Patrick X. Bradley , Sophia Y. Kim-Wang , Brooke S. Blaisdell , Alexie D. Riofrio , Amber T. Collins , Lauren N. Heckelman , Eziamaka C. Obunadike , Margaret R. Widmyer , Chinmay S. Paranjape , Bryan S. Crook , Nimit K. Lad , Edward G. Sutter , Brian P. Mann , Charles E. Spritzer , Louis E. DeFrate
{"title":"Tibiofemoral cartilage strain and recovery following a 3-mile run measured using deep learning segmentation of bone and cartilage","authors":"Patrick X. Bradley , Sophia Y. Kim-Wang , Brooke S. Blaisdell , Alexie D. Riofrio , Amber T. Collins , Lauren N. Heckelman , Eziamaka C. Obunadike , Margaret R. Widmyer , Chinmay S. Paranjape , Bryan S. Crook , Nimit K. Lad , Edward G. Sutter , Brian P. Mann , Charles E. Spritzer , Louis E. DeFrate","doi":"10.1016/j.ocarto.2024.100556","DOIUrl":"10.1016/j.ocarto.2024.100556","url":null,"abstract":"<div><h3>Objective</h3><div>We sought to measure the deformation of tibiofemoral cartilage immediately following a 3-mile treadmill run, as well as the recovery of cartilage thickness the following day. To enable these measurements, we developed and validated deep learning models to automate tibiofemoral cartilage and bone segmentation from double-echo steady-state magnetic resonance imaging (MRI) scans.</div></div><div><h3>Design</h3><div>Eight asymptomatic male participants arrived at 7 a.m., rested supine for 45 min, underwent pre-exercise MRI, ran 3 miles on a treadmill, and finally underwent post-exercise MRI. To assess whether cartilage recovered to its baseline thickness, participants returned the following morning at 7 a.m., rested supine for 45 min, and underwent a final MRI session. These images were used to generate 3D models of the tibia, femur, and cartilage surfaces at each time point. Site-specific tibial and femoral cartilage thicknesses were measured from each 3D model. To aid in these measurements, deep learning segmentation models were developed.</div></div><div><h3>Results</h3><div>All trained deep learning models demonstrated repeatability within 0.03 mm or approximately 1 % of cartilage thickness. The 3-mile run induced mean compressive strains of 5.4 % (95 % CI = 4.1 to 6.7) and 2.3 % (95 % CI = 0.6 to 4.0) for the tibial and femoral cartilage, respectively. Furthermore, both tibial and femoral cartilage thicknesses returned to within 1 % of baseline thickness the following day.</div></div><div><h3>Conclusions</h3><div>The 3-mile treadmill run induced a significant decrease in both tibial and femoral cartilage thickness; however, this was largely ameliorated the following morning.</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"7 1","pages":"Article 100556"},"PeriodicalIF":0.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11720442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kenneth Chen , Christoph Stotter , Christopher Lepenik , Thomas Klestil , Christoph Salzlechner , Stefan Nehrer
{"title":"Frontal plane mechanical leg alignment estimation from knee x-rays using deep learning","authors":"Kenneth Chen , Christoph Stotter , Christopher Lepenik , Thomas Klestil , Christoph Salzlechner , Stefan Nehrer","doi":"10.1016/j.ocarto.2024.100551","DOIUrl":"10.1016/j.ocarto.2024.100551","url":null,"abstract":"<div><h3>Objective</h3><div>Lower limb malalignment can complicate symptoms and accelerate knee osteoarthritis (OA), necessitating consideration in study population selection. In this study, we develop and validate a deep learning model that classifies leg alignment as “normal” or “malaligned” from knee antero-posterior (AP)/postero-anterior (PA) radiographs alone, using an adjustable hip-knee-ankle (HKA) angle threshold.</div></div><div><h3>Material and methods</h3><div>We utilized 8878 digital radiographs, including 6181 AP/PA full-leg x-rays (LLRs) and 2697 AP/PA knee x-rays (2292 with positioning frame, 405 without). The model's evaluation involved two steps: In step 1, the model's predictions on knee images cropped from LLRs were compared against the ground truth from the original LLRs. In step 2, the model was tested on knee AP radiographs, using corresponding same-day LLRs as a proxy for ground truth.</div></div><div><h3>Results</h3><div>The model effectively classified alignment, with step one achieving sensitivity and specificity of 0.92 for a threshold of 7.5°, and 0.90 and 0.85 for 5°. For positioning frame images, step two showed a sensitivity of 0.85 and specificity of 0.81 for 7.5°, and 0.79 and 0.74 for 5°. For non-positioning frame images, sensitivity and specificity were 0.91 and 0.83 for 7.5°, and 0.9 and 0.86 for 5°.</div></div><div><h3>Conclusion</h3><div>The model developed in this study accurately classifies lower limb malalignment from AP/PA knee radiographs using adjustable thresholds, offering a practical alternative to LLRs. This can enhance the precision of study population selection and patient management.</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"7 1","pages":"Article 100551"},"PeriodicalIF":0.0,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tolulope Owoyemi , Ibidunni Alonge , Oladapo Adetunji , Emmanuel Ogbu , Adebimpe Ogunbanjo , Simon White , Adewale Adebajo , Christian Mallen , Opeyemi O. Babatunde , Krysia Dziedzic
{"title":"Everyday living with osteoarthritis in the global South: A qualitative focus group inquiry in Nigeria","authors":"Tolulope Owoyemi , Ibidunni Alonge , Oladapo Adetunji , Emmanuel Ogbu , Adebimpe Ogunbanjo , Simon White , Adewale Adebajo , Christian Mallen , Opeyemi O. Babatunde , Krysia Dziedzic","doi":"10.1016/j.ocarto.2024.100555","DOIUrl":"10.1016/j.ocarto.2024.100555","url":null,"abstract":"<div><h3>Objective</h3><div>Africa contributes significantly to the increasing global prevalence (>37 %), unmet need and treatment burden for people with osteoarthritis. Despite this, little research has examined the expressed needs of patients with osteoarthritis (OA) and joint pain in West-Africa. This study aimed to explore lived experiences, expressed needs and current care gaps for people living with osteoarthritis in low-health resource contexts using Nigeria as a case study.</div></div><div><h3>Design</h3><div>Qualitative study using Focus Groups. People aged 45 years and over living with osteoarthritis and joint pain were recruited at local health services or via wide advertisements in the community. Discussions were recorded and transcribed verbatim. Data were analyzed using thematic analysis (inductive approach).</div></div><div><h3>Results</h3><div>Three focus groups were conducted with people living with osteoarthritis (n = 30, age range 45–90 years) across socio-demographic strata. Participants described their experiences of living with osteoarthritis as emotionally, physically, and socio-economically challenging. Four main themes (and 14 sub-themes) were identified. Participants expressed the need for an information and health education campaign and access to appropriate health professionals (especially physiotherapists) for providing support, guidance, and assistance with self-management.</div></div><div><h3>Conclusions</h3><div>The provision of an accessible, and contextually appropriate patient education package, in line with evidence-based recommendations is a critical need for people living with osteoarthritis in Nigeria. This will promote evidence-based care for OA in low-resource settings, empowering patients to self-manage and reducing confusion related to inconsistent advice and mixed messages about cause, healthcare access and OA care.</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"7 1","pages":"Article 100555"},"PeriodicalIF":0.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Camille Fauchon , Marie Binvignat , Francis Berenbaum , Philip G. Conaghan , Roland Peyron , Jérémie Sellam
{"title":"Brain functional imaging contributions in osteoarthritis-related pain: A viewpoint","authors":"Camille Fauchon , Marie Binvignat , Francis Berenbaum , Philip G. Conaghan , Roland Peyron , Jérémie Sellam","doi":"10.1016/j.ocarto.2024.100554","DOIUrl":"10.1016/j.ocarto.2024.100554","url":null,"abstract":"<div><h3>Objective</h3><div>Neuroimaging investigations are critical to provide a more direct assessment of brain disturbances associated with osteoarthritis (OA)-related pain, and to better understand its pathophysiology to develop new treatment strategies. This viewpoint aims to summarize the importance of the brain in OA pain.</div></div><div><h3>Method</h3><div>A European working group on pain in osteoarthritis GO-PAIN (Going Inside Osteoarthritis-related Pain Phenotyping) has been created to work on a global assessment of the OA-related pain. Relevant scientific literature was evaluated, summarized and discussed to expose advances in functional brain alterations related-to OA pain.</div></div><div><h3>Results</h3><div>Findings of neuroimaging studies are highly heterogenous and based on small sample size, but some key brain alterations associated with OA pain can be identified across experiments. A systematic literature review conducted by Hall and colleagues (2023) found lower activity, connectivity, and grey matter volume in the right anterior insula in patients with OA than in healthy controls. Other works also pointed out that activity of specific brain regions could serve as a potential surrogate biomarker, but several limitations and confounding factors needs to be addressed.</div></div><div><h3>Conclusions</h3><div>Brain functional imaging provides opportunities to accurately address an OA-related pain endophenotype. To encompass limitations and fill the gaps from the previous studies, we propose a blueprint for the next 5 years and stimulate ideas for others working in the field.</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"7 1","pages":"Article 100554"},"PeriodicalIF":0.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel F. McWilliams , Mohsen Shahtaheri , Soraya Koushesh , Chitra Joseph , Peter RW. Gowler , Luting Xu , Victoria Chapman , Nidhi Sofat , David A. Walsh
{"title":"The rat osteoarthritis bone score for histological pathology relevant to human bone marrow lesions and pain","authors":"Daniel F. McWilliams , Mohsen Shahtaheri , Soraya Koushesh , Chitra Joseph , Peter RW. Gowler , Luting Xu , Victoria Chapman , Nidhi Sofat , David A. Walsh","doi":"10.1016/j.ocarto.2024.100544","DOIUrl":"10.1016/j.ocarto.2024.100544","url":null,"abstract":"<div><h3>Objectives</h3><div>Histological osteochondral characteristics of inflammation, fibrosis, vascularity, cartilage islands, vessels entering cartilage, thickened trabeculae and cysts are associated with bone marrow lesions (BMLs) in human knee osteoarthritis (OA). We identified and developed a method for scoring comparable pathology in two rat OA knee pain models.</div></div><div><h3>Methods</h3><div>Rats (n = 8–10 per group) were injected with monoiodoacetate (MIA) or saline, or underwent meniscal transection (MNX) or sham surgery. Pain behaviour (weight bearing asymmetry and mechanical hindpaw withdrawal thresholds (PWTs)) were measured and knee samples obtained. Features associated with BMLs were evaluated using haematoxylin and eosin or Safranin-O stained knee sections. Sections were scored for chondropathy, osteophytes, synovitis and with the human OA Bone Score modified for rats (rOABS). rOABS reliability was assessed with intraclass correlation coefficient (ICC), groups were compared using Mann-Whitney U-tests, and associations examined with Spearman's rho.</div></div><div><h3>Results</h3><div>OABS features were more prevalent in each OA pain group than in controls. rOABS displayed good inter-rater reliability (ICC = 0.79). rOABS was higher in each model than controls; MIA 3.0 (2.3–4.0) vs vehicle 0.0 (0.0–0.0), and MNX 4.0 (2.3–4.8) vs sham 0.0 (0.0–0.0), each p < 0.003. rOABS was associated with OA cartilage involvement (rho = 0.69, p < 0.001), osteophyte (rho = 0.61, p < 0.001) and synovial inflammation (rho = 0.76, p < 0.001). Higher rOABS was associated with pain behaviour: weight bearing asymmetry (rho = 0.65, p < 0.001) and PWT (rho = −0.47, p = 0.003).</div></div><div><h3>Conclusions</h3><div>Subchondral pathology in rat OA models resembles human subchondral BMLs. rOABS reliably measured subchondral pathology and was associated with OA structure and pain behaviour.</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"7 1","pages":"Article 100544"},"PeriodicalIF":0.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Slow acting medications for progressive and painful knee osteoarthritis. How do we assess the benefit to risk of these potentially novel therapies?","authors":"Nancy E. Lane, Lee S. Simon, Jeyanesh Tambiah","doi":"10.1016/j.ocarto.2024.100546","DOIUrl":"10.1016/j.ocarto.2024.100546","url":null,"abstract":"","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"7 1","pages":"Article 100546"},"PeriodicalIF":0.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Austin Bell-Hensley , Victor Gustavo Balera Brito , Lei Cai , Jin Liu , Kathryn Feeney , Hongjun Zheng , Audrey McAlinden
{"title":"MicroRNA-181a/b-1 enhances chondroprogenitor anabolism and downregulates aquaporin-9","authors":"Austin Bell-Hensley , Victor Gustavo Balera Brito , Lei Cai , Jin Liu , Kathryn Feeney , Hongjun Zheng , Audrey McAlinden","doi":"10.1016/j.ocarto.2024.100550","DOIUrl":"10.1016/j.ocarto.2024.100550","url":null,"abstract":"<div><h3>Objective</h3><div>Effective osteoarthritis treatments that enhance the anabolic/regenerative capacity of chondrocytes are needed. Studying cartilage development processes may inform us of approaches to control chondrocyte differentiation and anabolism and, ultimately, how to effectively treat OA. MicroRNAs are broad-acting epigenetic regulators known to affect many skeletal processes. Previous reports from our group indicated that miR-181a-1 is upregulated during chondrocyte differentiation. The goal of this study was to determine how the entire miR-181a/b-1 cluster regulates <em>in vitro</em> chondrogenesis.</div></div><div><h3>Design</h3><div>Precursor miR-181a/b-1 was over-expressed in cartilage progenitor cells using lentiviral technology Transduced cartilage progenitor cells were cultured as micromass pellets in hypoxic conditions and stimulated to undergo chondrogenic differentiation for five weeks. Bulk RNA-sequencing and immunostaining was applied to evaluate chondrogenic differentiation and matrix production.</div></div><div><h3>Results</h3><div>Immunostaining of cartilage pellet sections showed that miR-181a/b-1 increased mature type II collagen and decreased expression of the chondroprogenitor type IIA collagen isoform. Bulk RNA-Seq at day 7 of chondrogenesis revealed upregulation of pro-anabolic genes such as <em>COL2A1</em>, <em>COL9A2/3</em>, <em>COL11A2</em> and <em>SNORC</em>. Of the genes significantly downregulated by miR-181a/b-1, aquaporin 9 (<em>AQP9</em>) was the top hit which decreased in expression by over 14-fold. While a predicted target of miR-181a/b, our data showed that this miRNA cluster likely suppresses <em>AQP9</em> via an indirect targeting mechanism.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrate a pro-differentiation/anabolic function for miR-181a/b-1 during <em>in vitro</em> chondrogenesis that may be due, in part, to suppression of <em>AQP9</em>. Future studies are needed to elucidate the role of this membrane channel protein in regulating chondrocyte differentiation and homeostasis.</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"7 1","pages":"Article 100550"},"PeriodicalIF":0.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kosaku Aoyagi , Elias Rivas , Roxanna Shababi , Robert Edwards , Michael LaValley , Julia Lechuga , Vitaly Napadow , Tuhina Neogi
{"title":"Safety and preliminary efficacy of transcutaneous auricular vagus nerve stimulation on chronic knee pain: A pilot trial","authors":"Kosaku Aoyagi , Elias Rivas , Roxanna Shababi , Robert Edwards , Michael LaValley , Julia Lechuga , Vitaly Napadow , Tuhina Neogi","doi":"10.1016/j.ocarto.2024.100545","DOIUrl":"10.1016/j.ocarto.2024.100545","url":null,"abstract":"<div><h3>Objective</h3><div>Transcutaneous auricular vagus nerve stimulation (<strong>tVNS</strong>) may be an innovative treatment for symptoms of knee osteoarthritis (OA) due to possible shared pathological mechanisms between diminished parasympathetic function, central pain mechanisms, and knee pain. Thus, we sought to test the safety and preliminary efficacy of tVNS in people with knee OA.</div></div><div><h3>Design</h3><div>A pilot trial in which participants received a 60-min tVNS was conducted. At baseline, immediately after, and 15 min after tVNS, we assessed knee pain, pressure pain threshold (<strong>PPT</strong>), temporal summation (<strong>TS</strong>), conditioned pain modulation (<strong>CPM</strong>), and high-frequency power of heart rate variability (<strong>HF</strong>). We examined the extent to which these outcome measures changed after tVNS using linear mixed models.</div></div><div><h3>Results</h3><div>30 participants with knee OA were included, and all completed the intervention without any major side effects. Compared to baseline, knee pain was reduced by 1.27 (95 % CI, −1.74, −0.80) immediately after and by 1.87 (−2.33, −1.40) 15 min after tVNS; CPM improved by 0.11 (0.04, 0.19) and 0.07 (−0.01, 0.15); and HF improved by 213.29 (−0.38, 426.96) and 234.17 (20.49, 447.84). PPT and TS were not changed after tVNS.</div></div><div><h3>Conclusions</h3><div>Our preliminary data demonstrated that tVNS may be a safe pain-relieving treatment for people with knee OA. Our findings suggest that improvement of knee pain might be derived from improvement of parasympathetic function and central pain mechanisms as no local therapy was applied. A large study is needed to confirm that tVNS is a novel intervention to ameliorate knee pain in people with knee OA.</div></div><div><h3>Clinical Trial</h3><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (NCT05625178).</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"7 1","pages":"Article 100545"},"PeriodicalIF":0.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Study protocol for the PICASSO trial: A randomized placebo-controlled trial to investigate the efficacy and safety of intraarticular steroid injections and an occupational therapy intervention in painful inflammatory carpometacarpal-1 osteoarthritis","authors":"Marthe Gløersen , Ingvild Kjeken , A.T. Tveter , Amirhossein Kazemi , Joseph Sexton , Krysia Dziedzic , David T. Felson , Tanja A. Stamm , Ali Guermazi , Merete Hermann-Eriksen , M.I. Sæther , Kristine Lundby , E.L. Esperø , Monika Olsen , K.B. Norheim , Edle Berg Fister , Mari Hoff , Jorunn Kvalø Uleberg , Irina Petrovna Midtgard , Therese Andreassen , Trine Amalie Sjøvold","doi":"10.1016/j.ocarto.2024.100542","DOIUrl":"10.1016/j.ocarto.2024.100542","url":null,"abstract":"<div><h3>Objective</h3><div>Our primary objectives are to assess whether intraarticular corticosteroid injections are superior to saline injections with regards to thumb base pain after 4 weeks, and to compare the efficacy of steroid injections, saline injections, and an occupational therapy intervention on thumb base pain after 12 weeks in people with painful inflammatory osteoarthritis (OA) of the first carpometacarpal (CMC-1) joint.</div></div><div><h3>Design</h3><div>In this three-armed, double-blind, randomized multicenter trial, 354 participants with painful inflammatory CMC-1 OA from six Norwegian hospitals are recruited. Participants are randomized 1:1:1 to intraarticular steroid or saline injections in the CMC-1 joint or a multimodal occupational therapy intervention. The primary outcomes are thumb base pain measured on a numeric rating scale (NRS, range: 0–10) after 4 weeks and 12 weeks. Key secondary outcomes include synovitis by Magnetic Resonance Imaging (MRI) after 4 weeks and hand function by the Measure of Activity Performance of the Hand (MAP-Hand) questionnaire after 12 and 24 weeks. Other secondary outcomes are synovitis by clinical examination and ultrasound, measures of pain, function, stiffness, and health-related quality of life, and direct and indirect costs. Adverse events are recorded at each visit. The duration of the randomized controlled trial is 24 weeks, followed by an 80-week open-label observational phase to investigate the long-term efficacy and safety of repeated steroid injections and the occupational therapy intervention.</div></div><div><h3>Conclusions</h3><div>The results from this trial will have important clinical implications and influence future guidelines on OA management of the CMC-1 joint.</div></div><div><h3>Clinical trial registration</h3><div>EU-CT 2023-505254-17-00, NCT06084364.</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"7 1","pages":"Article 100542"},"PeriodicalIF":0.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Josefine E. Naili , Aisha S. Ahmed , Margareta Hedström , Morten Bilde Simonsen , Eva W. Broström , Helena Erlandsson Harris , Ákos Végvári , Cecilia Aulin
{"title":"Proteomic analysis reveals biomarkers associated with performance-based joint function and patient-reported outcomes in knee osteoarthritis","authors":"Josefine E. Naili , Aisha S. Ahmed , Margareta Hedström , Morten Bilde Simonsen , Eva W. Broström , Helena Erlandsson Harris , Ákos Végvári , Cecilia Aulin","doi":"10.1016/j.ocarto.2024.100543","DOIUrl":"10.1016/j.ocarto.2024.100543","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to identify proteins associated with clinical manifestations of knee osteoarthritis (KOA), including performance-based joint function and patient-reported outcome measures (PROM).</div></div><div><h3>Methods</h3><div>This cross-sectional exploratory study included thirteen individuals with KOA and eleven age-matched controls. All participants performed the 30s Single Leg Mini Squat test and 30s Sit-to-Stand test with simultaneous recording of joint kinematics. Individuals with KOA completed the Knee Injury and Osteoarthritis Outcome Score and Forgotten Joint Score-12. Proteins were determined by quantitative mass spectrometry (MS) in plasma. Principal component analysis (PCA), hierarchical cluster analysis (HCA), and Reactome enrichment analysis of the proteome were conducted to identify activated pathways and groups.</div></div><div><h3>Results</h3><div>Performance-based function was worse in individuals with KOA compared to controls, and they reported higher levels of pain. MS analysis identified 82 differentially expressed proteins (DEPs) in KOA (28 upregulated, 54 downregulated of 321 detected proteins). PCA displayed distinct features between KOA and controls, similar to HCA, which distinguished two major clusters. Enrichment analysis displayed platelet activation and degranulation, neutrophil, and extracellular matrix (ECM)-related pathways. From the proteome, 23 DEPs were associated with different aspects of joint function, and 25 DEPs with PROM.</div></div><div><h3>Conclusions</h3><div>Individuals with KOA differed from controls across all three assessment modalities; they presented worse joint function, higher levels of pain, and an altered plasma protein profile. Multiple associations were observed between up- and downregulated DEPs and clinical manifestations. The described study protocol shows promise for performing multivariate analyses for future subgrouping of individuals with KOA.</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"7 1","pages":"Article 100543"},"PeriodicalIF":0.0,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142697425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}