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1.
Sci Rep ; 12(1): 2408, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35165378

RESUMO

Retirement ages are rising in many countries to offset the challenges of population ageing, but osteoarthritis is an age-associated disease that is becoming more prevalent and may limit capacity to work until older ages. We aimed to assess the impact of osteoarthritis on healthy working life expectancy (HWLE) by comparing HWLE for people with and without osteoarthritis from ages 50 and 65 nationally and in a local area in England. Mortality-linked data for adults aged ≥ 50 years were used from six waves (2002-13) of the English Longitudinal Study of Ageing and from three time points of the North Staffordshire Osteoarthritis Project. HWLE was defined as the average number of years expected to be spent healthy (no limiting long-standing illness) and in paid work (employment or self-employment), and was estimated for people with and without osteoarthritis and by sex and occupation type using interpolated Markov chain multi-state modelling. HWLE from age 50 years was a third lower for people with osteoarthritis compared to people without osteoarthritis both nationally (5.68 95% CI [5.29, 6.07] years compared to 10.00 [9.74, 10.26]) and in North Staffordshire (4.31 [3.68, 4.94] years compared to 6.90 [6.57, 7.24]). HWLE from age 65 years for self-employed people with osteoarthritis exceeded HWLE for people without osteoarthritis in manual or non-manual occupations. Osteoarthritis was associated with a significantly shorter HWLE. People with osteoarthritis are likely to have significantly impaired working ability and capacity to work until older ages, especially in regions with poorer health and work outcomes.


Assuntos
Expectativa de Vida , Osteoartrite/economia , Idoso , Emprego , Inglaterra , Feminino , Nível de Saúde , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Osteoartrite/fisiopatologia , Aposentadoria
3.
Theranostics ; 12(2): 542-557, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34976200

RESUMO

Osteoarthritis (OA) is one of the rapidly growing disability-associated conditions with population aging worldwide. There is a pressing need for precise diagnosis and timely intervention for OA in the early stage. Current clinical imaging modalities, including pain radiography, magnetic resonance imaging, ultrasound, and optical coherent tomography, are limited to provide structural changes when the damage has been established or advanced. It prompts further endeavors in search of novel functional and molecular imaging, which potentially enables early diagnosis and intervention of OA. A hybrid imaging modality based on photothermal effects, photoacoustic imaging, has drawn wide attention in recent years and has seen a variety of biomedical applications, due to its great performance in yielding high-contrast and high-resolution images from structure to function, from tissue down to molecular levels, from animals to human subjects. Photoacoustic imaging has witnessed gratifying potentials and preliminary effects in OA diagnosis. Regarding the treatment of OA, photothermal-triggered therapy has exhibited its attractions for enhanced therapeutic outcomes. In this narrative review, we will discuss photoacoustic imaging for the diagnosis and monitoring of OA at different stages. Structural, functional, and molecular parameter changes associated with OA joints captured by photoacoustics will be summarized, forming the diagnosis perspective of the review. Photothermal therapy applications related to OA will also be discussed herein. Lastly, relevant clinical applications and its potential solutions to extend photoacoustic imaging to deeper OA situations have been proposed. Although some aspects may not be covered, this mini review provides a better understanding of the diagnosis and treatment of OA with exciting innovations based on tissue photothermal effects. It may also inspire more explorations in the field towards earlier and better theranostics of OA.


Assuntos
Osteoartrite/diagnóstico , Osteoartrite/terapia , Animais , Liberação Controlada de Fármacos , Elasticidade , Humanos , Peróxido de Hidrogênio/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/fisiopatologia , Técnicas Fotoacústicas
4.
Theranostics ; 12(2): 891-909, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34976219

RESUMO

Osteoarthritis (OA) is a prevalent debilitating age-related joint degenerative disease. It is a leading cause of pain and functional disability in older adults. Unfortunately, there is no cure for OA once the damage is established. Therefore, it promotes an urgent need for early detection and intervention of OA. Theranostics, combining therapy and diagnosis, emerges as a promising approach for OA management. However, OA theranostics is still in its infancy. Three fundamental needs have to be firstly fulfilled: i) a reliable OA model for disease pathogenesis investigation and drug screening, ii) an effective and precise diagnostic platform, and iii) an advanced fabrication approach for drug delivery and therapy. Meanwhile, microfluidics emerges as a versatile technology to address each of the needs and eventually boost the development of OA theranostics. Therefore, this review focuses on the applications of microfluidics, from benchtop to bedside, for OA modelling and drug screening, early diagnosis, and clinical therapy. We first introduce the basic pathophysiology of OA and point out the major unfilled research gaps in current OA management including lack of disease modelling and drug screening platforms, early diagnostic modalities and disease-modifying drugs and delivery approaches. Accordingly, we then summarize the state-of-the-art microfluidics technology for OA management from in vitro modelling and diagnosis to therapy. Given the existing promising results, we further discuss the future development of microfluidic platforms towards clinical translation at the crossroad of engineering and biomedicine.


Assuntos
Microfluídica , Osteoartrite , Animais , Técnicas Biossensoriais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Humanos , Microfluídica/tendências , Osteoartrite/diagnóstico , Osteoartrite/tratamento farmacológico , Osteoartrite/fisiopatologia , Osteoartrite/terapia , Sistemas Automatizados de Assistência Junto ao Leito , Medicina de Precisão
5.
Behav Pharmacol ; 33(1): 23-31, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35007233

RESUMO

The monoiodoacetate-induced rat model of osteoarthritis knee pain is widely used. However, there are between-study differences in the pain behavioural endpoints assessed and in the dose of intraarticular monoiodoacetate administered. This study evaluated the robustness of gait analysis as a pain behavioural endpoint in the chronic phase of this model, in comparison with mechanical hyperalgesia in the injected (ipsilateral) joint and development of mechanical allodynia in the ipsilateral hind paws. Groups of Sprague-Dawley rats received a single intraarticular injection of monoiodoacetate at 0.5, 1, 2 or 3 mg or vehicle (saline) into the left (ipsilateral) knee joint. An additional group of rats were not injected (naïve group). The pain behavioural methods used were gait analysis, measurement of pressure algometry thresholds in the ipsilateral knee joints, and assessment of mechanical allodynia in the ipsilateral hind paws using von Frey filaments. These pain behavioural endpoints were assessed premonoiodoacetate injection and for up to 42-days postmonoiodoacetate injection in a blinded manner. Body weights were also assessed as a measure of general health. Good general health was maintained as all rats gained weight at a similar rate for the 42-day study period. In the chronic phase of the model (days 9-42), intraarticular monoiodoacetate at 3 mg evoked robust alterations in multiple gait parameters as well as persistent mechanical allodynia in the ipsilateral hind paws. For the chronic phase of the monoiodoacetate-induced rat model of osteoarthritis knee pain, gait analysis, such as mechanical allodynia in the ipsilateral hind paws, is a robust pain behavioural measure.


Assuntos
Artralgia , Sintomas Comportamentais , Análise da Marcha/métodos , Hiperalgesia , Osteoartrite , Dor , Animais , Artralgia/induzido quimicamente , Artralgia/psicologia , Técnicas de Observação do Comportamento/métodos , Comportamento Animal , Sintomas Comportamentais/diagnóstico , Sintomas Comportamentais/fisiopatologia , Modelos Animais de Doenças , Inibidores Enzimáticos/administração & dosagem , Hiperalgesia/diagnóstico , Hiperalgesia/fisiopatologia , Hiperalgesia/psicologia , Ácido Iodoacético/administração & dosagem , Osteoartrite/fisiopatologia , Osteoartrite/psicologia , Dor/fisiopatologia , Dor/psicologia , Ratos , Ratos Sprague-Dawley
6.
Int J Rheum Dis ; 25(1): 38-46, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34821056

RESUMO

AIM: To investigate the associations of ultrasound and radiographic features of thumb-base osteoarthritis (OA) with thumb-base pain and hand function at baseline and 12 weeks. METHOD: Data from a randomized controlled trial conducted in participants with symptomatic radiographic thumb-base OA were analyzed. Participants who finished follow up were included in this secondary analysis. Pain and hand function were assessed using self-reported measures. All participants underwent ultrasound examinations for synovitis, power Doppler signal (PDS), and osteophytes, and underwent radiography for osteophytes, joint space narrowing (JSN), and subchondral bone sclerosis at baseline. Hand pain and function were reassessed after the 12-week follow up. The associations of ultrasound and radiographic findings with clinical features were further evaluated, using linear regression analyses, after adjustment for relevant confounding factors. RESULTS: A total of 166 participants (average age 66.2 years; 76.5% female) were included. At baseline, radiographic JSN and subchondral bone sclerosis were associated with hand function. There was a significant association between ultrasound-detected PDS and patient's global assessment (PGA) at baseline. Baseline radiographic JSN was significantly associated with the changes in stiffness and PGA from baseline to 12 weeks. There was no association between ultrasound features and changes in the clinical outcomes over 12 weeks. CONCLUSION: This study indicates that radiographic features significantly correlate with hand function, and ultrasound PDS is closely related to the PGA at baseline in thumb-base OA. Radiographic JSN may be a predictor for stiffness and PGA in thumb-base OA.


Assuntos
Articulações Carpometacarpais/fisiopatologia , Osteoartrite/fisiopatologia , Idoso , Articulações Carpometacarpais/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Osteoartrite/diagnóstico por imagem , Estudos Prospectivos , Radiografia , Polegar/diagnóstico por imagem , Ultrassonografia
7.
J Bone Miner Metab ; 40(2): 196-207, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34751824

RESUMO

INTRODUCTION: A disintegrin and metalloproteinase 17 (Adam17), also known as TNFα-converting enzyme (Tace), is a membrane-anchored protein involved in shedding of TNF, IL-6 receptor, ligands of epidermal growth factor receptor (EGFR), and Notch receptor. This study aimed to examine the role of Adam17 in adult articular cartilage and osteoarthritis (OA) pathophysiology. MATERIALS AND METHODS: Adam17 expression was examined in mouse knee joints during OA development. We analyzed OA development in tamoxifen-inducible chondrocyte-specific Adam17 knockout mice of a resection of the medial meniscus and medial collateral ligament (medial) model, destabilization of the medial meniscus (DMM) model, and aging model. We analyzed downstream pathways by in vitro experiments, and further performed intra-articular administration of an Adam17 inhibitor TAPI-0 for surgically induced mouse OA. RESULTS: Adam17 expression in mouse articular cartilage was increased by OA progression. In all models, Adam17 knockout mice showed ameliorated progression of articular cartilage degradation. Adam17 knockout decreased matrix metallopeptidase 13 (Mmp13) expression in both in vivo and in vitro experiments, whereas Adam17 activation by phorbol-12-myristate-13-acetate (PMA) increased Mmp13 and decreased aggrecan in mouse primary chondrocytes. Adam17 activation enhanced release of soluble TNF and transforming growth factor alpha, a representative EGF ligand, from mouse primary chondrocytes, while it did not change release of soluble IL-6 receptor or nuclear translocation of Notch1 intercellular domain. Intra-articular administration of the Adam17 inhibitor ameliorated OA progression. CONCLUSIONS: This study demonstrates regulation of OA development by Adam17, involvement of EGFR and TNF pathways, and the possibility of Adam17 as a therapeutic target for OA.


Assuntos
Proteína ADAM17/metabolismo , Cartilagem Articular , Osteoartrite , Animais , Cartilagem Articular/metabolismo , Cartilagem Articular/fisiopatologia , Condrócitos/metabolismo , Modelos Animais de Doenças , Articulação do Joelho/fisiopatologia , Metaloproteinase 13 da Matriz/metabolismo , Camundongos , Camundongos Knockout , Osteoartrite/metabolismo , Osteoartrite/fisiopatologia
9.
Neuropharmacology ; 204: 108908, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34856202

RESUMO

Osteoarthritis (OA) is a chronic joint disease in which cartilage degeneration leads to chronic pain. The endocannabinoid system has attracted attention as an emerging drug target for OA. However, the therapeutic potential of cannabinoids is limited by psychoactive side-effects related to CB1 activation and tolerance development for analgesic effects. ß-Caryophyllene (BCP) is a low-efficacy natural agonist of CB2 and a common constituent of human diet with well-established anti-inflammatory properties. The results presented herein show the anti-nociceptive and chondroprotective potential of BCP in an animal model of OA induced by intra-articular injection of monoiodoacetate (MIA). Behavioural assessment included pressure application measurement and kinetic weight bearing tests. Histological assessment of cartilage degeneration was quantified using OARSI scoring. Experiments established the dose-response effects of BCP and pharmacological mechanisms of the antinociceptive action dependent on CB2 and opioid receptors. Chronic BCP treatment was able to hamper cartilage degeneration without producing tolerance for the analgesic effects. The data presented herein show that BCP is able to produce both acute and prolonged antinociceptive and chondroprotective effects. Together with the safety profile and legal status of BCP, these results indicate a novel and promising disease-modifying strategy for treating OA.


Assuntos
Analgésicos , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos , Osteoartrite/tratamento farmacológico , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Policíclicos/uso terapêutico , Animais , Cartilagem/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Tolerância a Medicamentos , Masculino , Osteoartrite/patologia , Osteoartrite/fisiopatologia , Ratos Wistar , Receptor CB2 de Canabinoide/agonistas , Suporte de Carga
10.
Clin Orthop Relat Res ; 480(2): 354-363, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34435980

RESUMO

BACKGROUND: Despite the routine use of plain radiographs to stratify the severity of glenohumeral osteoarthritis, little is known about the relationship between radiographic measures and patient-perceived pain and function. QUESTIONS/PURPOSES: (1) What radiographic findings are associated with worse pain and function in patients with glenohumeral osteoarthritis? (2) What demographic factors are associated with worse pain and function in patients with glenohumeral osteoarthritis? METHODS: This retrospective study included patients presenting for an initial office visit for primary glenohumeral osteoarthritis. Patients with other concurrent shoulder pathologic findings, prior surgery, lack of pain and functional scores, recent injection, or inadequate radiographs were excluded. Between January 2017 and January 2019, 3133 patients were eligible based on these inclusion criteria; 59% (1860) had outcome assessments and 48% (893) of those had radiographs. An additional 42% (378) of those with radiographs were excluded because of other shoulder findings, recent injection, prior surgery, or inadequate radiographs, leaving 16% (515 of 3133) who were fully analyzed in this study. A radiographic review included the joint space width, posterior humeral head subluxation, inferior humeral head osteophyte size, cystic change, and head asphericity. Additionally, radiographic arthritis was classified according to the Walch, Samilson-Prieto, and Kellgren-Lawrence classifications by two separate reviewers. Radiographic and demographic criteria as well as the presence of psychologic or mental illness were correlated with VAS Pain (range 1-10; minimal clinically important difference [MCID] 1.6), American Shoulder and Elbow Surgeons (ASES; range 0-100; MCID 13.6), Single Assessment Numeric Evaluation (SANE; range 0-100; MCID 14), and Simple Shoulder Test (SST; range 0-12; MCID 1.5) scores using univariate and multivariable regression analyses. RESULTS: After accounting for age, gender, and psychologic illness in the multivariable analysis, we found that patients with Samilson-Prieto Grade 4 arthrosis had lower VAS Pain scores (ß = -1.9; p = 0.02) than those with Grade 0 or 1 did; however, no clinically important associations were found between Samilson-Prieto Grade 4 and ASES (ß = 7; p = 0.25), SANE (ß = 4; p = 0.63), or SST (ß = 0.5; p = 0.62) scores. No clinically important associations were found between Kellgren-Lawrence Grade 3 and VAS Pain (ß = 1.4; p = 0.10), ASES (ß = -8; p = 0.22), SANE (ß = -13; p = 0.11), or SST scores (ß = 0.4; p = 0.66). Radiographic joint space and posterior subluxation also did not have any clinically important associations with VAS Pain or functional scores. In assessing Walch glenoid type, there was no clinically important association between glenoid type and VAS Pain (F = 3.1; p < 0.01), ASES (F = 1.9; p = 0.15), SANE (F = 0.45; p = 0.66), or SST scores (F = 0.76; p = 0.71). Men had higher SST scores than women did (ß = 2.0; p < 0.01), but there were no clinically important differences in VAS Pain (ß = -0.4; p = 0.04), ASES (ß = 6; p < 0.01), or SANE (ß = 4; p = 0.07) scores. No clinically important association was found between age or the presence of any psychologic illness and VAS Pain or functional scores. CONCLUSION: In patients with glenohumeral arthritis, no consistent clinically important differences in pain or function were discovered with respect to radiographic or demographic factors. Surgeons should understand that the pain levels of patients with glenohumeral arthritis may not parallel radiographic severity. Future studies can build on these findings by examining other non-radiographic or demographic factors that affect pain in patients with shoulder arthritis, such as psychological factors. LEVEL OF EVIDENCE: Level III, prognostic study.


Assuntos
Dor Musculoesquelética/diagnóstico por imagem , Dor Musculoesquelética/fisiopatologia , Osteoartrite/diagnóstico por imagem , Osteoartrite/fisiopatologia , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Radiografia , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários
11.
AJR Am J Roentgenol ; 218(3): 405-417, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34286595

RESUMO

Synovitis, inflammation of the synovial membrane, is a common manifestation of osteoarthritis (OA) and is recognized to play a role in the complex pathophysiology of OA. Increased recognition of the importance of synovitis in the OA disease process and its potential as a target for treatment has increased the need for noninvasive detection and characterization of synovitis using medical imaging. Numerous imaging methods can assess synovitis involvement in OA with varying sensitivity, specificity, and complexity. This article reviews the role of contrast-enhanced MRI, conventional MRI, novel unenhanced MRI, gray-scale ultrasound (US), and power Doppler US in the assessment of synovitis in patients with OA. The role of imaging in disease evaluation and the challenges of conventional imaging methods are discussed. We also provide an overview of the potential utility of emerging techniques for imaging of early inflammation and molecular inflammatory markers of synovitis, including quantitative MRI, superb microvascular imaging, and PET. The development of therapeutic treatments targeting inflammatory features, particularly in early OA, would greatly increase the importance of these imaging methods for clinical decision-making and evaluation of therapeutic efficacy.


Assuntos
Diagnóstico por Imagem/métodos , Inflamação/diagnóstico por imagem , Inflamação/etiologia , Osteoartrite/complicações , Osteoartrite/diagnóstico por imagem , Membrana Sinovial/diagnóstico por imagem , Humanos , Inflamação/fisiopatologia , Osteoartrite/fisiopatologia , Membrana Sinovial/fisiopatologia
12.
PLoS One ; 16(12): e0261353, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34914764

RESUMO

BACKGROUND: Along with mechanical and genetic factors, emerging evidence suggests that the presence of low-grade inflammation has a role in the pathogenesis of osteoarthritis (OA) and seems to be related to the microbiome composition of the gut. PURPOSE: To provide evidence whether there is clinical or preclinical evidence of gut-joint axis in the pathogenesis and symptoms of OA. METHODS: An extensive review of the current literature was performed using three different databases. Human, as well as animal studies, were included. The risk of bias was identified using ROBINS and SYRCLE tools, while the quality of evidence was assessed using GRADE and CAMADARES criteria. RESULTS: A total of nineteen articles were included. Multiple animal studies demonstrated that both obesity, and high-fat and high-sugar diets resulted in a gut dysbiosis status characterized by increased Firmicutes/Bacteroidetes (F/B) phyla ratio and increased permeability. These changes were associated with increased lipopolysaccharide serum levels, which consequently resulted in synovitis and OA severity. The administration of pre-and probiotics partially reversed this bacterial composition. In addition, in human studies, a decreased amount of gut Bacteroidetes, subsequent increased F/B ratio, have also been observed in OA patients. CONCLUSIONS: Our review confirms preliminary yet sound evidence supporting a gut-joint axis in OA in primarily preclinical models, by showing an association between diet, gut dysbiosis and OA radiological severity and self-reported symptoms. Clinical studies are needed to confirm these findings, and to investigate whether interventions targeting the composition of the microbiome will have a beneficial clinical effect.


Assuntos
Microbioma Gastrointestinal/fisiologia , Osteoartrite/microbiologia , Osteoartrite/fisiopatologia , Disbiose/microbiologia , Microbioma Gastrointestinal/genética , Humanos , Inflamação/patologia , Articulações/patologia , Osteoartrite/complicações , Probióticos/uso terapêutico
13.
Int J Mol Sci ; 22(24)2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34948080

RESUMO

MicroRNAs (miRNAs) can be transported in extracellular vesicles (EVs) and are qualified as possible messengers for cell-cell communication. In the context of osteoarthritis (OA), miR-221-3p has been shown to have a mechanosensitive and a paracrine function inside cartilage. However, the question remains if EVs with miR-221-3p can act as molecular mechanotransducers between cells of different tissues. Here, we studied the effect of EV-mediated transport in the communication between chondrocytes and osteoblasts in vitro in a rat model. In silico analysis (Targetscan, miRWalk, miRDB) revealed putative targets of miRNA-221-3p (CDKN1B/p27, TIMP-3, Tcf7l2/TCF4, ARNT). Indeed, transfection of miRNA-221-3p in chondrocytes and osteoblasts resulted in regulation of these targets. Coculture experiments of transfected chondrocytes with untransfected osteoblasts not only showed regulation of these target genes in osteoblasts but also inhibition of their bone formation capacity. Direct treatment with chondrocyte-derived EVs validated that chondrocyte-produced extracellular miR-221-3p was responsible for this effect. Altogether, our study provides a novel perspective on a possible communication pathway of a mechanically induced epigenetic signal through EVs. This may be important for processes at the interface of bone and cartilage, such as OA development, physiologic joint homeostasis, growth or fracture healing, as well as for other tissue interfaces with differing biomechanical properties.


Assuntos
Condrócitos/metabolismo , Mecanotransdução Celular , MicroRNAs/metabolismo , Osteoartrite/metabolismo , Osteoblastos/fisiologia , Animais , Comunicação Celular , Células Cultivadas , Condrócitos/fisiologia , Técnicas de Cocultura , Simulação por Computador , Modelos Animais de Doenças , Epigênese Genética , Vesículas Extracelulares , MicroRNAs/fisiologia , Osteoartrite/genética , Osteoartrite/fisiopatologia , Ratos , Ratos Wistar
14.
J Manag Care Spec Pharm ; 27(12): 1652-1660, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34818088

RESUMO

BACKGROUND: Osteoarthritis (OA) affects millions of adults in the United States and can result in substantial pain, functional impairment, and significant clinical and economic burden. To manage chronic pain associated with OA, treatment guidelines recommend a variety of pharmacologic treatments, including traditional oral nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors (COX-2s), and opioids. While these drug treatments can be effective at pain management, they are also associated with significant clinical and economic burden. New treatments for chronic pain among patients with OA of the hip and/or knee have the potential to reduce the occurrence of such negative clinical outcomes, including cardiovascular events, renal events, and opioid use disorder (OUD), thereby reducing health care resource use (HRU) and medical costs. OBJECTIVE: To develop a harm reduction model (HRM) to assess potential reductions of negative clinical outcomes, HRU, and medical costs associated with the use of new treatments in place of oral NSAIDs, tramadol, and non-tramadol opioids among patients with OA of the hip and/or knee in the United States. METHODS: The HRM model integrated findings from the literature and inputs from a variety of sources, along with assumptions regarding potential ability of new treatments to replace existing treatments and market penetration into a unified framework to estimate outcomes and costs. The model outputs included estimated per-patient and population-level reductions in negative clinical outcomes associated with prescribing new treatments in place of oral NSAIDs or opioids along with number needed to treat (NNT) associated with new treatments. The model assumed that new treatments will primarily be used in place of non-tramadol opioids, but more modest adoption in place of oral NSAIDs and tramadol. RESULTS: Among patients with OA of the hip and/or knee who were prescribed oral NSAIDs, tramadol, or non-tramadol opioids for chronic use (≥ 90 days), the HRM estimated total cost savings of $3.8 billion, $5.1 billion, and $29.9 billion, respectively, from prescribing new treatments for OA pain over a 36-month period. The reduced economic burden was driven by significant reductions in the incidence of negative clinical outcomes. Estimates of the NNT to avoid a negative clinical event related to NSAID and opioid treatment initiation were low for most outcomes. Estimates of NNT associated with NSAID use ranged from 4 to 17 patients, depending on outcome, and estimates of NNT associated with opioid use was 35 non-tramadol and 134 tramadol patients for OUD and ranged from 6 to 21 patients for the other clinical outcomes, depending on treatment and outcome. CONCLUSIONS: Results from the HRM suggest that prescribing new treatments in place of oral NSAIDs and/or opioids for OA pain results in a potentially substantial reduction in patients experiencing negative clinical outcomes and reductions in all-cause HRU and costs. DISCLOSURES: This study was sponsored by Pfizer and Eli Lilly and Company. Silverman was a paid consultant to Pfizer and Eli Lilly and Company in connection with this study. Beck and Schepman are employees of Pfizer with stock and/or stock options. Robinson is an employee and minor stockholder of Eli Lilly and Company. Rice, White, and Fernan are employees of the Analysis Group, who were paid consultants to Pfizer and Eli Lilly and Company for this study and development of the manuscript.


Assuntos
Redução do Dano , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite/tratamento farmacológico , Osteoartrite/fisiopatologia , Avaliação de Resultados em Cuidados de Saúde , Manejo da Dor , Padrão de Cuidado , Anti-Inflamatórios não Esteroides/uso terapêutico , Dor Crônica/tratamento farmacológico , Humanos , Estados Unidos
15.
Inflammopharmacology ; 29(6): 1653-1667, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34755232

RESUMO

The accelerated prevalence of osteoarthritis (OA) disease worldwide and the lack of convenient management led to the frequent search for unprecedented and specific treatment approaches. OA patients usually suffer from many annoying complications that negatively influence their quality of life, especially in the elderly. Articular erosions may lead eventually to the loss of joint function as a whole which occurs over time according to the risk factors presented in each case and the grade of the disease. Conventional therapies are advancing, showing most appropriate results but still greatly associated with many adverse effects and have restricted curative actions as well. Hence, novel management tools are usually required. In this review, we summarized the recent approaches in OA treatment and the role of natural products, dietary supplements and nanogold application in OA treatment to provide new research tracks for more therapeutic opportunities to those who are in care in this field.


Assuntos
Osteoartrite/terapia , Qualidade de Vida , Idoso , Animais , Produtos Biológicos/uso terapêutico , Suplementos Nutricionais , Ouro , Humanos , Nanopartículas Metálicas , Osteoartrite/complicações , Osteoartrite/fisiopatologia , Fatores de Risco
16.
PLoS One ; 16(11): e0257310, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34735461

RESUMO

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the intestinal tract and is associated with decreased bone mineral density. IBD patients are at higher risk of osteopenia, osteoporosis and fracture compared to non-IBD patients. The impact of IBD on the performance of orthopedic implants has not been well studied. We hypothesized that a history of IBD at the time of primary total hip arthroplasty (THA) would increase the risk of subsequent failure as assessed by revision surgery. A retrospective implant survival analysis was completed using the Swedish Hip Arthroplasty Registry and the Sweden National Patient Register. A total of 150,073 patients undergoing THA for osteoarthritis within an 18-year period were included in the study. THA patients with (n = 2,604) and without (n = 147,469) a history of IBD at the time of THA were compared with primary revision as the main endpoint and adjusted using sex, age category and comorbidity (Elixhauser scores) as covariates. We found that patients with a history of IBD had a relatively higher risk of revision surgery for septic causes while the non-IBD patients had a relatively higher risk of revision for aseptic causes (p = 0.004). Our findings suggest there may be an association between gut health and THA performance.


Assuntos
Densidade Óssea , Doenças Inflamatórias Intestinais/cirurgia , Osteoartrite/cirurgia , Reoperação , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/fisiopatologia , Doenças Ósseas Metabólicas/cirurgia , Feminino , Prótese de Quadril/efeitos adversos , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoartrite/etiologia , Osteoartrite/fisiopatologia , Osteoporose/etiologia , Osteoporose/fisiopatologia , Osteoporose/cirurgia , Falha de Prótese/efeitos adversos , Sistema de Registros , Fatores de Risco , Suécia
17.
Int J Mol Sci ; 22(21)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34769215

RESUMO

Oxytocin (OT) is involved in breastfeeding and childbirth and appears to play a role in regulating the bone matrix. OT is synthesized in the supraoptic and paraventricular nuclei of the hypothalamus and is released in response to numerous stimuli. It also appears to be produced by osteoblasts in the bone marrow, acting as a paracrine-autocrine regulator of bone formation. Osteoarthritis (OA) is a disease of the whole joint. Different tissues involved in OA express OT receptors (OTRs), such as chondrocytes and osteoblasts. This hormone, which levels are reduced in patients with OA, appears to have a stimulatory effect on chondrogenesis. OT involvement in bone biology could occur at both the osteoblast and chondrocyte levels. The relationships between metabolic syndrome, body weight, and OA are well documented, and the possible effects of OT on different parameters of metabolic syndrome, such as diabetes and body weight, are important. In addition, the effects of OT on adipokines and inflammation are also discussed, especially since recent data have shown that low-grade inflammation is also associated with OA. Furthermore, OT also appears to mediate endogenous analgesia in animal and human studies. These observations provide support for the possible interest of OT in OA and its potential therapeutic treatment.


Assuntos
Osteoartrite/metabolismo , Ocitocina/metabolismo , Adipocinas/metabolismo , Animais , Condrócitos/metabolismo , Condrócitos/patologia , Condrogênese , Humanos , Osteoartrite/patologia , Osteoartrite/fisiopatologia , Osteoblastos/metabolismo , Osteoblastos/patologia , Receptores de Ocitocina/metabolismo
18.
Plast Reconstr Surg ; 148(5): 811e-824e, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34705791

RESUMO

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Comprehend anatomy and biomechanics of the normal and arthritic trapeziometacarpal joint. 2. Evaluate best evidence for diagnosis and for operative and nonoperative treatment of thumb osteoarthritis. 3. Understand treatment pitfalls of basilar joint arthritis and complication avoidance. SUMMARY: Articular and ligamentous anatomy of the trapeziometacarpal joint enables complex motions. Disability from arthritis, common at the trapeziometacarpal joint, is debilitating. Furthering the understanding of how trapeziometacarpal arthritis develops can improve treatment. The authors provide current best evidence for diagnosis and treatment of basilar joint arthritis. Pitfalls in treatment are discussed.


Assuntos
Articulações Carpometacarpais/cirurgia , Procedimentos Ortopédicos/métodos , Osteoartrite/cirurgia , Complicações Pós-Operatórias/epidemiologia , Polegar/cirurgia , Fatores Etários , Articulações Carpometacarpais/diagnóstico por imagem , Articulações Carpometacarpais/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos/efeitos adversos , Osteoartrite/diagnóstico , Osteoartrite/fisiopatologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/cirurgia , Amplitude de Movimento Articular , Reoperação/estatística & dados numéricos , Fatores de Risco , Índice de Gravidade de Doença , Polegar/diagnóstico por imagem , Polegar/fisiopatologia , Resultado do Tratamento
19.
Molecules ; 26(20)2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34684706

RESUMO

The remarkable lubrication properties of normal articular cartilage play an essential role in daily life, providing almost frictionless movements of joints. Alterations of cartilage surface or degradation of biomacromolecules within synovial fluid increase the wear and tear of the cartilage and hence determining the onset of the most common joint disease, osteoarthritis (OA). The irreversible and progressive degradation of articular cartilage is the hallmark of OA. Considering the absence of effective options to treat OA, the mechanosensitivity of chondrocytes has captured attention. As the only embedded cells in cartilage, the metabolism of chondrocytes is essential in maintaining homeostasis of cartilage, which triggers motivations to understand what is behind the low friction of cartilage and develop biolubrication-based strategies to postpone or even possibly heal OA. This review firstly focuses on the mechanism of cartilage lubrication, particularly on boundary lubrication. Then the mechanotransduction (especially shear stress) of chondrocytes is discussed. The following summarizes the recent development of cartilage-inspired biolubricants to highlight the correlation between cartilage lubrication and OA. One might expect that the restoration of cartilage lubrication at the early stage of OA could potentially promote the regeneration of cartilage and reverse its pathology to cure OA.


Assuntos
Cartilagem/fisiologia , Osteoartrite/fisiopatologia , Líquido Sinovial/metabolismo , Animais , Fenômenos Biofísicos/fisiologia , Cartilagem/metabolismo , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Fricção , Humanos , Ácido Hialurônico/metabolismo , Mecanotransdução Celular , Estresse Mecânico
20.
Arch Pediatr ; 28(7): 606-611, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34625379

RESUMO

X-linked hypophosphatemia (XLH) is a rare genetic phosphate disorder caused mainly by PHEX mutations. Unlike for children, knowledge of the disease's manifestations in adults is limited. Musculoskeletal symptoms are the main feature of the disease in young adults associated with a heavy burden on patients' life. They include fractures and pseudofractures, pain, joint stiffness, osteoarthritis, enthesopathies, and muscle weakness, eventually leading to impaired quality of life. Conventional treatment with phosphate supplements and vitamin D analogs is indicated in symptomatic patients. Appropriate rehabilitation is also a key to the management of the disease to improve physical function and decrease pain, stiffness, and fatigue. Regarding the incidence and consequences of musculoskeletal features in XLH, all patients should be assessed by a bone disease specialist and, if necessary, managed by a multidisciplinary team.


Assuntos
Raquitismo Hipofosfatêmico Familiar/complicações , Raquitismo Hipofosfatêmico Familiar/terapia , Entesopatia/etiologia , Entesopatia/fisiopatologia , Raquitismo Hipofosfatêmico Familiar/fisiopatologia , Humanos , Mutação/genética , Osteoartrite/etiologia , Osteoartrite/fisiopatologia , Endopeptidase Neutra Reguladora de Fosfato PHEX/genética
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