was significantly less in the patellar chondromalacia group (p=0.011). There was no significant difference between the groups in terms of medial trochlear inclination angle (p=0.520). There was no significant difference between the groups in terms of patella-trochlear ratio (p=0.617). Insall-Salvati ratio was significantly higher in the patellar chondromalacia group (p=0.003). Modified Insall-Salvati ratio was significantly lower in the patellar chondromalacia group (p=0.001). The rate of Blackburne-Peel was significantly higher in the patellar chondromalacia group (p=0.004). Measurements of sulcus angle, trochlear angle, lateral trochlear inclination angle, Insall-Salvati ratio, modified Insall-Salvati ratio, Blackburne-Peel ratio have diagnostic value for grade 3-4 chondromalacia.

Objective: Assessment of human joint cartilage is a crucial tool to detect and diagnose pathological conditions. This exploratory study developed a workflow for 3D modeling of cartilage and bone based on multimodal imaging. New evaluation metrics were created and, a unique set of data was gathered from healthy controls and patients with clinically evaluated degeneration or trauma., Design: We present a novel methodology to evaluate knee bone and cartilage based on features extracted from magnetic resonance imaging (MRI) and computed tomography (CT) data. We developed patient specific 3D models of the tibial, femoral, and patellar bones and cartilages. Forty-seven subjects with a history of degenerative disease, traumatic events, or no symptoms or trauma (control group) were recruited in this study. Ninety-six different measurements were extracted from each knee, 78 2D and 18 3D measurements. We compare the sensitivity of different metrics to classify the cartilage condition and evaluate degeneration., Results: Selected features extracted show significant difference between the 3 groups. We created a cumulative index of bone properties that demonstrated the importance of bone condition to assess cartilage quality, obtaining the greatest sensitivity on femur within medial and femoropatellar compartments. We were able to classify degeneration with a maximum recall value of 95.9 where feature importance analysis showed a significant contribution of the 3D parameters., Conclusion: The present work demonstrates the potential for improving sensitivity in cartilage assessment. Indeed, current trends in cartilage research point toward improving treatments and therefore our contribution is a first step toward sensitive and personalized evaluation of cartilage condition.

Objective: The medial femoral condyle of the knee exhibits some of the highest incidences of chondral degeneration. However, a dearth of healthy human tissues has rendered it difficult to ascertain whether cartilage in this compartment possesses properties that predispose it to injuries. Assessment of young, healthy tissue would be most representative of the tissue's intrinsic properties., Design: This work examined the topographical differences in tribological, tensile, and compressive properties of young (n = 5, 26.2 ± 5.6 years old), healthy, human medial femoral condyles, obtained from viable allograft specimens. Corresponding to clinical incidences of pathology, it was hypothesized that the lowest mechanical properties would be found in the posterior region of the medial condyle, and that tissue composition would correspond to the established structure-function relationships of cartilage., Results: Young's modulus, ultimate tensile strength, aggregate modulus, and shear modulus in the posterior region were 1.0-, 2.8-, 1.1-, and 1.0-fold less than the values in the anterior region, respectively. Surprisingly, although glycosaminoglycan content is thought to correlate with compressive properties, in this study, the aggregate and shear moduli correlated more robustly to the amount of pyridinoline crosslinks per collagen. Also, the coefficient of friction was anisotropic and ranged 0.22-0.26 throughout the condyle., Conclusion: This work showed that the posteromedial condyle displays lower tensile and compressive properties, which correlate to collagen crosslinks and may play a role in this region's predisposition to injuries. Furthermore, new structure-function relationships may need to be developed to account for the role of collagen crosslinks in compressive properties.

Background: Osteoarthritis (OA) is the most prevalent chronic degenerative joint disease among the aged population. However, current treatments for OA are limited to alleviating symptoms, with no therapies that prevent and regenerate cartilage deterioration., Purpose: To assess the effects of platelet-derived exosomes (Plt-exos) on OA and then to explore the potential molecular mechanism., Study Design: Controlled laboratory study., Methods: Exosomes derived from human apheresis platelets were isolated and identified. The effects of Plt-exos in protecting chondrocytes under interleukin 1β stimulation were evaluated by analyzing the proliferation and migration in human primary chondrocytes. RNA sequencing was later performed in vitro for primary chondrocytes to reveal the underlying mechanisms of Plt-exo treatment. Anterior cruciate ligament transection was used to construct an OA mice model, and intra-articular injection of Plt-exos was given once a week for 6 weeks. Mice were sacrificed 4 weeks after the last injection. Histologic and immunohistochemistry staining and micro-computed tomography analysis were performed to assess alterations of articular cartilage and subchondral bone., Results: Plt-exos significantly promoted proliferation and migration of chondrocytes within a dose-dependent manner, as well as dramatically promoted cartilage regeneration and attenuated abnormal tibial subchondral bone remodeling, thus slowing the progression of OA. After being treated with Plt-exos, 1797 genes were differentially expressed in chondrocytes (923 upregulated and 874 downregulated genes). Functional enrichment results and hub genes were mainly involved in anti-inflammatory effects, mediating cell adhesion, stimulating cartilage repair, promoting anabolism, and inhibiting catabolism., Conclusion: Our results demonstrated that Plt-exos promoted chondrocyte proliferation and migration in vitro, as well as attenuated cartilage degeneration, improved the microarchitecture of subchondral bone, and retarded OA progression in vivo., Clinical Relevance: Our study illustrated that the administered Plt-exos could alleviate knee OA by attenuating cartilage degeneration and subchondral bone loss, possibly serving as a novel promising treatment for OA in the future.

Purpose: To compare the evaluation metrics for deep learning methods that were developed using imbalanced imaging data in osteoarthritis studies., Materials and Methods: This retrospective study utilized 2996 sagittal intermediate-weighted fat-suppressed knee MRIs with MRI Osteoarthritis Knee Score readings from 2467 participants in the Osteoarthritis Initiative study. We obtained probabilities of the presence of bone marrow lesions (BMLs) from MRIs in the testing dataset at the sub-region (15 sub-regions), compartment, and whole-knee levels based on the trained deep learning models. We compared different evaluation metrics (e.g., receiver operating characteristic (ROC) and precision-recall (PR) curves) in the testing dataset with various class ratios (presence of BMLs vs. absence of BMLs) at these three data levels to assess the model's performance., Results: In a subregion with an extremely high imbalance ratio, the model achieved a ROC-AUC of 0.84, a PR-AUC of 0.10, a sensitivity of 0, and a specificity of 1., Conclusion: The commonly used ROC curve is not sufficiently informative, especially in the case of imbalanced data. We provide the following practical suggestions based on our data analysis: 1) ROC-AUC is recommended for balanced data, 2) PR-AUC should be used for moderately imbalanced data (i.e., when the proportion of the minor class is above 5% and less than 50%), and 3) for severely imbalanced data (i.e., when the proportion of the minor class is below 5%), it is not practical to apply a deep learning model, even with the application of techniques addressing imbalanced data issues., Competing Interests: Declaration of Competing Interest S. L.: No relevant relationships. F. R.: Shareholders of BICL, LLC. Consultant to Calibr-California Institute of Biomedical Research and Grunenthal. Y. G.: No relevant relationships. E. J. B.: No relevant relationships. Z.-M. L.: No relevant relationships. A. G.: Consultant to Pfizer, Novartis, Regeneron, TissueGene, Merck Serono, and AstraZeneca. Shareholders of BICL, LLC. L. S.: No relevant relationships. C. E.: No relevant relationships. M.C.H.: Perform consulting activities, including attendance at virtual Advisory Board meetings, for the following entities: Acadia Pharmaceuticals, Bioclinica, Biosplice Therapeutics, BriOri Biotech, Centrexion Therapeutics, Eli Lilly, Dompe, Flexion Therapeutics Inc., Genascience, Gilead, GlaxoSmithKline, Kolon TissueGene, Novartis Pharma AG, Pfizer Inc., Regenosine, SFJ Pharmaceuticals Inc., Theralogix LLC, TrialSpark, WCG Analgesics Solutions, and Xalud Therapeutics. Member of Data Safety Monitoring Committees for clinical trials coordinated by ACI Clinical, Covance Inc., Cytel, ICON plc, IQVIA, and MiMedRx. Receive royalties from Elsevier (Editor, Rheumatology 7e and Editor-in-Chief, Seminars in Arthritis and Rheumatism) and Wolters Kluwer (UpToDate™). Stock options in BriOri Biotech, Regenosine, and Theralogix LLC. D. J. H.: Provides consulting advice on scientific advisory boards for Pfizer, Lilly, TLCBio, Novartis, Tissuegene, and Biobone. M.C.N.: No relevant relationships. W. W.: Employee and shareholder of Chondrometrics GmbH. C. K. K.: Consultant to Regeneron, LG Chem, Novartis, Xalud Therapeutics, and Express Scripts. He is the principal investigator for pharma-sponsored clinical trials to Abbvie, Cumberland, and GSK and DSMB to Kolon TissueGene and Avalor Therapeutics. X. S.: No relevant relationships., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Fibroblast growth factor 7 (FGF7), also known as keratinocyte growth factor (KGF), shows a crucial biological significance in tissue development, wound repair, tumorigenesis, and immune reconstruction. In the skeletal system, FGF7 directs the cellular synaptic extension of individual cells and facilities functional gap junction intercellular communication of a collective of cells. Moreover, it promotes the osteogenic differentiation of stem cells via a cytoplasmic signaling network. For cartilage, reports have indicated the potential role of FGF7 on the regulation of key molecules Cx43 in cartilage and Runx2 in hypertrophic cartilage. However, the molecular mechanism of FGF7 in chondrocyte behaviors and cartilage pathological process remains largely unknown. In this review, we systematically summarize the recent biological function of FGF7 and its regulatory role on chondrocytes and cartilage diseases, especially through the hot focus of two key molecules, Runx2 and Cx43. The current knowledge of FGF7 on the physiological and pathological processes of chondrocytes and cartilage provides us new cues for wound repair of cartilage defect and therapy of cartilage diseases., Competing Interests: Declaration of competing interest The authors declare that no competing interests exist., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Medial meniscus extrusion (MME) refers to the protrusion of the medial meniscus beyond the tibial edge by more than 3 mm, leading to a deficiency of the hoop strain. MME commonly occurs in conjunction with osteoarthritis (OA) or medial meniscal tears (MMT). However, factors associated with concomitant MME in patients with OA or MMT have not been systematically reviewed. This study aims to perform a systematic review and meta-analysis to identify factors associated with concomitant MME in OA or MMT., Methods: The systematic review of the literature was performed according to PRISMA. A literature search was conducted in 4 databases. All original human studies that reported the available evidence on factors associated with concomitant MME in patients with OA or MMT were included. Pooled binary variables were analyzed by odds ratios (OR) and 95% CIs, and pooled continuous variables were evaluated by mean difference (MD) and 95% CIs., Results: Ten studies on OA (5993 patients) and eight studies on MMT (872 patients) met the inclusion criteria. The overall pooled incidence of MME was 43% (95% CI, 37-50%) for OA, 61% (95% CI 43-77%) for MMT, and 85% (95% CI 72-94%) for medial meniscal root tears (MMRT). For the population with OA, Factors significantly associated with MME included radiographic OA [OR 4.24; 95% CI 3.07-5.84; P < 0.0001], bone marrow lesions [OR, 3.35; 95% CI 1.61-6.99; P = 0.0013], cartilage damage [OR, 3.25; 95% CI 1.60-6.61; P = 0.0011], and higher body mass index (BMI) [MD, 1.81; 95% CI 1.15-2.48; P < 0.0001]. Factors strongly associated with increased risk of MME for MMT included medial meniscal root [OR, 8.39; 95% CI 2.84-24.82; P < 0.0001] and radial tears [OR, 2.64; 95% CI 1.18-5.92; P < 0.0001]., Conclusion: Radiographic OA, bone marrow lesions, cartilage damage, and higher BMI were significantly associated with concomitant MME with OA. Furthermore, medial meniscal root and radial tears were significantly associated with an increased risk of MME in patients with MMT., Level of Evidence: IV., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Background: Focal cartilage lesions represent a common source of knee pain and disability, with the potential for the development and progression of osteoarthritis. Currently, microfracture (MFx) represents the most utilized first-line surgical treatment for small, focal chondral lesions. Recent investigations have examined methods of overcoming the limitations of MFx utilizing various augmentation techniques., Purpose: To perform a systematic review and meta-analysis evaluating clinical and radiographic outcomes in patients undergoing isolated MFx versus MFx augmented with orthobiologics or scaffolds for focal chondral defects of the knee., Study Design: Systematic review and meta-analysis; Level of evidence, 4., Methods: A systematic review was performed to identify studies evaluating outcomes and adverse events in patients undergoing isolated MFx versus augmented MFx for focal chondral defects in the knee from 1945 to June 1, 2021. Data were extracted from each article that met the inclusion/exclusion criteria. Meta-analyses were performed for all outcomes reported in a minimum of 3 studies., Results: A total of 14 studies were identified, utilizing 7 different types of injectable augmentation regimens and 5 different scaffolding regimens. Across the 14 studies, a total of 744 patients were included. The mean patient age was 46.8 years (range, 34-58 years), and 58.3% (n = 434/744) of patients were women. The mean final follow-up time was 26.7 months (range, 12-60 months). The mean chondral defect size ranged from 1.3 to 4.8 cm 2 . A post hoc analysis comparing mean improvement in postoperative outcomes scores compared with preoperative values found no significant differences in the improvement in the visual analog scale (VAS), International Knee Documentation Committee (IKDC), or Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores between patients undergoing isolated MFx and those undergoing MFx + augmentation. Patients undergoing MFx + augmentation reported significantly greater improvements in the Lysholm score and postoperative MOCART (magnetic resonance observation of cartilage repair tissue) scores compared with the isolated MFx group., Conclusion: Patients undergoing combined MFx + augmentation reported significant improvements in mean Lysholm and MOCART scores, without significant improvements in VAS, IKDC, or WOMAC scores when compared with patients undergoing isolated MFx.

Background: Microfracture (MF) is frequently performed as a first-line treatment for articular cartilage defects. Although good clinical outcomes are often obtained in the short term, poor clinical outcomes sometimes occur because of subchondral bone deterioration. The condition of the subchondral bone treated with MF may affect the repair of the osteochondral unit., Purpose: To analyze histological findings of the osteochondral unit after performing MF on subchondral bone in different states-normal, absorption, and sclerosis-in a rat model., Study Design: Controlled laboratory study., Methods: Full-thickness cartilage defects (5.0 × 3.0 mm) were created in the weightbearing area of the medial femoral condyle in both knees of 47 Sprague-Dawley rats. Five MF holes were created within the cartilage defect using a 0.55-mm needle to a depth of 1 mm at 0 weeks (normal group), 2 weeks (absorption group), and 4 weeks (sclerosis group) after the cartilage defect was created. In the left knee, MF holes were filled with β-tricalcium phosphate (β-TCP). At 2 and 4 weeks after MF, knee joints were harvested and histologically analyzed., Results: MF holes were enlarged at 2 weeks and further enlarged at 4 weeks in all groups. In the absorption group, osteoclast accumulation around the MF holes and cyst formation were observed. The trabecular bone surrounding the MF holes was thickened in the sclerosis group. The diameter of the MF hole was largest in the absorption group at 2 and 4 weeks after MF compared with the other groups. No subchondral bone cysts were observed after β-TCP implantation. Pineda scores in all groups were significantly better with β-TCP implantation than without β-TCP implantation at 2 and 4 weeks., Conclusion: MF for subchondral bone with bone absorption induced enlargement of the MF holes, cyst formation, and delay of cartilage defect coverage. Implantation of β-TCP into the MF holes enhanced remodeling of the MF holes and improved repair of the osteochondral unit compared with MF only. Therefore, the condition of the subchondral bone treated with MF affects repair of the osteochondral unit in a cartilage defect.

Purpose: Articular cartilage is vulnerable to multiple types of damage and it has limited reparative and regenerative capacities due to its absence of vascularity. Although a large number of therapeutic strategies exist to treat chondral defects, they have some limitations, such as fibrocartilage formation. Therefore, the goal of the present study was to evaluate the chondrogenic regenerative properties of an autologous-made matrix of particulated cartilage and platelet-rich plasma (PACI + PRP) implantation for the treatment of full-thickness chondral defects in sheep., Methods: A full-thickness 8 mm diameter cartilage defect was created in the weight-bearing area of the medial femoral condyle in both knees of 16 sheep. The right knees of all animals were treated with particulated autograft cartilage implantation and platelet-rich plasma, while the left knees were injected with Ringer's lactate solution or hyaluronic acid. The sheep were killed 9 or 18 months after surgery. Macroscopic evaluations were performed using three different scoring systems, and histopathological evaluations were performed using a modified scoring system based on different scoring systems., Results: The PACI + PRP groups showed statistically significant differences in the percentage of defect repair and chondrocytes in the newly formed cartilage tissue at 18 months compared to 9 months., Conclusions: The results suggest that macroscopic appearance, histological structure and chondrocyte repair were improved when using PACI + PRP treatment for chondral defects, producing an outcome similar to the surrounding healthy cartilage. PACI + PRP is a totally autologous, easy, and unexpensive treatment that can be performed in one-step procedure and is useful as a therapeutic option for knee chondral defects., (© 2023. The Author(s).)

Müller-Weiss disease (MWD) is the result of a dysplasia of the tarsal navicular bone. Over the adult years, the dysplastic bone leads to the development of an asymmetric talonavicular arthritis with the talar head shifting laterally and plantarly, thus driving the subtalar joint into varus. From a diagnostic point of view, the condition may be difficult to differentiate from an avascular necrosis or even a stress fracture of the navicular, but fragmentation is the result of a mechanical impairment rather than a biological dysfunction.Standardized weight-bearing radiographs (anteroposterior and lateral views) of both feet are usually enough to diagnose MWD. Other imaging modalities such as multi-detector computed tomography and magnetic resonance imaging in early cases for the differential diagnosis can add additional details on the amount of cartilage affected, bone stock, fragmentation, and associated soft tissue injuries. Failure to identify patients with paradoxical flatfeet varus may lead to an incorrect diagnosis and management. Conservative treatment with the use of rigid insoles is effective in most patients. A calcaneal osteotomy seems to be a satisfactory treatment for patients who fail to respond to conservative measures and a good alternative to the different types of peri-navicular fusions. Weight-bearing radiographs are also useful to identify postoperative changes., Competing Interests: None declared., (Thieme. All rights reserved.)

We investigated whether baseline sagittal-plane ankle, knee, and hip contribution to the total support moment (TSM) are each associated with baseline-to-2-year tibiofemoral and patellofemoral tissue damage worsening in adults with knee osteoarthritis. Ambulatory lower-limb kinetics were captured and computed. TSM is the sum of ankle, knee, and hip extensor moments at each instant during gait. Ankle, knee, and hip contributions to TSM were computed as joint moments divided by TSM, expressed as percentages. Participants underwent MRI of both knees at baseline and 2 years later. Logistic regression models assessed associations of baseline ankle contribution to TSM with baseline-to-2-year cartilage damage and bone marrow lesion worsening, adjusted for age, sex, BMI, gait speed, disease severity, and pain. We used similar analytic approaches for knee and hip contributions to TSM. Sample included 391 knees from 204 persons (age[SD]: 64[10] years; 76.5% women). Greater ankle contribution may be associated with increased odds of tibiofemoral cartilage damage worsening (OR = 2.38; 95% CI: 1.02-5.57) and decreased odds of patellofemoral bone marrow lesion worsening (OR = 0.14; 95% CI: 0.03-0.73). The ORs for greater knee contribution were in the protective range for tibiofemoral compartment and in the deleterious range for patellofemoral. Greater hip contribution may be associated with increased odds of tibiofemoral worsening (OR = 2.71; 95% CI: 1.17-6.30). Greater ankle contribution to TSM may be associated with baseline-to-2-year tibiofemoral worsening, but patellofemoral tissue preservation. Conversely, greater knee contribution may be associated with patellofemoral worsening, but tibiofemoral preservation. Preliminary findings illustrate potential challenges in developing biomechanical interventions beneficial to both tibiofemoral and patellofemoral compartments., (© 2022 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Background: Debate continues as to whether surgical treatment with chondral-regeneration devices is superior to microfracture for focal articular cartilage defects in the knee., Purpose: To evaluate the superiority of scaffold-associated chondral-regeneration procedures over microfracture by assessing: (1) Patient-reported outcomes; (2) Intervention failure; (3) Histological quality of cartilage repair., Study Design: A three-concept keyword search strategy was designed, in accordance with PRISMA guidelines: (i) knee (ii) microfracture (iii) scaffold. Four databases (Ovid Medline, Embase, CINAHL and Scopus) were searched for comparative clinical trials (Level I-III evidence). Critical appraisal used two Cochrane tools: the Risk of Bias tool (RoB2) for randomized control trials and the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I). Study heterogeneity permitted qualitative analysis with the exception of three patient-reported scores, for which a meta-analysis was performed., Results: Twenty-one studies were identified (1699 patients, age range 18-66 years): ten randomized control trials and eleven non-randomized study interventions. Meta-analyses of the International Knee Documentation Committee (IKDC), Knee Injury And Osteoarthritis Outcome Score (KOOS) for pain and activities of daily living, and Lysholm score demonstrated statistically significant improvement in outcomes for scaffold procedures compared to microfracture at two years. No statistical difference was seen at five years., Conclusion: Despite the limitations of study heterogeneity, scaffold-associated procedures appear to be superior to MF in terms of patient-reported outcomes at two years though similar at five years. Future evaluation would benefit from studies using validated clinical scoring systems, reporting failure, adverse events and long-term clinical follow up to determine technique safety and superiority., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.)

Objective: Articular cartilage defect causes joint pain and finally progresses to osteoarthritis. Although the subchondral bone condition affects clinical outcomes of cartilage defects, the natural course of changes in subchondral bone and associated pain in full-thickness cartilage defects remain unknown. Therefore, we investigated the natural course of histological changes in subchondral bone and joint pain in cartilage defects using a rat model., Design: Full-thickness cartilage defects were created at the medial femoral condyle of 10-week-old male Sprague-Dawley rats. Rats were sacrificed at 3, 7, 14, 28, and 56 days postoperatively, and histological including immunohistochemistry and tartrate-resistant acid phosphatase (TRAP) staining and micro-computed tomography (μCT) analyses of their knees were performed. Pain was evaluated using behavioral analysis and immunofluorescence staining of the dorsal root ganglion (DRG)., Results: The contour of the subchondral bone plate was maintained until day 3, but it was absorbed just under the cartilage defect from day 7 to 14. Starting on day 28, sclerotic changes surrounding the bone absorption area were detected. In the subchondral bone, the number of TRAP-positive cells peaked on day 14. Osteocalcin-positive cells were observed at 7 days, and their number gradually increased till day 56. Behavioral analysis showed that the total distance and the number of getting up by hind legs decreased on day 14. The number of calcitonin gene-related peptide-positive fibers in the DRG increased and was the highest on day 14., Conclusions: The subchondral bone condition under cartilage defects dynamically changes from bone resorption to sclerosis and is related to pain level.

Background: Intra-articular injection of C-type natriuretic peptide (CNP) at the acute inflammatory stage suppressed fibrotic changes in the infrapatellar fat pad (IFP), articular cartilage degeneration, and persistent pain in a monoiodoacetic acid (MIA)-induced rat knee arthritis model. In this study, we administered CNP during the inflammation subsiding period to evaluate CNP effectiveness in knees with osteoarthritis (OA) pathology., Methods: 20 male Wistar rats were randomly divided into two groups. The rats received an intra-articular injection of MIA solution in the right knee to induce inflammation-induced joint degeneration. One group subsequently received an intra-articular CNP injection for six consecutive days from day 8, whereas another group received vehicle solution. Pain avoidance behavior tests and histological analyses were conducted to examine the therapeutic effects of CNP., Results: The incapacitance test indicated that the percent weight on the ipsilateral limb decreased after MIA injection by day 4 and continued to decrease until the end of the experiment in the vehicle group, suggesting persistent pain in the knee. Intra-articular injection of CNP reversed the weight-bearing ratio on day 19. Histological evaluation showed that the CNP group had more residual fat tissue in the IFP and fewer calcitonin gene-related peptide-positive nerve endings compared to the vehicle group. CNP could not reverse articular cartilage degeneration., Conclusions: Intra-articular injection of CNP after the IFP fibrosis onset had no significant effect on OA severity and extent. Nevertheless, CNP might be utilized therapeutically for OA treatment since it can alleviate persistent knee pain and inhibit structural changes in residual fat tissue.

Objective: Metabolic osteoarthritis (OA) is one of the proposed clinical phenotypes defined by the existence of metabolic syndrome (MetS). This study aimed to (1) investigate whether MetS and its components are associated with progression of knee OA magnetic resonance imaging (MRI) features, and (2) to evaluate the interaction of MetS with menopause and progression of MRI features., Method: 682 women from the Rotterdam Study who participated in a sub-study with knee MRI data available and 5-year follow-up were included. Tibiofemoral (TF) and patellofemoral (PF) OA features were assessed with the MRI Osteoarthritis Knee Score. MetS was quantified by the MetS severity Z-score. Generalized estimating equations were used to evaluate associations between MetS and menopausal transition and progression of MRI features., Results: MetS severity at baseline was associated with progression of osteophytes in all compartments, bone marrow lesions (BMLs) in the PF compartment, and cartilage defects in the medial TF compartment. Waist circumference was associated with progression of osteophytes in all compartments and cartilage defects in the medial TF compartment. High-density lipoprotein (HDL)-cholesterol levels were associated with progression of osteophytes in the medial and lateral TF compartment and glucose levels with osteophytes in the PF and medial TF compartment. No interactions were found between MetS with menopausal transition and MRI features., Conclusion: Women with higher MetS severity at baseline showed progression of osteophytes, BMLs, and cartilage defects, indicating more structural knee OA progression after 5 years. Further studies are required to understand whether targeting MetS components may prevent the progression of structural knee OA in women., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To determine the relationship between the severity of the tear gap resulting from medial meniscus posterior root (MMPR) tear and medial meniscal extrusion, cartilage, bone, and ligament lesions on MRI., Methods: A total of 133 patients with MMPR tear were retrospectively evaluated. The patients were divided into two groups according to the tear gap width as minor (≤ 4 mm) and widely (4 mm<) displaced. Medial meniscal extrusion and medial compartmental chondromalacia, bone and ligament lesions were analyzed., Results: There were 61 patients (56 women and 5 men) in the minor displaced group (mean age: 56.3 years, range: 29-82 years) and 72 patients (59 women, 13 men) in the widely displaced group (mean age: 53.2 years, range: 20-86 years). There was no significant difference in terms of age and sex (p = 0.31 and p = 0.09, respectively). The mean absolute extrusion was 3.51 mm (range: 1.5-5 mm) in the minor displaced group and 4.52 mm (range: 2.4-7.2 mm) in the widely displaced group (p < 0.001). High-grade medial femoral condylar chondromalacia was more common in the widely displaced group (p = 0.002). Osteophyte, bone marrow edema, and subchondral cyst in the medial compartment, and ligament injury were higher in the widely displaced group, but were not statistically significant (p > 0.05)., Conclusion: The amount of medial meniscal extrusion and the prevalence of high-grade medial femoral condylar chondromalacia were found to be significantly more in patients with wider tear gap. Determining the amount of tear gap in the evaluation of root ligament tears on MRI is important to predict knee joint internal derangement., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

To investigate and compare the values of 3.0 T MRI T1, T2 and T2* mapping quantification techniques in evaluating cartilage degeneration of the shoulder joint. This study included 123 shoulder joints of 119 patients, which were scanned in 3.0 T MRI with axial Fat Suppression Proton Density Weighted Image (FS-PDWI), sagittal fat suppression T2 Weighted Image (FS-T2WI), coronal T1Weighted Image (T1WI), FS-PDWI, cartilage-specific T1, T2 and T2* mapping sequences. Basing on MRI images, the shoulder cartilage was classified into grades 0 1, 2, 3 and 4 according to the International Cartilage Regeneration & Joint Preservation Society (ICRS). The grading of shoulder cartilage was based on MRI images with ICRS as reference, and did not involve arthroscopy or histology.The T1, T2 and T2* relaxation values in the superior, middle and inferior bands of shoulder articular cartilage were measured at all grades, and the differences in various indicators between groups were analyzed and compared using a single-factor ANOVA test. The correlation between T1, T2 and T2* relaxation values and MRI-based grading was analyzed by SPSS software. There were 46 shoulder joints with MRI-based grade 0 in healthy control group (n = 46), while 49 and 28 shoulder joints with grade 1-2 (mild degeneration subgroup) and grade 3-4 (severe degeneration subgroup) in patient group (n = 73), accounting for 63.6% and 36.4%, respectively. The T1, T2 and T2* relaxation values of the superior, middle and inferior bands of shoulder articular cartilage were significantly and positively correlated with the MRI-based grading (P < 0.01). MRI-basedgrading of shoulder cartilage was markedly associated with age (r = 0.766, P < 0.01). With the aggravation of cartilage degeneration, T1, T2 and T2* relaxation values showed an upward trend (all P < 0.01), and T1, T2 and T2* mapping could distinguish cartilage degeneration at all levels (all P < 0.01). The T1, T2 and T2* relaxation values were significantly different between normal group and mild degeneration subgroup, normal group and severe degeneration subgroup, mild degeneration subgroup and severe degeneration subgroup (all P < 0.05). Quantitative T1, T2 and T2* mapping can quantify the degree of shoulder cartilage degeneration. All these MRI mapping quantification techniques can be used as critical supplementary sequences to assess shoulder cartilage degeneration, among which T2 mapping has the highest value., (© 2023. The Author(s).)

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.

Objective: To examine repair tissue formed approximately 15 months after a chondral harvest in the human knee., Design: Sixteen individuals (12 males, 4 females, mean age 36 ± 9 years) underwent a chondral harvest in the trochlea as a pre-requisite for autologous chondrocyte implantation (ACI) treatment. The harvest site was assessed via MRI at 14.3 ± 3.2 months and arthroscopy at 15 ± 3.5 months (using the Oswestry Arthroscopy Score [O-AS] and the International Cartilage Repair Society Arthroscopy Score [ICRS-AS]). Core biopsies (1.8 mm diameter, n = 16) of repair tissue obtained at arthroscopy were assessed histologically (using the ICRS II and OsScore histology scores) and examined via immunohistochemistry for the presence of collagen types I and II., Results: The mean O-AS and ICRS-AS of the repaired harvest sites were 7.2 ± 3.2 and 10.1 ± 3.5, respectively, with 80.3% ± 26% repair fill depth on MRI. The histological quality of the repair tissue formed was variable, with some hyaline cartilage present in 50% of the biopsies; where this occurred, it was associated with a significantly higher ICRS-AS than those with no hyaline cartilage present (median 11 vs. 7.5, P = 0.049). Collagen types I and II were detected in 12/14 and 10/13 biopsies, respectively., Conclusions: We demonstrate good-quality structural repair tissue formed following cartilage harvest in ACI, suggesting this site can be useful to study endogenous cartilage repair in humans. The trochlea is less commonly affected by osteoarthritis; therefore, location may be critical for spontaneous repair. Understanding the mechanisms and factors influencing this could improve future treatments for cartilage defects.

Objective: To assess the association of worsening of magnetic resonance imaging (MRI) semi-quantitative (SQ) tissue features with concurrent change in quantitative (Q) cartilage thickness measurements over 24 months within the Foundation for the National Institutes of Health (FNIH) Biomarker Consortium study., Methods: In all, 599 participants were included. SQ assessment included cartilage damage, meniscal extrusion and damage, osteophytes, bone marrow lesions (BMLs), and effusion- and Hoffa-synovitis. Change in medial compartment Q cartilage thickness was stratified by concurrent ipsicompartmental SQ changes. Between-group comparisons were performed using analysis of covariance (ANCOVA) with adjustment for age, sex, and body mass index (BMI). Results were presented as adjusted mean difference., Results: Knees with any increase in SQ cartilage scores in the medial compartment ( n = 268) showed more Q cartilage loss compared to knees that remained stable (mean adjusted difference [MAD] = -0.16 mm, 95% confidence interval [CI]: [-0.19, -0.13] mm). Knees with any increase in meniscal extrusion in the medial compartment (n = 98) showed more Q cartilage loss than knees without (MAD = -0.18 mm, 95% CI: [-0.22, -0.14] mm. Comparable findings were seen for meniscal damage worsening. Regarding BMLs, an increase by one subregion resulted in a MAD of Q cartilage loss of -0.10 mm, 95% CI: [-0.14, -0.06] mm, while this effect almost tripled for change in two or more subregions. Increase in either effusion- and/or Hoffa-synovitis by one grade resulted in a MAD of -0.07 mm, 95% CI: [-0.10, -0.03] mm., Conclusion: Worsening of SQ cartilage damage, meniscal extrusion and damage, number of subregions affected by BML, maximum size of BMLs and worsening of effusion- and/or Hoffa synovitis is associated with increased Q cartilage loss.