Therapeutic Advances in Musculoskeletal Disease最新文献

{"title":"Anti-sclerostin antibodies: a new frontier in fragility fractures treatment.","authors":"Giovanni Iolascon,&nbsp;Sara Liguori,&nbsp;Marco Paoletta,&nbsp;Giuseppe Toro,&nbsp;Antimo Moretti","doi":"10.1177/1759720X231197094","DOIUrl":"https://doi.org/10.1177/1759720X231197094","url":null,"abstract":"<p><p>Bone fragility is the determinant of the increased risk of minimal trauma fracture and must be treated with a multimodal approach that includes pharmacological therapy, physical exercise, and adequate nutrition. Pharmacological therapy, to date based on the administration of antiresorptive drugs, such as bisphosphonates and denosumab, or osteoanabolic drugs, such as teriparatide and abaloparatide, has shown to be effective in reducing the risk of fracture in osteoporotic patients. In the context of the cellular and molecular mechanisms that regulate bone metabolism, the discovery of the Wnt signaling pathway and its role in bone tissue homeostasis has allowed the identification of sclerostin as an inhibitor of osteoblastic activity and simultaneously as a stimulator of osteoclastic activity. Therefore, the use of a monoclonal antibody, romosozumab, against this protein has been tested as a potential drug with a dual action, stimulating bone neo-apposition and inhibiting bone resorption. The efficacy of romosozumab has been demonstrated in numerous clinical trials against both placebo and other drugs commonly used in the treatment of patients affected by osteoporosis. The advantages of this drug lie above all in its rapid action which makes it particularly suitable in clinical situations where it is necessary to improve bone strength very quickly due to the imminent risk of fragility fracture. Clinical studies and guidelines suggest romosozumab as an initial drug in an ideal sequential approach from osteoanabolic to antiresorptive drugs. Some aspects of cardiovascular safety remain to be fully investigated, therefore its use in osteoporotic patients at high cardiovascular risk should be avoided until further data become available.</p>","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"15 ","pages":"1759720X231197094"},"PeriodicalIF":4.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6b/b2/10.1177_1759720X231197094.PMC10492476.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10222217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medication holidays in osteoporosis: evidence-based recommendations from the Italian guidelines on 'Diagnosis, risk stratification, and continuity of care of fragility fractures' based on a systematic literature review.","authors":"Silvia Migliaccio,&nbsp;Antimo Moretti,&nbsp;Annalisa Biffi,&nbsp;Raffaella Ronco,&nbsp;Gloria Porcu,&nbsp;Giovanni Adami,&nbsp;Rosaria Alvaro,&nbsp;Riccardo Bogini,&nbsp;Achille Patrizio Caputi,&nbsp;Luisella Cianferotti,&nbsp;Bruno Frediani,&nbsp;Davide Gatti,&nbsp;Stefano Gonnelli,&nbsp;Andrea Lenzi,&nbsp;Salvatore Leone,&nbsp;Tiziana Nicoletti,&nbsp;Marco Paoletta,&nbsp;Annalisa Pennini,&nbsp;Eleonora Piccirilli,&nbsp;Raffaella Michieli,&nbsp;Umberto Tarantino,&nbsp;Maurizio Rossini,&nbsp;Giovanni Corrao,&nbsp;Maria Luisa Brandi,&nbsp;Giovanni Iolascon","doi":"10.1177/1759720X231177110","DOIUrl":"https://doi.org/10.1177/1759720X231177110","url":null,"abstract":"<p><strong>Background: </strong>Noncommunicable, chronic diseases need pharmacological interventions for long periods or even throughout life. The temporary or permanent cessation of medication for a specific period, known as a 'medication holiday,' should be planned by healthcare professionals.</p><p><strong>Objectives: </strong>We evaluated the association between continuity (adherence or persistence) of treatment and several outcomes in patients with fragility fractures in the context of the development of the Italian Guidelines.</p><p><strong>Design: </strong>Systematic review.</p><p><strong>Data sources and methods: </strong>We systematically searched PubMed, Embase, and the Cochrane Library up to November 2020 for randomized clinical trials (RCTs) and observational studies that analyzed medication holidays in patients with fragility fracture. Three authors independently extracted data and appraised the risk of bias of the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Effect sizes were pooled in a meta-analysis using random effects models. Primary outcomes were refracture and quality of life; secondary outcomes were mortality and treatment-related adverse events.</p><p><strong>Results: </strong>Six RCTs and nine observational studies met our inclusion criteria, ranging from very low to moderate quality. The adherence to antiosteoporotic drugs was associated with a lower risk of nonvertebral fracture [relative risk (RR) 0.42, 95% confidence interval (CI) 0.20-0.87; three studies] than nonadherence, whereas no difference was detected in the health-related quality of life. A reduction in refracture risk was observed when continuous treatment was compared to discontinuous therapy (RR 0.49, 95% CI 0.25-0.98; three studies). A lower mortality rate was detected for the adherence and persistence measures, while no significant differences were noted in gastrointestinal side effects in individuals undergoing continuous <i>versus</i> discontinuous treatment.</p><p><strong>Conclusion: </strong>Our findings suggest that clinicians should promote adherence and persistence to antiosteoporotic treatment in patients with fragility fractures unless serious adverse effects occur.</p>","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"15 ","pages":"1759720X231177110"},"PeriodicalIF":4.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/05/67/10.1177_1759720X231177110.PMC10286165.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9713406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A prognostic immune nutritional index can predict all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis.","authors":"Sung Soo Ahn,&nbsp;Jung Yoon Pyo,&nbsp;Jason Jungsik Song,&nbsp;Yong-Beom Park,&nbsp;Sang-Won Lee","doi":"10.1177/1759720X231188818","DOIUrl":"https://doi.org/10.1177/1759720X231188818","url":null,"abstract":"<p><strong>Background: </strong>Studies have proposed that nutritional and immune-related markers are relevant with patient outcomes of various medical conditions and could be a useful indicator of patient prognostication.</p><p><strong>Objectives: </strong>This study investigated whether a prognostic immune nutritional index (PINI) at diagnosis could predict adverse clinical outcomes in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).</p><p><strong>Design: </strong>A retrospective, single-centre observational cohort analysis of patients with AAV.</p><p><strong>Methods: </strong>All-cause mortality and end-stage renal disease (ESRD) were investigated outcomes during the observation period. PINI was calculated by serum albumin (g/mL) × 0.9 - monocyte count (/mm³) × 0.0007, and the optimal cut-off of PINI was obtained using a Youden index-based bootstrapping method. Cox hazard analyses were performed to identify independent predictors of patient outcomes.</p><p><strong>Results: </strong>Of the 250 eligible patients, the median age of patients was 60.0 years, and 34.0% were men. During the disease course, 33 (13.2%) died and 42 (16.8%) developed ESRD, respectively. The ideal PINI cut-offs for all-cause mortality and ESRD were set as ⩽2.47 and ⩽3.12 (sensitivity and specificity of 75.1% and 60.6% for mortality and 46.2% and 78.6% for ESRD). AAV patients with PINI ⩽2.47 and those with PINI ⩽3.12 exhibited significantly higher rates for all-cause mortality and ESRD compared to those with PINI >2.47 and >3.12. In the multivariable Cox analysis, PINI ⩽2.47 (hazard ratio [HR]: 3.173, 95% confidence interval [CI]: 1.129, 8.916, <i>p</i> = 0.029) was independently associated with all-cause patient mortality; however, PINI ⩽3.12 was not independently associated with ESRD (HR: 1.097, 95% CI: 0.419, 2.870, <i>p</i> = 0.850).</p><p><strong>Conclusion: </strong>Findings from this study demonstrated PINI could predict all-cause patient mortality in AAV, and a higher clinical attention is warranted in those with PINI ⩽2.47 at initial diagnosis.</p>","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"15 ","pages":"1759720X231188818"},"PeriodicalIF":4.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5c/56/10.1177_1759720X231188818.PMC10387778.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10649798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and characteristics of giant cell arteritis in patients with newly diagnosed polymyalgia rheumatica - a prospective cohort study.","authors":"Lara C Burg,&nbsp;Pantelis Karakostas,&nbsp;Charlotte Behning,&nbsp;Peter Brossart,&nbsp;Tanaz A Kermani,&nbsp;Valentin S Schäfer","doi":"10.1177/1759720X221149963","DOIUrl":"https://doi.org/10.1177/1759720X221149963","url":null,"abstract":"<p><strong>Background: </strong>It is known that giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) often occur together. So far, the prevalence of GCA in newly diagnosed PMR patients has not been evaluated in a prospective ultrasound study.</p><p><strong>Objective: </strong>The aim of this study was to assess the prevalence of GCA using vascular ultrasound in patients with newly diagnosed PMR.</p><p><strong>Design: </strong>A consecutive cohort of newly diagnosed PMR patients was prospectively evaluated for the presence of GCA with the use of systematic musculoskeletal and vascular ultrasound examination.</p><p><strong>Methods: </strong>Overall, 60 patients with newly diagnosed PMR were prospectively enrolled. Symptoms and laboratory findings were collected. All patients underwent ultrasound of shoulder and hip joints, and vascular ultrasound evaluating the facial, temporal, carotid, vertebral and axillary arteries. Patients were diagnosed with GCA if they had ultrasound imaging findings of GCA. Patients with PMR (PMR-group) and patients with PMR and GCA (PMR-GCA-group) were compared, and a C-reactive protein (CRP) cut-off value was evaluated.</p><p><strong>Results: </strong>GCA was diagnosed in 28 of 60 PMR patients (46%). The PMR-group consisted of 20 (62.5%) females with a mean age of 69 (±9.9) years, while the PMR-GCA-group consisted of 11 (39.3%) females with a mean age of 74 (±8.4) years. In 13 of 28 patients (46%) in the PMR-GCA-group, GCA was subclinical and only diagnosed by ultrasound. The PMR-GCA-group showed higher values of joint effusion and significantly higher CRP values. A CRP cut-off value of 26.5 mg/litre (reference range 0-5 mg/litre) yielded a sensitivity of 66% with a specificity of 73% for GCA.</p><p><strong>Conclusion: </strong>GCA was found in 46% of newly diagnosed PMR patients; 22% of the patients with PMR had asymptomatic GCA. Joint effusions were higher in the PMR-GCA-group, with significant results for the hip joint. A CRP cut-off value of ⩾26.5 mg/litre in PMR can help in the identification of subclinical GCA.</p>","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"15 ","pages":"1759720X221149963"},"PeriodicalIF":4.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/94/07/10.1177_1759720X221149963.PMC9909075.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10765732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic lupus erythematosus is associated with increased risk of Parkinson’s disease","authors":"I. Kim, Y. Eun, Jaejoon Lee, K. Han, Da Hye Kim, J. Min, H. Cha, E. Koh, D. Shin, Hyungjin Kim","doi":"10.1177/1759720x231152653","DOIUrl":"https://doi.org/10.1177/1759720x231152653","url":null,"abstract":"A small number of studies have suggested an association between systemic lupus erythematosus (SLE) and Parkinson’s disease (PD). This study aimed to determine the risk of incident PD among Korean patients with SLE. A nationwide retrospective cohort study using the claims database of the National Health Insurance Service of Korea was conducted. Patients above 40 years of age diagnosed with SLE between 2010 and 2015 were included in the study. The primary outcome of the study was incident PD, defined by registration in the rare intractable diseases program for PD and an ICD-10 code of G20. Subjects were followed until PD diagnosis or the end of 2017. We estimated the cumulative incidence of PD among the SLE cohort and compared this to that in a 1:5 age- and sex-matched control group. Totals of 11,615 SLE cases and 58,075 matched controls were identified. The cumulative incidence rate of PD was 0.7 per 1000 person-years in the SLE cohort. The crude hazard ratio (HR) of incident PD was 1.71 (95% CI: 1.25–2.36) among the SLE cohort compared to the control group. The HR was 1.59 (95% CI: 1.15–2.20) after adjustment for age, sex, income, and baseline comorbidities. This study demonstrated that patients with SLE had an increased risk of incident PD compared to non-SLE controls. Further research is required to determine the mechanism underlying this and to elucidate the precise role of systemic inflammation in the development of PD in patients with SLE.","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"1 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43828693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Latest advancements in imaging techniques in OA.","authors":"Daichi Hayashi, Frank W Roemer, Thomas Link, Xiaojuan Li, Feliks Kogan, Neil A Segal, Patrick Omoumi, Ali Guermazi","doi":"10.1177/1759720X221146621","DOIUrl":"10.1177/1759720X221146621","url":null,"abstract":"<p><p>The osteoarthritis (OA) research community has been advocating a shift from radiography-based screening criteria and outcome measures in OA clinical trials to a magnetic resonance imaging (MRI)-based definition of eligibility and endpoint. For conventional morphological MRI, various semiquantitative evaluation tools are available. We have lately witnessed a remarkable technological advance in MRI techniques, including compositional/physiologic imaging and automated quantitative analyses of articular and periarticular structures. More recently, additional technologies were introduced, including positron emission tomography (PET)-MRI, weight-bearing computed tomography (CT), photon-counting spectral CT, shear wave elastography, contrast-enhanced ultrasound, multiscale X-ray phase contrast imaging, and spectroscopic photoacoustic imaging of cartilage. On top of these, we now live in an era in which artificial intelligence is increasingly utilized in medicine. Osteoarthritis imaging is no exception. Successful implementation of artificial intelligence (AI) will hopefully improve the workflow of radiologists, as well as the level of precision and reproducibility in the interpretation of images.</p>","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"14 ","pages":"1759720X221146621"},"PeriodicalIF":3.4,"publicationDate":"2022-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fa/6e/10.1177_1759720X221146621.PMC9806406.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10493814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of adipose-derived mesenchymal stem cells in knee osteoarthritis: a meta-analysis of randomized controlled trials.","authors":"Mohamad R Issa, Ahmad S Naja, Nour Z Bouji, Bernard H Sagherian","doi":"10.1177/1759720X221146005","DOIUrl":"10.1177/1759720X221146005","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Adipose-derived mesenchymal stem cells (ADMSCs) have recently been studied for the treatment of knee osteoarthritis. The goal is pain reduction and improvement of joint function leading to superior health-related quality of life.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;The aim of this study was to provide a comprehensive meta-analysis assessing the evidence on the use of ADMSCs in knee osteoarthritis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;This is a Meta-analysis of randomised controlled trials.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Data sources and methods: &lt;/strong&gt;PubMed/MEDLINE, Embase, and Cochrane Databases were searched for randomized controlled trials using ADMSCs to treat patients with knee osteoarthritis. Only trials comparing ADMSCs to placebo or conservative treatment were included. The outcomes studied were improvement in functional, pain, and quality of life scores along with radiographic findings.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of four trials were included, representing 138 patients with knee osteoarthritis. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) scores favored ADMSCs with a statistically and clinically significant difference over controls at 6- and 12-month follow-ups (&lt;i&gt;p&lt;/i&gt; value &lt; 0.0001). Pain, functional, and quality of life scores also favored ADMSCs at 12-month follow-up (&lt;i&gt;p&lt;/i&gt; value &lt; 0.0001).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;ADMSCs are effective in treating knee osteoarthritis symptoms as observed by functional and pain improvements. Furthermore, ADMSCs injection showed improvement of cartilage integrity, which indicates the potential for regenerating the knee cartilage. Future trials with larger number of patients and longer follow-up periods would help to elaborate further the therapeutic potential of ADMSCs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Plain language summary: &lt;/strong&gt;&lt;b&gt;Adipose-derived mesenchymal stem cells use in knee osteoarthritis&lt;/b&gt; Knee osteoarthritis is an extremely common disease that causes damage of the lining of the knee joint.This will lead to pain and limited range of motion of the knee hence limited functionality.Multiple treatments are used currently for knee osteoarthritis which all aim at slowing down the progression and limiting the need for knee replacement surgery.Adipose-derived mesenchymal stem cells (ADMSCs) are stem cells harvested from the fat around the belly. These stem cells have the potential to be converted into cells of a certain origin (cartilage, muscle, fat).Many studies are being performed to see whether these cells can transform to cartilage and repair the damaged knee joint.In this study, we tried to find how the results of different studies comparing the usual treatments for knee osteoarthritis with that of ADMSCs compared.We were mostly interested in the pain, functional, stiffness, and quality of life scores.We also reviewed the MRI findings to find out whether the lining of the knee joint improved.Four studies were included with 138 patients having","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"14 ","pages":"1759720X221146005"},"PeriodicalIF":3.4,"publicationDate":"2022-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/55/1b/10.1177_1759720X221146005.PMC9806366.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10488063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuro-PIMS-TS: a single case report and review of the literature.","authors":"Antonio Scarcella, Maria Vincenza Mastrolia, Edoardo Marrani, Ilaria Maccora, Ilaria Pagnini, Gabriele Simonini","doi":"10.1177/1759720X221139627","DOIUrl":"10.1177/1759720X221139627","url":null,"abstract":"<p><p>Neurological manifestations related to SARS-CoV-2 infection in adults have been largely reported since the beginning of the pandemic. Subsequent large-scale studies involving children confirmed the occurrence of neurological symptoms associated with SARS-CoV-2 infection also among paediatric patients, especially in the context of paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS). At this regard, we report the challenging case of a 10-month-old baby with PIMS-TS complicated by acute cerebral oedema successfully treated with intravenous immunoglobulins, corticosteroids and anakinra. Our results, combined with the evidence of larger case series suggest that higher inflammatory burden is more frequent in patients with neuro PIMS-TS. As regards neuroimaging, neuroimmune disorders are found to be more common during acute COVID-19, MERS is more frequent during PIMS-TS. Distinct immune mechanisms may underlie these different types of neurological involvement, which are yet to be understood. Further studies are required to better define the physiopathology of neuro PIMS-TS and its possible therapeutical implications.</p>","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"14 ","pages":"1759720X221139627"},"PeriodicalIF":3.4,"publicationDate":"2022-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cc/84/10.1177_1759720X221139627.PMC9749051.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10393104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The current state of the osteoarthritis drug development pipeline: a comprehensive narrative review of the present challenges and future opportunities.","authors":"Heungdeok Kim, Jinwon Seo, Yunsin Lee, Kiwon Park, Thomas A Perry, Nigel K Arden, Ali Mobasheri, Heonsik Choi","doi":"10.1177/1759720X221085952","DOIUrl":"10.1177/1759720X221085952","url":null,"abstract":"<p><p>In this narrative review article, we critically assess the current state of the osteoarthritis (OA) drug development pipeline. We discuss the current state-of-the-art in relation to the development and evaluation of candidate disease-modifying OA drugs (DMOADs) and the limitations associated with the tools and methodologies that are used to assess outcomes in OA clinical trials. We focus on the definition of DMOADs, highlight the need for an updated definition in the form of a consensus statement from all the major stakeholders, including academia, industry, regulatory agencies, and patient organizations, and provide a summary of the results of recent clinical trials of novel DMOAD candidates. We propose that DMOADs should be more appropriately targeted and investigated according to the emerging clinical phenotypes and molecular endotypes of OA. Based on the findings from recent clinical trials, we propose key topics and directions for the development of future DMOADs.</p>","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"14 ","pages":"1759720X221085952"},"PeriodicalIF":3.4,"publicationDate":"2022-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/30/fb/10.1177_1759720X221085952.PMC9732806.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10697847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A glance into the future of gout.","authors":"Francisca Sivera, Mariano Andres, Nicola Dalbeth","doi":"10.1177/1759720X221114098","DOIUrl":"10.1177/1759720X221114098","url":null,"abstract":"<p><p>Gout is characterized by monosodium urate (MSU) crystal deposits in and within joints. These deposits result from persistent hyperuricaemia and most typically lead to recurrent acute inflammatory episodes (gout flares). Even though some aspects of gout are well characterized, uncertainties remain; this upcoming decade should provide further insights into many of these uncertainties. Synovial fluid analysis allows for the identification of MSU crystals and unequivocal diagnosis. Non-invasive methods for diagnosis are being explored, such as Raman spectroscopy and imaging modalities. Both ultrasound and dual-energy computed tomography (DECT) allow the detection of MSU crystals; this not only provides a mean of diagnosis, but also has furthered gout knowledge defining the presence of a preclinical deposition in asymptomatic hyperuricaemia. Scientific consensus establishes the beginning of gout as the beginning of symptoms (usually the first flare), but the concept is currently under review. For effective long-term gout management, the main goal is to promote crystal dissolution treatment by reducing serum urate below 6 mg/dL (or 5 mg/dL if faster crystal dissolution is required). Current urate-lowering therapies' (ULTs) options are limited, with allopurinol and febuxostat being widely available, and probenecid, benzbromarone, and pegloticase available in some regions. New xanthine oxidase inhibitors and, especially, uricosurics inhibiting urate transporter URAT1 are under development; it is probable that the new decade will see a welcomed increase in the gout therapeutic armamentarium. Cardiovascular and renal comorbidities are common in gout patients. Studies determining whether optimal treatment of gout will positively impact these comorbidities are currently lacking, but will hopefully be forthcoming. Overall, the single change that will most impact gout management is greater uptake of international rheumatology society recommendations. Innovative strategies, such as nurse-led interventions based on these recommendations have recently demonstrated treatment success for people with gout.</p>","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"14 ","pages":"1759720X221114098"},"PeriodicalIF":3.4,"publicationDate":"2022-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f5/fd/10.1177_1759720X221114098.PMC9340313.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10259128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}