RESUMEN
Osteophytes in osteoarthritis (OA) joints contribute to restriction of joint movement, joint pain, and OA progression, but little is known about osteophyte regulators. Examination of gene expression related to cartilage extracellular matrix, endochondral ossification, and growth factor signaling in articular cartilage and osteophytes obtained from OA knee joints showed that several genes such as COL1A1, VCAN, BGLAP, BMP8B, RUNX2, and SOST were overexpressed in osteophytes compared with articular cartilage. Ratios of mesenchymal stem/progenitor cells, which were characterized by co-expression of CD105 and CD166, were significantly higher in osteophytic cells than articular cells. A three-dimensional culture method for cartilage and osteophyte cells was developed by modification of cultures of self-assembled spheroid cell organoids (spheroids). These spheroids cultured in the media for mesenchymal stem cells containing transforming growth factor-ß3 showed characteristic morphologies and gene expression profiles of articular cartilage and osteophytes, respectively. The effects of IL-1ß, tumor necrosis factor-α, and IL-6 on the spheroids of articular and osteophytic cells were studied. To the best of our knowledge, they provide the first evidence that IL-6 suppresses the spheroid size of osteophytic cells by inducing apoptosis and reducing extracellular matrix molecules. These data show that IL-6 is the suppressor of osteophyte growth and suggest that IL-6 expression and/or activity are implicated in the regulation of osteophyte formation in pathologic joints.
Asunto(s)
Cartílago Articular , Osteoartritis de la Rodilla , Osteoartritis , Osteofito , Humanos , Cartílago Articular/patología , Condrocitos/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Interleucina-6/metabolismo , Articulación de la Rodilla/patología , Osteoartritis/patología , Osteoartritis de la Rodilla/metabolismo , Osteofito/genética , Osteofito/metabolismo , Osteofito/patologíaRESUMEN
OBJECTIVES: The Murphy Roths Large (MRL)/MpJ 'superhealer' mouse strain is protected from post-traumatic osteoarthritis (OA), although no studies have evaluated the microbiome in the context of this protection. This study characterised microbiome differences between MRL and wild-type mice, evaluated microbiome transplantation and OA and investigated microbiome-associated immunophenotypes. METHODS: Cecal material from mixed sex C57BL6/J (B6) or female MRL/MpJ (MRL) was transplanted into B6 and MRL mice, then OA was induced by disruption of the medial meniscus surgery (DMM). In other experiments, transplantation was performed after DMM and transplantation was performed into germ-free mice. Transplanted mice were bred through F2. OARSI, synovitis and osteophyte scores were determined blindly 8 weeks after DMM. 16S microbiome sequencing was performed and metagenomic function was imputed. Immunophenotypes were determined using mass cytometry. RESULTS: MRL-into-B6 transplant prior to DMM showed reduced OA histopathology (OARSI score 70% lower transplant vs B6 control), synovitis (60% reduction) and osteophyte scores (30% reduction) 8 weeks after DMM. When performed 48 hours after DMM, MRL-into-B6 transplant improved OA outcomes but not when performed 1-2 weeks after DMM. Protection was seen in F1 (60% reduction) and F2 progeny (30% reduction). Several cecal microbiome clades were correlated with either better (eg, Lactobacillus, R=-0.32, p=0.02) or worse (eg, Rikenellaceae, R=0.43, p=0.001) OA outcomes. Baseline immunophenotypes associated with MRL-into-B6 transplants and MRL included reduced double-negative T cells and increased CD25+CD4+ T cells. CONCLUSION: The gut microbiome is responsible in part for OA protection in MRL mice and is transferrable by microbiome transplantation. Transplantation induces resting systemic immunophenotyping changes that correlate with OA protection.
Asunto(s)
Cartílago Articular , Microbioma Gastrointestinal , Microbiota , Osteofito , Sinovitis , Ratones , Femenino , Animales , Osteofito/patología , Inmunofenotipificación , Sinovitis/patología , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Cartílago Articular/patologíaRESUMEN
OBJECTIVE: Exercise remains a hallmark treatment for post-traumatic osteoarthritis (PTOA) and may maintain joint homeostasis in part by clearing inflammatory cytokines, cells, and particles. It remains largely unknown whether exercise-induced joint clearance can provide therapeutic relief of PTOA. In this study, we hypothesized that exercise could slow the progression of preclinical PTOA in part by enhancing knee joint clearance. DESIGN: Surgical medial meniscal transection was used to induce PTOA in 3-month-old male Lewis rats. A sham surgery was used as a control. Mild treadmill walking was introduced 3 weeks post-surgery and maintained to 6 weeks post-surgery. Gait and isometric muscle torque were measured at the study endpoint. Near-infrared imaging tracked how exercise altered lymphatic and venous knee joint clearance during discrete time points of PTOA progression. RESULTS: Exercise mitigated joint degradation associated with PTOA by preserving glycosaminoglycan content and reducing osteophyte volume (effect size (95% Confidence Interval (CI)); 1.74 (0.71-2.26)). PTOA increased hind step widths (0.57 (0.18-0.95) cm), but exercise corrected this gait dysfunction (0.54 (0.16-0.93) cm), potentially indicating pain relief. Venous, but not lymphatic, clearance was quicker 1-, 3-, and 6-weeks post-surgery compared to baseline. The mild treadmill walking protocol expedited lymphatic clearance rate in moderate PTOA (3.39 (0.20-6.59) hrs), suggesting exercise may play a critical role in restoring joint homeostasis. CONCLUSIONS: We conclude that mild exercise has the potential to slow disease progression in part by expediting joint clearance in moderate PTOA.
Asunto(s)
Inestabilidad de la Articulación , Osteoartritis de la Rodilla , Condicionamiento Físico Animal , Ratas Endogámicas Lew , Animales , Masculino , Ratas , Condicionamiento Físico Animal/fisiología , Inestabilidad de la Articulación/fisiopatología , Osteoartritis de la Rodilla/fisiopatología , Modelos Animales de Enfermedad , Marcha/fisiología , Articulación de la Rodilla/fisiopatología , Glicosaminoglicanos/metabolismo , Osteoartritis/fisiopatología , Osteoartritis/metabolismo , Osteofito , Progresión de la EnfermedadRESUMEN
OBJECTIVE: People who sustain joint injuries such as anterior cruciate ligament (ACL) rupture often develop post-traumatic osteoarthritis (PTOA). In human patients, ACL injuries are often treated with ACL reconstruction. However, it is still unclear how effective joint restabilization is for reducing the progression of PTOA. The goal of this study was to determine how surgical restabilization of a mouse knee joint following non-invasive ACL injury affects PTOA progression. DESIGN: In this study, 187 mice were subjected to non-invasive ACL injury or no injury. After injury, mice underwent restabilization surgery, sham surgery, or no surgery. Mice were then euthanized on day 14 or day 49 after injury/surgery. Functional analyses were performed at multiple time points to assess voluntary movement, gait, and pain. Knees were analyzed ex vivo with micro-computed tomography, RT-PCR, and whole-joint histology to assess articular cartilage degeneration, synovitis, and osteophyte formation. RESULTS: Both ACL injury and surgery resulted in loss of epiphyseal trabecular bone (-27-32%) and reduced voluntary movement at early time points. Joint restabilization successfully lowered OA score (-78% relative to injured at day 14, p < 0.0001), and synovitis scores (-37% relative to injured at day 14, p = 0.042), and diminished the formation of chondrophytes/osteophytes (-97% relative to injured at day 14, p < 0.001, -78% at day 49, p < 0.001). CONCLUSIONS: This study confirmed that surgical knee restabilization was effective at reducing articular cartilage degeneration and diminishing chondrophyte/osteophyte formation after ACL injury in mice, suggesting that these processes are largely driven by joint instability in this mouse model. However, restabilization was not able to mitigate the early inflammatory response and the loss of epiphyseal trabecular bone, indicating that these processes are independent of joint instability.
Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Progresión de la Enfermedad , Osteoartritis de la Rodilla , Animales , Lesiones del Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior/complicaciones , Ratones , Osteoartritis de la Rodilla/etiología , Osteoartritis de la Rodilla/cirugía , Osteoartritis de la Rodilla/fisiopatología , Reconstrucción del Ligamento Cruzado Anterior/métodos , Cartílago Articular/patología , Microtomografía por Rayos X , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Masculino , Sinovitis/etiología , Sinovitis/cirugía , Osteofito/etiologíaRESUMEN
OBJECTIVE: To systematically review the association of pain, function, and progression in first carpometacarpal (CMC) osteoarthritis (OA) with imaging biomarkers and radiography-based staging. DESIGN: Database searches in PubMed, Embase, and the Cochrane Library, along with citation searching were conducted in accordance with published guidance. Data on the association of imaging with pain, functional status, and disease progression were extracted and synthesized, along with key information on study methodology such as sample sizes, use of control subjects, study design, number of image raters, and blinding. Methodological quality was assessed using National Heart, Lung, and Blood Institute tools. RESULTS: After duplicate removal, a total of 1969 records were screened. Forty-six articles are included in this review, covering a total of 28,202 study participants, 7263 with first CMC OA. Osteophytes were found to be one of the strongest biomarkers for pain across imaging modalities. Radiographic findings alone showed conflicting relationships with pain. However, Kellgren-Lawrence staging showed consistent associations with pain in various studies. Radiographic, sonographic, and MRI findings and staging showed little association to tools evaluating functional status across imaging modalities. The same imaging methods showed limited ability to predict progression of first CMC OA. A major limitation was the heterogeneity in the study base, limiting synthesis of results. CONCLUSION: Imaging findings and radiography-based staging systems generally showed strong associations with pain, but not with functional status or disease progression. More research and improved imaging techniques are needed to help physicians better manage patients with first CMC OA.
Asunto(s)
Articulaciones Carpometacarpianas , Progresión de la Enfermedad , Osteoartritis , Humanos , Articulaciones Carpometacarpianas/diagnóstico por imagen , Articulaciones Carpometacarpianas/fisiopatología , Osteoartritis/diagnóstico por imagen , Osteoartritis/fisiopatología , Estado Funcional , Imagen por Resonancia Magnética , Radiografía , Artralgia/diagnóstico por imagen , Artralgia/fisiopatología , Artralgia/etiología , Dimensión del Dolor , Osteofito/diagnóstico por imagenRESUMEN
BACKGROUND: Several magnetic resonance (MR) techniques have been suggested for radiation-free imaging of osseous structures. PURPOSE: To compare the diagnostic value of ultra-short echo time and gradient echo T1-weighted MRI for the assessment of vertebral pathologies using histology and computed tomography (CT) as the reference standard. STUDY TYPE: Prospective. SUBJECTS: Fifty-nine lumbar vertebral bodies harvested from 20 human cadavers (donor age 73 ± 13 years; 9 male). FIELD STRENGTH/SEQUENCE: Ultra-short echo time sequence optimized for both bone (UTEb) and cartilage (UTEc) imaging and 3D T1-weighted gradient-echo sequence (T1GRE) at 3 T; susceptibility-weighted imaging (SWI) gradient echo sequence at 1.5 T. CT was performed on a dual-layer dual-energy CT scanner using a routine clinical protocol. ASSESSMENT: Histopathology and conventional CT were acquired as standard of reference. Semi-quantitative and quantitative morphological features of degenerative changes of the spines were evaluated by four radiologists independently on CT and MR images independently and blinded to all other information. Features assessed were osteophytes, endplate sclerosis, visualization of cartilaginous endplate, facet joint degeneration, presence of Schmorl's nodes, and vertebral dimensions. Vertebral disorders were assessed by a pathologist on histology. STATISTICAL TESTS: Agreement between T1GRE, SWI, UTEc, and UTEb sequences and CT imaging and histology as standard of reference were assessed using Fleiss' κ and intra-class correlation coefficients, respectively. RESULTS: For the morphological assessment of osteophytes and endplate sclerosis, the overall agreement between SWI, T1GRE, UTEb, and UTEc with the reference standard (histology combined with CT) was moderate to almost perfect for all readers (osteophytes: SWI, κ range: 0.68-0.76; T1GRE: 0.92-1.00; UTEb: 0.92-1.00; UTEc: 0.77-0.85; sclerosis: SWI, κ range: 0.60-0.70; T1GRE: 0.77-0.82; UTEb: 0.81-0.92; UTEc: 0.61-0.71). For the visualization of the cartilaginous endplate, UTEc showed the overall best agreement with the reference standard (histology) for all readers (κ range: 0.85-0.93). DATA CONCLUSIONS: Morphological assessment of vertebral pathologies was feasible and accurate using the MR-based bone imaging sequences compared to CT and histopathology. T1GRE showed the overall best performance for osseous changes and UTEc for the visualization of the cartilaginous endplate. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.
Asunto(s)
Osteofito , Humanos , Masculino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Estudios Prospectivos , Esclerosis , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodos , Vértebras Lumbares/diagnóstico por imagen , Estándares de ReferenciaRESUMEN
BACKGROUND: Osteophyte development is a common characteristic of inflammatory skeletal diseases. Elevated osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) participates in pathological osteogenesis. Integrin-linked kinase (ILK) positively regulates the osteoblastic differentiation of osteoprogenitors, but whether the ILK blockage prevents osteophytes and its potential mechanism is still unknown. Furthermore, the low-dose tumor necrosis factor-α (TNF-α) promotes osteogenic differentiation, but a lack of study reports on the relationship between this cytokine and ILK. OSU-T315 is a small ILK inhibitor, which was used to determine the effect of ILK inhibition on osteogenesis and osteophyte formation. METHODS AND RESULTS: The osteogenesis of BMSCs was evaluated using Alizarin red S staining, alkaline phosphatase, collagen type I alpha 2 chain, and bone gamma-carboxyglutamate protein. The expression and phosphorylation of protein were assessed through western blot. Immunofluorescence was employed to display the distribution of ß-catenin. microCT, hematoxylin-eosin, and safranin O/fast green staining were utilized to observe the osteophyte formation in collagen antibody-induced arthritis mice. We found that ILK blockage significantly declined calcium deposition and osteoblastic markers in a dose- and time-dependent manner. Furthermore, it lowered osteogenesis in the TNF-α-induced inflammatory microenvironment by diminishing the effect of ILK and inactivating the Akt/ GSK-3ß/ ß-catenin pathway. Nuclear ß-catenin was descended by OSU-T315 as well. Finally, the ILK suppression restrained osteophyte formation but not inflammation in vivo. CONCLUSIONS: ILK inhibition lowered osteogenesis in TNF-α-related inflammatory conditions by deactivating the Akt/ GSK-3ß/ ß-catenin pathway. This may be a potential strategy to alleviate osteophyte development in addition to anti-inflammatory treatment.
Asunto(s)
Células Madre Mesenquimatosas , Osteofito , Proteínas Serina-Treonina Quinasas , Ratones , Animales , Osteogénesis , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , beta Catenina/metabolismo , Osteofito/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Células Madre Mesenquimatosas/metabolismo , Diferenciación Celular , Células Cultivadas , Vía de Señalización WntRESUMEN
We report a unique case of cervical anterior spinal artery (ASA) infarction in a 49-year-old male with hypercholesterolemia and sleep apnea. The patient experienced sudden cervical pain, quadriparesis, areflexia, and urinary incontinence after swallowing a large food bolus. Imaging revealed an infarction at the C3-C5 levels and an anomalous right vertebral artery (VA) originating from the thoracic aorta, tightly enclosed between the aorta and a vertebral column with an anterior osteophyte. This aberrant VA was the primary vascular supply to the ASA, with no contribution from the left VA or supreme intercostal arteries. We propose that transient injury to the right VA, induced by compression between the aortic arch, the food bolus, and the osteophyte, led to temporary hypoperfusion of the ASA, causing a watershed ischemic injury in the mid cervical cord's anterior gray matter. The article also provides an in-depth discussion of the developmental and clinical characteristics associated with this rare vascular anomaly.
Asunto(s)
Osteofito , Malformaciones Vasculares , Masculino , Humanos , Persona de Mediana Edad , Arteria Vertebral/diagnóstico por imagen , Arteria Vertebral/anomalías , Cuello , Vértebras Cervicales/diagnóstico por imagen , Infarto/diagnóstico por imagen , Infarto/etiologíaRESUMEN
PURPOSE: This retrospective study aimed to investigate the relationship between intercondylar notch width (ICNW), osteophyte width (OW), and the healing of medial meniscus posterior root tears (MMPRTs) following arthroscopic pullout repair. METHODS: The study included 155 patients diagnosed with MMPRTs who underwent transtibial pullout repair. Meniscal healing status was evaluated on second-look arthroscopy using a previously reported meniscus healing score. Patients were divided into two groups based on this score: the high healing score (group HH, healing score ≥ 8 points) and suboptimal healing score (group SO, healing score ≤ 6 points) groups. Computed tomography scans were performed on patients 1 week postsurgery. ICNW and OW widths were measured and relatively evaluated based on their ratio to the intercondylar distance (ICD), represented as the ICNW/ICD ratio (%) and OW/ICD ratio (%), respectively. Patient-reported outcomes were assessed preoperatively and on second-look arthroscopy using the Knee injury and Osteoarthritis Outcome Score (KOOS) and visual analogue scale (VAS). RESULTS: There were no significant demographic differences between the SO and HH group (n = 35 and 120 patients, respectively). Regarding radiographic measurements, significant differences were observed in the ICNW/ICD ratio (group SO, 24.2%; group HH, 25.2%; p = 0.024), OW (group SO, 2.6 mm; group HH, 2.0 mm; p < 0.001), and OW/ICD ratio (group SO, 3.5%; group HH, 2.7%; p < 0.001). Both groups had similar preoperative clinical scores, but postoperative clinical scores, including KOOS-activities of daily living (group SO, 83.4; group HH, 88.7; p = 0.035) and VAS (group SO, 19.1; group HH, 11.3; p = 0.005), were significantly better in group HH. CONCLUSION: The study suggests that ICNW and OW may play a crucial role in MMPRT healing following arthroscopic pullout repair, as evidenced by the worse clinical outcomes associated with a narrower ICNW and wider OW. These findings highlight the potential significance of ICNW and OW assessments when evaluating meniscal repair indications. LEVEL OF EVIDENCE: Level III.
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Osteofito , Lesiones de Menisco Tibial , Humanos , Meniscos Tibiales/diagnóstico por imagen , Meniscos Tibiales/cirugía , Estudios Retrospectivos , Actividades Cotidianas , Lesiones de Menisco Tibial/cirugía , Artroscopía/métodos , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: There is no established protocol for the low doses of cone-beam computed tomography (CBCT) acquisition and filter application on the diagnosis of condylar morphological alterations. OBJECTIVES: The objective of the study was to evaluate the influence of voxel size and filter application on the diagnosis of condylar morphological alterations in CBCT using an ex vivo model. METHODS: CBCT scans of 36 temporomandibular joints were acquired using OP300 Maxio with voxel sizes of 0.085, 0.125 and 0.280 mm. Three radiologists evaluated the condyles in the CBCT volumes under three filter modes: no filter, '1x' sharpen filter and '2x' sharpen filter. The area under the ROC curve, sensitivity and specificity were calculated by comparing the evaluators' responses with the reference standard and compared among experimental groups using analysis of variance (ANOVA) (α = 5%). RESULTS: The area under the ROC curve, sensitivity and specificity were not affected by voxel size and filter application (p > .05). For osteophyte and flattening, there were more true-positive responses in smaller voxel size. For erosion, the increase of true- and false-positive responses occurred with a larger voxel size. Overall, there was a tendency to decrease true positives for osteophyte and erosion and increase false positives for flattening with the '2x' sharpen filter. CONCLUSIONS: The diagnosis of condylar morphological alterations assessed in this ex vivo analysis is not influenced by the voxel size and the application of the filters. However, attention is needed with the occurrence of false-positive diagnosis with a larger voxel size for erosion and '2x' sharpen filter for flattening.
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Osteofito , Tomografía Computarizada de Haz Cónico Espiral , Humanos , Sensibilidad y Especificidad , Tomografía Computarizada de Haz Cónico/métodos , HuesosRESUMEN
Osteoarthritis (OA) is a common joint disorder characterized by cartilage degeneration, often leading to pain and functional impairment. Minced cartilage implantation (MCI) has emerged as a promising one-step alternative for large cartilage defects. However, the source of chondrocytes for MCI remains a challenge, particularly in advanced OA, as normal cartilage is scarce. We performed in vitro studies to evaluate the feasibility of MCI using osteophyte cartilage, which is present in patients with advanced OA. Osteophyte and articular cartilage samples were obtained from 22 patients who underwent total knee arthroplasty. Chondrocyte migration and proliferation were assessed using cartilage fragment/atelocollagen composites to compare the characteristics and regenerative potential of osteophytes and articular cartilage. Histological analysis revealed differences in cartilage composition between osteophytes and articular cartilage, with higher expression of type X collagen and increased chondrocyte proliferation in the osteophyte cartilage. Gene expression analysis identified distinct gene expression profiles between osteophytes and articular cartilage; the expression levels of COL2A1, ACAN, and SOX9 were not significantly different. Chondrocytes derived from osteophyte cartilage exhibit enhanced proliferation, and glycosaminoglycan production is increased in both osteophytes and articular cartilage. Osteophyte cartilage may serve as a viable alternative source of MCI for treating large cartilage defects in OA.
Asunto(s)
Cartílago Articular , Proliferación Celular , Condrocitos , Osteoartritis , Osteofito , Humanos , Cartílago Articular/metabolismo , Cartílago Articular/patología , Cartílago Articular/cirugía , Condrocitos/metabolismo , Condrocitos/patología , Osteofito/metabolismo , Osteofito/patología , Masculino , Femenino , Anciano , Osteoartritis/metabolismo , Osteoartritis/patología , Osteoartritis/cirugía , Persona de Mediana Edad , Colágeno Tipo II/metabolismo , Colágeno Tipo II/genética , Factor de Transcripción SOX9/metabolismo , Factor de Transcripción SOX9/genética , Células Cultivadas , Movimiento CelularRESUMEN
Angiogenesis and vascular endothelial growth factor (VEGF) are involved in osteoarthritis (OA). We previously reported the inhibitory effect of bevacizumab in a rabbit model of OA. In the current study, we investigated the effects of lenvatinib, an angiogenesis inhibitor targeting the VEGF and fibroblast growth factor receptors, on synovitis, osteophyte formation, and cartilage degeneration in a rabbit OA model. Posttraumatic OA was induced by anterior cruciate ligament transection (ACLT) on one knee of each rabbit. Rabbits were placed into four groups according to the following lenvatinib doses: untreated control (n = 12), L0.3: 0.3 mg/kg/day (n = 15), L1.0: 1.0 mg/kg/day (n = 14), and L3.0: 3.0 mg/kg/day (n = 13) groups. We evaluated limb pain using the weight distribution ratio measured with an incapacitance tester, macroscopic osteophyte formation, and femoral condyle synovium and cartilage histology. For cartilage evaluation, the following distal sites of the femur were evaluated separately: femoral-tibial (FT), femoral-patellar (FP), and femoral corner (between FP and FT). The weight distribution ratio at 12 weeks after surgery was higher in the L0.3 and L1.0 groups than in the control group. Osteophyte formation and synovitis scores were significantly lower in the L0.3, L1.0, and L3.0 groups than in the control group. The Osteoarthritis Research Society International scores of the FT, corner, and FP sites in the L0.3 group were lower than in the control group. The cartilage thickness ratio at the FT and corner sites was significantly lower in the L0.3 group than in the control group. Krenn's grading system of cartilage synovitis showed that all lenvatinib-administered groups had significantly lower scores than the control group. MMP3 expression level in cartilage tissue was significantly lower in the L3.0 group compared with the other three groups. ADAMTS5 expression was lower in the L3.0 group compared with the control and L0.3 groups. Oral administration of lenvatinib inhibited synovitis, osteophyte formation, and cartilage degeneration and reduced pain in a rabbit ACLT model. Lenvatinib is an oral VEGF inhibitor that is easier to administer than other VEGF inhibitors and may have potential as a treatment of posttraumatic OA.
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Osteoartritis de la Rodilla , Compuestos de Fenilurea , Quinolinas , Animales , Conejos , Quinolinas/farmacología , Quinolinas/uso terapéutico , Compuestos de Fenilurea/farmacología , Compuestos de Fenilurea/uso terapéutico , Osteoartritis de la Rodilla/tratamiento farmacológico , Osteoartritis de la Rodilla/patología , Osteoartritis de la Rodilla/etiología , Osteoartritis de la Rodilla/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Modelos Animales de Enfermedad , Masculino , Sinovitis/tratamiento farmacológico , Sinovitis/etiología , Sinovitis/patología , Sinovitis/metabolismo , Cartílago Articular/patología , Cartílago Articular/efectos de los fármacos , Cartílago Articular/metabolismo , Osteofito/tratamiento farmacológico , Osteofito/metabolismo , Osteofito/etiología , Osteofito/patologíaRESUMEN
PURPOSE: The primary goal of this study was to investigate whether superior humeral head osteophyte (SHO) size is associated with rotator cuff insufficiency, including rotator cuff tear (RCT), supraspinatus tendon thickness, and fatty infiltration of the rotator cuff muscles. METHODS: Patients ≥ 18 years who were diagnosed with glenohumeral osteoarthritis were retrospectively reviewed. SHO size was determined by radiograph. MRI measured SHO and RCT presence, type, and size; supraspinatus tendon thickness; and fatty infiltration of rotator cuff musculature. RESULTS: A total of 461 patients were included. Mean SHO size was 1.93 mm on radiographs and 2.13 mm on MRI. Risk ratio for a RCT was 1.14. For each 1-mm increase in SHO size on radiograph, supraspinatus tendon thickness decreased by 0.20 mm. SHO presence was associated with moderate-to-severe fatty infiltration of the supraspinatus with a risk ratio of 3.16. CONCLUSION: SHOs were not associated with RCT but were associated with higher risk of supraspinatus FI and decreased tendon thickness, which could indicate rotator cuff insufficiency. LEVEL OF EVIDENCE: IV.
Asunto(s)
Osteoartritis , Osteofito , Lesiones del Manguito de los Rotadores , Articulación del Hombro , Humanos , Manguito de los Rotadores/diagnóstico por imagen , Cabeza Humeral/diagnóstico por imagen , Osteofito/complicaciones , Osteofito/diagnóstico por imagen , Articulación del Hombro/diagnóstico por imagen , Lesiones del Manguito de los Rotadores/complicaciones , Lesiones del Manguito de los Rotadores/diagnóstico por imagen , Osteoartritis/complicaciones , Osteoartritis/diagnóstico por imagenRESUMEN
Anterior cervical osteophytes are a fairly common X-ray finding in people over 50 years old. Incidence of dysphagia in patients with anterior osteophytes varies from 1% in those aged 40-60 years to 10.6% in patients over 60 years old. The most common causes of anterior cervical hyperosteophytosis causing dysphagia are cervical spondylosis deformans and Forestier disease. We present 2 clinical cases of spondylogenic dysphagia in cervical spondylosis deformans and Forestier disease. The review is devoted to the causes and diagnostic methods for dysphagia caused by anterior cervical osteophytes, as well as surgical options for this pathology. CONCLUSION: Microsurgical resection of anterior osteophytes is an effective method for dysphagia after ineffective therapy for 3 months. Microsurgical osteophytectomy provides stable regression of dysphagia with low recurrence rate.
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Trastornos de Deglución , Hiperostosis Esquelética Difusa Idiopática , Osteofito , Espondilosis , Humanos , Persona de Mediana Edad , Hiperostosis Esquelética Difusa Idiopática/complicaciones , Hiperostosis Esquelética Difusa Idiopática/diagnóstico , Hiperostosis Esquelética Difusa Idiopática/cirugía , Osteofito/complicaciones , Osteofito/diagnóstico por imagen , Osteofito/cirugía , Trastornos de Deglución/diagnóstico por imagen , Trastornos de Deglución/etiología , Trastornos de Deglución/cirugía , Espondilosis/complicaciones , Espondilosis/diagnóstico por imagen , Espondilosis/cirugía , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Vértebras Cervicales/patologíaRESUMEN
OBJECTIVES: Prior studies noted that chondrocyte SIRT6 activity is repressed in older chondrocytes rendering cells susceptible to catabolic signalling events implicated in osteoarthritis (OA). This study aimed to define the effect of Sirt6 deficiency on the development of post-traumatic and age-associated OA in mice. METHODS: Male cartilage-specific Sirt6-deficient mice and Sirt6 intact controls underwent destabilisation of the medial meniscus (DMM) or sham surgery at 16 weeks of age and OA severity was analysed at 6 and 10 weeks postsurgery. Age-associated OA was assessed in mice aged 12 and 18 months of age. OA severity was analysed by micro-CT, histomorphometry and scoring of articular cartilage structure, toluidine blue staining and osteophyte formation. SIRT6-regulated pathways were analysed in human chondrocytes by RNA-sequencing, qRT-PCR and immunoblotting. RESULTS: Sirt6-deficient mice displayed enhanced DMM-induced OA severity and accelerated age-associated OA when compared with controls, characterised by increased cartilage damage, osteophyte formation and subchondral bone sclerosis. In chondrocytes, RNA-sequencing revealed that SIRT6 depletion significantly repressed cartilage extracellular matrix (eg, COL2A1) and anabolic growth factor (eg, insulin-like growth factor-1 (IGF-1)) gene expression. Gain-of-function and loss-of-function studies in chondrocytes demonstrated that SIRT6 depletion attenuated, whereas adenoviral overexpression or MDL-800-induced SIRT6 activation promoted IGF-1 signalling by increasing Aktser473 phosphorylation. CONCLUSIONS: SIRT6 deficiency increases post-traumatic and age-associated OA severity in vivo. SIRT6 profoundly regulated the pro-anabolic and pro-survival IGF-1/Akt signalling pathway and suggests that preserving the SIRT6/IGF-1/Akt axis may be necessary to protect cartilage from injury-associated or age-associated OA. Targeted therapies aimed at increasing SIRT6 function could represent a novel strategy to slow or stop OA.
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Cartílago Articular , Osteoartritis , Osteofito , Sirtuinas , Masculino , Animales , Ratones , Humanos , Anciano , Factor I del Crecimiento Similar a la Insulina/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Osteoartritis/genética , Osteoartritis/metabolismo , Condrocitos/metabolismo , Cartílago Articular/metabolismo , ARN/metabolismo , Sirtuinas/genética , Sirtuinas/metabolismo , Modelos Animales de EnfermedadRESUMEN
OBJECTIVE: To study potential surrogate outcomes for osteoarthritis (OA) incidence by evaluating the association of short-term changes in clinical and imaging biomarkers with long-term clinical knee OA incidence. DESIGN: Middle-aged women with overweight/obesity, but free of knee symptoms were recruited through their general practitioners. At baseline, after 2.5 years, and after 6.5 years, questionnaires, physical examination, radiographs, and Magnetic resonance imaging (MRI) scans were obtained. The percentage of knees with a minimal clinically important difference for knee pain severity, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain/stiffness/function, and joint space narrowing, and of those with progression/regression of medial knee alignment, chronic knee pain, radiographic osteophytes, and cartilage defects, bone marrow lesions, osteophytes, and effusion/synovitis on MRI were determined. For each of these potential surrogate outcomes with ≥10% improvement or progression in the population over 2.5 years, the association with incident clinical knee OA, defined using the combined ACR-criteria, after 6.5 years was determined. RESULTS: Most pre-defined potential surrogate outcomes showed ≥10% change in the population over 2.5 years, but only worsening of TF cartilage defects, worsening of TF osteophytes on MRI, and an increase in pain severity were significantly associated with greater clinical knee OA incidence after 6.5 years. These potential surrogate outcomes had high specificity and negative predictive value (89-91%) and low sensitivity and positive predictive value (20-28%) CONCLUSIONS: Worsening of TF cartilage defects and TF osteophytes on MRI, and increased pain severity could be seen as surrogate outcomes for long-term OA incidence. However, higher positive predictive values seem warranted for the applicability of these factors in future preventive trials.
Asunto(s)
Enfermedades Óseas , Enfermedades de los Cartílagos , Cartílago Articular , Osteoartritis de la Rodilla , Osteofito , Persona de Mediana Edad , Humanos , Femenino , Osteofito/patología , Cartílago Articular/patología , Articulación de la Rodilla/patología , Imagen por Resonancia Magnética/métodos , Dolor/patología , Enfermedades de los Cartílagos/patología , Enfermedades Óseas/patología , Progresión de la EnfermedadRESUMEN
OBJECTIVE: To determine if baseline biomarkers are associated with longitudinal changes in the worsening of disc space narrowing (DSN), vertebral osteophytes (OST), and low back pain (LBP). DESIGN: Paired baseline (2003-2004) and follow-up (2006-2010) lumbar spine radiographs from the Johnston County Osteoarthritis Project were graded for severity of DSN and OST. LBP severity was self-reported. Concentrations of analytes (cytokines, proteoglycans, and neuropeptides) were quantified by immunoassay. Pressure-pain threshold (PPT), a marker of sensitivity to pressure pain, was measured with a standard dolorimeter. Binary logistic regression models were used to estimate odd ratios (OR) and 95% confidence intervals (CI) of biomarker levels with DSN, OST, or LBP. Interactions were tested between biomarker levels and the number of affected lumbar spine levels or LBP. RESULTS: We included participants (n = 723) with biospecimens, PPT, and paired lumbar spine radiographic data. Baseline Lumican, a proteoglycan reflective of extracellular matrix changes, was associated with longitudinal changes in DSN worsening (OR = 3.19 [95% CI 1.22, 8.01]). Baseline brain-derived neuropathic factor, a neuropeptide, (OR = 1.80 [95% CI 1.03, 3.16]) was associated with longitudinal changes in OST worsening, which may reflect osteoclast genesis. Baseline hyaluronic acid (OR = 1.31 [95% CI 1.01, 1.71]), indicative of systemic inflammation, and PPT (OR = 1.56 [95% CI 1.02, 2.31]) were associated with longitudinal increases in LBP severity. CONCLUSION: These findings suggest that baseline biomarkers are associated with longitudinal changes occurring in structures of the lumbar spine (DSN vs OST). Markers of inflammation and perceived pressure pain sensitivity were associated with longitudinal worsening of LBP.
Asunto(s)
Degeneración del Disco Intervertebral , Dolor de la Región Lumbar , Osteoartritis de la Columna Vertebral , Osteoartritis , Osteofito , Humanos , Dolor de la Región Lumbar/etiología , Osteoartritis/complicaciones , Degeneración del Disco Intervertebral/complicaciones , Degeneración del Disco Intervertebral/diagnóstico por imagen , Osteoartritis de la Columna Vertebral/complicaciones , Biomarcadores , Vértebras Lumbares/diagnóstico por imagen , Osteofito/diagnóstico por imagen , Osteofito/complicaciones , Inflamación/complicacionesRESUMEN
OBJECTIVE: To explore the diagnostic performance of routine magnetic resonance imaging (MRI) for the cross-sectional assessment of osteophytes (OPs) in all three knee compartments using computed tomography (CT) as a reference standard. METHODS: The Strontium Ranelate Efficacy in Knee Osteoarthritis (SEKOIA) trial explored the effect of 3 years of treatment with strontium ranelate in patients with primary knee OA. OPs were scored for the baseline visit only using a modified MRI Osteoarthritis Knee Score (MOAKS) scoring system in the patellofemoral (PFJ), the medial tibiofemoral (TFJ) and the lateral TFJ. Size was assessed from 0 to 3 in 18 locations. Descriptive statistics were used to describe differences in ordinal grading between CT and MRI. In addition, weighted-kappa statistics were employed to assess agreement between scoring using the two methods. Sensitivity, specificity, positive predictive value and negative predictive value as well as area under the curve (AUC) measures of diagnostic performance were employed using CT as the reference standard. RESULTS: Included were 74 patients with available MRI and CT data. Mean age was 62.9 ± 7.5 years. Altogether 1,332 locations were evaluated. For the PFJ, MRI detected 141 (72%) of 197 CT-defined OPs with a w-kappa of 0.58 (95% CI [0.52-0.65]). In the medial TFJ, MRI detected 178 (81%) of 219 CT-OPs with a w-kappa of 0.58 (95% CI [0.51-0.64]). For the lateral compartment these numbers were 84 (70%) of 120 CT-OPs with a w-kappa of 0.58 (95% CI [0.50-0.66]). CONCLUSION: MRI underestimates presence of osteophytes in all three knee compartments. CT may be helpful particularly regarding assessment of small osteophytes particularly in early disease.
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Osteoartritis de la Rodilla , Osteofito , Humanos , Persona de Mediana Edad , Anciano , Radiografía , Osteofito/diagnóstico por imagen , Estudios Transversales , Imagen por Resonancia Magnética/métodos , Articulación de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Estándares de ReferenciaRESUMEN
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.
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Enfermedades de los Cartílagos , Síndrome Metabólico , Osteoartritis de la Rodilla , Osteofito , Femenino , Humanos , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/patología , Síndrome Metabólico/complicaciones , Síndrome Metabólico/diagnóstico por imagen , Osteofito/patología , Progresión de la Enfermedad , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/patología , Imagen por Resonancia Magnética/métodos , Enfermedades de los Cartílagos/patologíaRESUMEN
OBJECTIVE: To compare sacroiliac joint (SIJ) lesions on MRI in women with versus without axial spondyloarthritis (ax-SpA) and establish an algorithm to determine whether such lesions are due to ax-SpA. METHODS: This retrospective comparative study assessed bone marrow edema (BME), sclerosis, erosions, osteophytes, and ankylosis at the SIJ in two groups of women, one with and another without ax-SpA. Sensitivity and specificity were calculated for combinations/characteristics of lesions, using rheumatologists' assessment with assessment of spondyloarthritis international society (ASAS) criteria as the gold standard for diagnosis of ax-SpA. RESULTS: Compared to women without ax-SpA, women with ax-SpA had more BME (61% vs 17%, p < 0.001), sclerosis (40% vs 22%, p < 0.001), erosions (35% vs 5%, p < 0.001), and ankylosis (2% vs 0%, p = 0.007), but less osteophytes (5% vs 33%, p < 0.001). The ASAS MRI criteria yielded 59% sensitivity and 88% specificity, while a new algorithm achieved 56% sensitivity and 95% specificity using the following criteria: no osteophytes at the SIJ and either (i) BME at the SIJ with at least one dimension ≥ 8 mm or (ii) at least one erosion at the SIJ. CONCLUSIONS: We recommend the following pragmatic algorithm for MRI diagnosis of ax-SpA in women: no osteophytes at the SIJ and either (i) BME at the SIJ with at least one dimension ≥ 8 mm or (ii) at least one erosion at the SIJ. The false positive rate when using the new algorithm (3.3%) is less than half than when using the ASAS MRI criteria (7.7%); thus, its application in clinical practice could reduce overdiagnosis and prevent overtreatment of ax-SpA. CLINICAL RELEVANCE STATEMENT: The developed algorithm has a false-positive rate that is less than half than when using the ASAS MRI criteria (3.3% vs 7.7%), thus its application in clinical practice could reduce overdiagnosis and prevent overtreatment of axial spondyloarthritis. KEY POINTS: ⢠Compared to women without axial spondyloarthritis (ax-SpA), women with ax-SpA had a significantly higher prevalence of bone marrow edema (BME), sclerosis, erosions, and ankylosis, but a significantly lower prevalence of osteophytes. ⢠A new algorithm for positive ax-SpA based on sacroiliac joint MRI was developed: no osteophytes at the sacroiliac joint (SIJ) and either (i) BME at the SIJ with at least one dimension ≥ 8 mm or (ii) at least one erosion at the SIJ. ⢠We recommend this new algorithm for diagnosis of ax-SpA in women, as it has a significantly better specificity than the assessment of spondyloarthritis international society (ASAS) MRI criteria and less than half the false positive rate; thus, its application in clinical practice could reduce overdiagnosis and prevent overtreatment of ax-SpA.