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1.
Ann Rheum Dis ; 72(10): 1594-604, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23887285

RESUMO

Knee osteoarthritis is associated with structural changes in the joint. Despite its many drawbacks, radiography is the current standard for evaluating joint structure in trials of potential disease-modifying osteoarthritis drugs. MRI is a non-invasive alternative that provides comprehensive imaging of the whole joint. Frequently used MRI measurements in knee osteoarthritis are cartilage volume and thickness; others include synovitis, synovial fluid effusions, bone marrow lesions (BML) and meniscal damage. Joint replacement is considered a clinically relevant outcome in knee osteoarthritis; however, its utility in clinical trials is limited. An alternative is virtual knee replacement on the basis of symptoms and structural damage. MRI may prove to be a good alternative to radiography in definitions of knee replacement. One of the MRI parameters that predicts knee replacement is medial compartment cartilage volume/thickness, which correlates with radiographic joint space width, is sensitive to change, and predicts outcomes in a continuous manner. Other MRI parameters include BML and meniscal lesions. MRI appears to be a viable alternative to radiography for the evaluation of structural changes in knee osteoarthritis and prediction of joint replacement.


Assuntos
Artroplastia do Joelho , Imageamento por Ressonância Magnética/métodos , Osteoartrite do Joelho/patologia , Artroplastia do Joelho/estatística & dados numéricos , Medula Óssea/patologia , Cartilagem Articular/patologia , Progressão da Doença , Humanos , Meniscos Tibiais/patologia , Osteoartrite do Joelho/cirurgia , Sinovite/patologia
2.
Ann Rheum Dis ; 70(11): 1949-56, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21821865

RESUMO

OBJECTIVE: To assess the efficacy and safety of abatacept plus methotrexate versus methotrexate alone in early erosive rheumatoid arthritis (RA). METHODS: The AGREE was a 2-year phase IIIb multinational study in early (≤ 2 years) RA. During the double-blind period (year 1), patients were randomly assigned 1:1 to receive abatacept+methotrexate or methotrexate alone; all patients received open-label abatacept+methotrexate during year 2. Clinical outcomes assessed included 28-joint disease activity score (DAS28) defined remission, low disease activity score (LDAS), American College of Rheumatology (ACR) responses and physical function. Radiographic outcomes were assessed using the Genant-modified Sharp total score (TS). Safety was monitored throughout. RESULTS: Of the 459 patients completing year 1, 433 patients (94.3%) completed year 2. DAS28-defined remission, LDAS, ACR and physical function were sustained through year 2 in the original abatacept+methotrexate group, with 55.2% in remission at 2 years. Upon introduction of abatacept in the methotrexate-alone group, additional patients achieved DAS28-defined remission (44.5% vs 26.9%), LDAS (60.4% vs 43.2%) and improved ACR 70 (49.8% vs 31.7%) for year 2 versus year 1. Less radiographic progression was observed at 2 years in the original abatacept+methotrexate group than the methotrexate-alone group (change in TS 0.84 vs 1.75, p<0.001). No new safety issues were seen. Similar rates of serious adverse events, serious infections and autoimmune events were observed in years 1 and 2. CONCLUSIONS: The AGREE trial was the first to examine the impact of T-cell co-stimulation modulation with abatacept in patients with early erosive RA. Early treatment with abatacept+methotrexate resulted in greater sustainable clinical, functional and radiographic benefits than methotrexate alone, with acceptable safety and tolerability. TRIAL REGISTRATION: NCT00122382.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Imunoconjugados/uso terapêutico , Metotrexato/uso terapêutico , Abatacepte , Adulto , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/fisiopatologia , Progressão da Doença , Quimioterapia Combinada , Métodos Epidemiológicos , Feminino , Humanos , Imunoconjugados/efeitos adversos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Radiografia , Indução de Remissão , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
3.
Arthritis Care Res (Hoboken) ; 62(4): 569-74, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20391513

RESUMO

OBJECTIVE: Periarticular osteoporosis is one of the earliest radiographic signs of bone damage in rheumatoid arthritis (RA). Denosumab, an investigational fully human monoclonal antibody that binds to RANKL, inhibits bone erosion and systemic bone loss in clinical studies of patients with RA. In this hand bone mineral density (BMD) substudy, we investigated the effects of denosumab on hand BMD and its correlation with hand erosion scores. METHODS: Patients receiving methotrexate for erosive RA were randomized in a 1:1:1 ratio to receive subcutaneous placebo, denosumab 60 mg, or denosumab 180 mg at 0 and 6 months. Measurements included BMD (by dual x-ray absorptiometry [DXA]) of both hands (0, 1, 6, and 12 months), magnetic resonance images of the hands/wrists (0 and 6 months), and radiographs of the hands/wrists and feet (0, 6, and 12 months). RESULTS: There were 56 patients (13 placebo, 21 denosumab 60 mg, and 22 denosumab 180 mg). Mean changes in hand BMD at 6 and 12 months were: +0.8% and +1.0%, respectively, for denosumab 60 mg; +2.0% and +2.5%, respectively, for denosumab 180 mg; and -1.2% and -2.0%, respectively, for placebo. Erosion scores remained near baseline in the denosumab groups and increased from baseline in the placebo group. A negative correlation was observed between hand BMD and erosion scores. CONCLUSION: In patients with RA, denosumab provided protection against erosion, and not only prevented bone loss but increased hand BMD as measured by DXA.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/prevenção & controle , Ligante RANK/administração & dosagem , Adulto , Idoso , Anticorpos Monoclonais Humanizados , Artrite Reumatoide/complicações , Reabsorção Óssea/etiologia , Denosumab , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipodermóclise , Masculino , Pessoa de Meia-Idade
4.
Ann Rheum Dis ; 68(12): 1870-7, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19124524

RESUMO

OBJECTIVES: To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors. METHODS: In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (approximately 10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout. RESULTS: At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p = 0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone. CONCLUSIONS: In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Imunoconjugados/uso terapêutico , Metotrexato/uso terapêutico , Abatacepte , Adulto , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico por imagem , Progressão da Doença , Quimioterapia Combinada , Métodos Epidemiológicos , Feminino , Humanos , Imunoconjugados/efeitos adversos , Imunossupressores/uso terapêutico , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Prognóstico , Qualidade de Vida , Radiografia , Resultado do Tratamento
5.
Ann Rheum Dis ; 68(2): 216-21, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18388156

RESUMO

OBJECTIVE: To determine if treatment with a B cell-targeted therapy can inhibit the progression of structural joint damage in patients with rheumatoid arthritis (RA), exhibiting an inadequate response to tumour necrosis factor (TNF) inhibitors. METHODS: In this phase III study, patients with an inadequate response to a TNF inhibitor and receiving methotrexate were randomised to rituximab or placebo. Radiographs were obtained at baseline, week 24 and week 56 after randomisation. Patients with an inadequate response to their randomised therapy could receive rescue medication from week 16. From week 24, eligible patients from both treatment arms could receive open-label rituximab. Patients were analysed according to their original treatment group. Radiographs were scored using the Genant-modified Sharp method. The primary radiographic endpoint was change in total Genant-modified Sharp score at week 56. RESULTS: Rituximab treatment caused significant reduction in joint damage progression compared with placebo. The mean change from baseline in the total Genant-modified Sharp score at week 56 was significantly lower for patients treated with rituximab than for patients treated with placebo (1.00 vs 2.31; p = 0.005), and was supported by changes in erosion score (0.59 and 1.32 for rituximab plus methotrexate vs placebo plus methotrexate, respectively; p = 0.011) and joint space narrowing score (0.41 and 0.99, respectively; p<0.001). CONCLUSIONS: This study provides the first evidence that a B cell-targeted therapy-rituximab-can significantly inhibit the progression of structural joint damage in patients with RA with long-standing, active and treatment-resistant disease.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anticorpos Monoclonais Murinos , Artrite Reumatoide/diagnóstico por imagem , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Radiografia , Rituximab , Índice de Gravidade de Doença , Resultado do Tratamento
6.
Osteoarthritis Cartilage ; 15(1): 98-103, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16890461

RESUMO

OBJECTIVE: To investigate, over 1-year, the relationship between X-ray and magnetic resonance imaging (MRI) findings in patients with knee osteoarthritis (OA). METHODS: Sixty-two osteoarthritic patients (46 women) were followed for 1 year. At baseline and after 1 year, volume and thickness of cartilage of the medial tibia, the lateral tibia and the femur were assessed by MRI. A global score from the multi-feature whole-organ MRI scoring system (WORMS) was calculated for each patient at baseline and after 1 year. This score combined individual scores for articular cartilage, osteophytes, bone marrow abnormality, subchondral cysts and bone attrition in 14 locations. It also incorporated scores for the medial and lateral menisci, anterior and posterior cruciate ligaments, medial and lateral collateral ligaments and synovial distension. Lateral and medial femoro-tibial joint space width (JSW) measurements, performed by digital image analysis, were assessed from fixed-flexion, postero-anterior knee radiographs. RESULTS: One-year changes in medial femoro-tibial JSW reach 6.7 (20.5) % and changes in medial cartilage volume and thickness reach 0.4 (16.7) % and 2.1 (11.3) %, respectively. Medial femoro-tibial joint space narrowing (JSN) after 1 year, assessed by radiography, was significantly correlated with a loss of medial tibial cartilage volume (r=0.25, P=0.046) and medial tibial cartilage thickness (r=0.28, P=0.025), over the same period. We found also a significant correlation between the progression of the WORMS and radiographic medial JSN over 1 year (r=-0.35, P=0.006). All these results remained statistically significant after adjusting for age, sex and body mass index. CONCLUSION: This study shows a moderate but significant association between changes in JSW and changes in cartilage volume or thickness in knee joint of osteoarthritic patients.


Assuntos
Cartilagem Articular/patologia , Osteoartrite/patologia , Idoso , Cartilagem Articular/diagnóstico por imagem , Estudos de Coortes , Progressão da Doença , Feminino , Fêmur , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Osteoartrite/diagnóstico por imagem , Radiografia , Tíbia
7.
Arthritis Rheum ; 54(12): 3761-73, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17133543

RESUMO

OBJECTIVE: More timely and effective therapy for rheumatoid arthritis (RA) has contributed to increasing rates of clinical remission. However, progression of structural damage may still occur in patients who have satisfied remission criteria, which suggests that there is ongoing disease activity. This questions the validity of current methods of assessing remission in RA. The purpose of this study was to test the hypothesis that modern joint imaging improves the accuracy of remission measurement in RA. METHODS: We studied 107 RA patients receiving disease-modifying antirheumatic drug therapy who were judged by their consultant rheumatologist to be in remission and 17 normal control subjects. Patients underwent clinical, laboratory, functional, and quality of life assessments. The Disease Activity Score 28-joint assessment and the American College of Rheumatology remission criteria, together with strict clinical definitions of remission, were applied. Imaging of the hands and wrists using standardized acquisition and scoring techniques with conventional 1.5T magnetic resonance imaging (MRI) and ultrasonography (US) were performed. RESULTS: Irrespective of which clinical criteria were applied to determine remission, the majority of patients continued to have evidence of active inflammation, as shown by findings on the imaging assessments. Even in asymptomatic patients with clinically normal joints, MRI showed that 96% had synovitis and 46% had bone marrow edema, and US showed that 73% had gray-scale synovial hypertrophy and 43% had increased power Doppler signal. Only mild synovial thickening was seen in 3 of the control subjects (18%), but no bone marrow edema. CONCLUSION: Most RA patients who satisfied the remission criteria with normal findings on clinical and laboratory studies had imaging-detected synovitis. This subclinical inflammation may explain the observed discrepancy between disease activity and outcome in RA. Imaging assessment may be necessary for the accurate evaluation of disease status and, in particular, for the definition of true remission.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Sinovite/diagnóstico , Sinovite/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/complicações , Medula Óssea/patologia , Progressão da Doença , Feminino , Nível de Saúde , Humanos , Articulações/diagnóstico por imagem , Articulações/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Indução de Remissão , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Sinovite/etiologia , Ultrassonografia Doppler
8.
Osteoarthritis Cartilage ; 14 Suppl A: A95-111, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16750915

RESUMO

One of the critical challenges in developing structure-modifying therapies for arthritis, especially osteoarthritis (OA), is measuring changes in progression of joint destruction. Magnetic resonance imaging (MRI) offers considerable promise in this regard. Not only can MRI quantify articular cartilage volume and morphology with high precision and accuracy, but it can also examine several other important articular components, and thus offer a unique opportunity to evaluate the knee and other joints as whole organs. On December 5 and 6, 2002, OMERACT (Outcome Measures in Rheumatology Clinical Trials) and OARSI (Osteoarthritis Research Society International), with support from various pharmaceutical companies listed at the beginning of this supplement, held a Workshop for Consensus on Osteoarthritis Imaging in Bethesda, MD. The aim of the Workshop was to provide a state-of-the-art review of imaging outcome measures for OA of the knee to help guide scientists and pharmaceutical companies who want to use MRI in multi-site studies of OA. Applications of MRI were initially reviewed by a multidisciplinary, international panel of expert scientists and physicians from academia, the pharmaceutical industry and regulatory agencies. The findings of the panel were then presented to a wider group of participants for open discussion. The following report summarizes the results of these discussions with respect to MRI acquisition techniques for whole-organ assessment of the knee in OA. The discussion reviews the selection and qualification of imaging sites for clinical trials, designing imaging protocols for whole-organ assessment of OA, and key considerations in image quality (IQ) control and data management.


Assuntos
Articulação do Joelho/patologia , Imageamento por Ressonância Magnética/métodos , Osteoartrite do Joelho/patologia , Medula Óssea/patologia , Doenças da Medula Óssea/patologia , Cartilagem Articular/patologia , Protocolos Clínicos , Humanos , Ligamentos Articulares/patologia , Meniscos Tibiais/patologia , Membrana Sinovial/patologia , Sinovite/patologia
9.
Osteoarthritis Cartilage ; 14 Suppl A: A116-21, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16678453

RESUMO

OBJECTIVE: The ability to reliably quantify all the structural abnormalities in osteoarthritis (OA) of the knee is a long-standing goal of OA research. On December 5 and 6, 2002, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society, International held a Workshop for Consensus on Osteoarthritis Imaging in Bethesda, MD, with the aim of providing a state-of-the-art review of imaging outcome measures for OA of the knee. As part of the Workshop, data from previous clinical trials and epidemiological studies of OA were analysed with respect to the metrological properties of the measurement methods used. The following report outlines the results of analyses aimed at evaluating the internal construct validity of a whole-organ, ordinal (semi-quantitative) magnetic resonance imaging score (WORMS) using Rasch analysis. The fit of data to the Rasch model offers a measure of the validity of summing different items into a subscale score and the degree to which this score behaves as a unidimensional, interval level measurement tool. METHODS: The Rasch model was applied in two OA studies. The first was a clinical cohort comprising OA knee subjects entering a clinical trial; study entry criteria included patients with at least moderate pain, radiographic osteophytes and a minimum of 1.5mm tibiofemoral joint-space width. The second cohort was from the Boston Osteoarthritis Knee Study, an observational cohort of subjects with symptomatic knee OA with pain on most days and a definite osteophyte in either the tibiofemoral or patellofemoral joints. Baseline WORMS scores from both studies were used for the Rasch analysis, performed with RUMM 2020 software. RESULTS: There was a substantial proportion of subjects in both study populations with zero scores in several of the subscales of WORMS. Few of the subscales met the requirements of the Rasch measurement model when summated across all sites, and summations of some postulated compartmentally based sites also failed to fit the Rasch model. The existing scoring categories also required rescoring at many sites. CONCLUSION: There remain important issues in constructing outcome measurements that summate different features across multiple anatomical sites. The whole-organ scoring system evaluated here is no exception. Resolving these issues will improve the ability of imaging studies to assess complex pathological structural change.


Assuntos
Articulação do Joelho/patologia , Imageamento por Ressonância Magnética/métodos , Osteoartrite do Joelho/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças da Medula Óssea/patologia , Osso e Ossos/patologia , Cartilagem Articular/patologia , Ensaios Clínicos como Assunto , Estudos de Coortes , Edema/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Probabilidade
10.
Osteoarthritis Cartilage ; 14(10): 1033-40, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16713310

RESUMO

INTRODUCTION: Pain is the most common symptom in knee osteoarthritis (OA), a leading cause of chronic disability, and a major source of the disability attributable to OA in general. Pain severity in knee OA is variable, ranging from barely perceptible to immobilizing. The knee lesions that contribute to pain severity have received little attention. OBJECTIVE: To examine whether worse pathology of specific knee tissues - i.e. cartilage, bone (attrition, cysts, bone marrow lesions, and osteophytes), menisci (tears and subluxation), ligaments, and synovium (synovitis/effusion) - is associated with more severe knee pain. METHODS: One hundred and forty-three individuals were recruited from the community with primary (idiopathic) knee OA, with definite tibiofemoral osteophytes in at least one knee, and at least some difficulty with knee-requiring activity. Knee magnetic resonance (MR) images were acquired using coronal T1-weighted spin-echo (SE), sagittal fat-suppressed dual-echo turbo SE, and axial and coronal fat-suppressed, T1-weighted 3D-fast low angle shot (FLASH) sequences. The whole-organ magnetic resonance imaging (MRI) scoring (WORMS) method was used to score knee tissue status. Since summing tissue scores across the entire joint, including regions free of disease, may dilute the ability to detect a true relationship between that tissue and pain severity, we used the score from the worst compartment (i.e. with the poorest cartilage morphology) as our primary approach. Knee pain severity was measured using knee-specific, 100 mm visual analogue scales. In analyses to evaluate the relationship between knee pain severity and lesion score, median quantile regression was used, adjusting for age and body mass index (BMI), in which a 95% CI excluding 0 is significant. RESULTS: The increase in median pain from median quantile regression, adjusting for age and BMI, was significant for bone attrition (1.91, 95% confidence interval (CI) 0.68, 3.13), bone marrow lesions (3.72, 95% CI 1.76, 5.68), meniscal tears (1.99, 95% CI 0.60, 3.38), and grade 2 or 3 synovitis/effusion vs grade 0 (9.82, 95% CI 0.38, 19.27). The relationship with pain severity was of borderline significance for osteophytes and cartilage morphology and was not significant for bone cysts or meniscal subluxation. Ligament tears were too infrequent for meaningful analysis. When compared to the pain severity in knees with high scores for both bone attrition and bone marrow lesions (median pain severity 40 mm), knees with high attrition alone (30 mm) were not significantly different, but knees with high bone marrow lesion without high attrition scores (15 mm) were significantly less painful. CONCLUSION: In persons with knee OA, knee pain severity was associated with subarticular bone attrition, bone marrow lesions, synovitis/effusion, and meniscal tears. The contribution of bone marrow lesions to pain severity appeared to require the presence of bone attrition.


Assuntos
Articulação do Joelho/patologia , Osteoartrite do Joelho/patologia , Dor/patologia , Idoso , Cistos Ósseos/patologia , Doenças da Medula Óssea/patologia , Cartilagem Articular/patologia , Feminino , Humanos , Ligamentos Articulares/patologia , Imageamento por Ressonância Magnética , Masculino , Meniscos Tibiais/patologia , Medição da Dor , Sinovite/patologia
11.
Arthritis Rheum ; 52(9): 2822-9, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16145678

RESUMO

OBJECTIVE: Using radiography to assess the efficacy of a disease-modifying osteoarthritis (OA) drug on joint structure is challenging. Subchondral bone marrow abnormalities determined by magnetic resonance imaging (MRI) and urinary excretion of C-terminal crosslinking telopeptide of type II collagen (CTX-II) have recently been shown to be predictors of radiographic progression in patients with knee OA, suggesting that these may represent valuable biomarkers with increased sensitivity compared with findings on radiography. The aims of this investigation were to analyze, in patients with knee OA, whether the values associated with these 2 OA biomarkers can change within 3 months, and to investigate the relationships between bone marrow abnormalities and CTX-II. METHODS: Knee MRI scans were obtained in 377 patients with painful knee OA (76% women, mean age 63 years, mean disease duration 6.6 years) at both baseline and 3 months. The femoral and tibial condyles and the patella were divided into 8 sites for the scoring of bone marrow abnormalities. A bone marrow abnormality was defined as an area of increased signal on T2-weighted images of the subchondral bone. All scans were reviewed centrally and scored by a single trained radiologist using a validated 4-point scoring method. Fasting urine and serum samples were also collected from all patients at baseline, month 1, month 2, and month 3, in order to measure the levels of urinary CTX-II and serum CTX-I, a biochemical marker of bone resorption. RESULTS: At baseline, 82% of patients had MRI evidence of bone marrow abnormalities. Bone marrow abnormality scores correlated significantly with CTX-II levels (P < 0.0001). Within 3 months, the bone marrow abnormality score decreased in 37 patients (9.8%), increased in 71 patients (18.8%), and did not change in the majority of patients (71.4%). Patients with baseline urinary CTX-II levels in the highest tertile had a relative risk of 2.4 (95% confidence interval 1.1-5.0) of worsening bone marrow abnormalities at 3 months compared with patients with levels in the lowest tertile, after adjustment for age, sex, and body mass index. In patients who showed a decrease in the bone marrow abnormality score at 3 months, urinary CTX-II levels decreased significantly (mean -75 ng/mmole creatinine), whereas levels increased (mean +23 ng/mmole creatinine) in patients showing an increase in the bone marrow abnormality score (P = 0.01 between the 2 groups). No significant association between bone marrow abnormalities and serum CTX-I was observed. CONCLUSION: In patients with painful knee OA, bone marrow abnormalities on MRI can change within only 3 months in approximately 30% of patients. Reduction in the extent of bone marrow abnormalities is associated with a decrease in cartilage degradation.


Assuntos
Medula Óssea/patologia , Colágeno Tipo II/metabolismo , Articulação do Joelho/patologia , Osteoartrite do Joelho/diagnóstico , Biomarcadores/metabolismo , Medula Óssea/metabolismo , Colágeno/sangue , Colágeno Tipo I , Feminino , Fêmur/patologia , Humanos , Cooperação Internacional , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/metabolismo , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/fisiopatologia , Medição da Dor , Patela/patologia , Peptídeos/sangue , Radiografia , Índice de Gravidade de Doença , Tíbia/patologia
13.
Osteoarthritis Cartilage ; 12(3): 177-90, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14972335

RESUMO

OBJECTIVES: To describe a semi-quantitative scoring method for multi-feature, whole-organ evaluation of the knee in osteoarthritis (OA) based on magnetic resonance imaging (MRI) findings. To determine the inter-observer agreement of this scoring method. To examine associations among the features included in the scoring method. METHODS: Nineteen knees of 19 patients with knee OA were imaged with MRI using conventional pulse sequences and a clinical 1.5 T MRI system. Images were independently analyzed by two musculoskeletal radiologists using a whole-organ MRI scoring method (WORMS) that incorporated 14 features: articular cartilage integrity, subarticular bone marrow abnormality, subarticular cysts, subarticular bone attrition, marginal osteophytes, medial and lateral meniscal integrity, anterior and posterior cruciate ligament integrity, medial and lateral collateral ligament integrity, synovitis/effusion, intraarticular loose bodies, and periarticular cysts/bursitis. Intraclass correlation coefficients (ICC) were determined for each feature as a measure of inter-observer agreement. Associations among the scores for different features were expressed as Spearman Rho. RESULTS: All knees showed structural abnormalities with MRI. Cartilage loss and osteophytes were the most prevalent features (98% and 92%, respectively). One of the least common features was ligament abnormality (8%). Inter-observer agreement for WORMS scores was high (most ICC values were >0.80). The individual features showed strong inter-associations. CONCLUSION: The WORMS method described in this report provides multi-feature, whole-organ assessment of the knee in OA using conventional MR images, and shows high inter-observer agreement among trained readers. This method may be useful in epidemiological studies and clinical trials of OA.


Assuntos
Osteoartrite do Joelho/diagnóstico , Índice de Gravidade de Doença , Idoso , Cartilagem Articular/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Osteoartrite do Joelho/patologia
14.
Semin Musculoskelet Radiol ; 5(4): 365-78, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11745051

RESUMO

There have been numerous advances in cartilage imaging with magnetic resonance imaging (MRI) over the past several years. However, in the absence of effective treatments for articular cartilage disease, these innovations have had little applicability to clinical practice. Putative new therapies do exist but only in clinical trials aimed at establishing the efficacy and safety of these therapies before they are released into general use. These trials, therefore, represent the earliest opportunity to develop imaging methods specifically for such therapies and the diseases that they treat. Accordingly, it is the commercial, regulatory, and logistical demands of the clinical trials process, rather than those of clinical practice, that ultimately shape the early evolution of these imaging tools. Understanding this process and its priorities is essential to contributing to this development and to keeping radiology in sync with advances in the rest of medicine. The following article reviews this novel pathway for innovation in medical imaging and reflects on how recent advances in cartilage MRI might fit in.


Assuntos
Doenças das Cartilagens/terapia , Cartilagem Articular/patologia , Ensaios Clínicos como Assunto , Artropatias/terapia , Imageamento por Ressonância Magnética , Biomarcadores/análise , Doenças das Cartilagens/diagnóstico , Determinação de Ponto Final , Humanos , Artropatias/diagnóstico , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/estatística & dados numéricos , Projetos de Pesquisa
15.
J Rheumatol ; 28(5): 1134-42, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11361203

RESUMO

The performance of alternative imaging endpoints in clinical trials can be compared in terms of validity, rate of change, measurement precision, and convenience and cost. With respect to technical performance, magnetic resonance imaging (MRI) appears to show greater sensitivity than radiography for detecting bone abnormalities in rheumatoid arthritis (RA). In addition to monitoring changes in the bones, cartilage, and synovium, MRI can directly visualize the full spectrum of tendon pathology, and has been shown to identify tendonitis and tendon rupture with greater accuracy than clinical examination. MRI is currently regarded to be the most sensitive imaging technique for identifying trauma, infection, ischemia, and primary and secondary neoplasia of bone. Several studies have also shown MRI to be highly sensitive for detecting what appear to be bone erosions in the hands and wrists of patients with RA. MRI shows remarkable promise as a tool for identifying and monitoring structural damage in the joints of patients with RA. MRI appears to be able to identify bone erosions with greater sensitivity than radiography, and to disclose edema-like changes in the marrow, which may precede actual erosion formation. As new therapies with structure modifying capabilities enter the clinic, the ability to identify patients appropriate for those therapies and then to monitor the effectiveness and safety of treatment become increasingly important.


Assuntos
Artrite Reumatoide/patologia , Imageamento por Ressonância Magnética/tendências , Humanos , Imageamento por Ressonância Magnética/instrumentação
16.
Magn Reson Imaging Clin N Am ; 8(2): 409-30, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10819921

RESUMO

Powerful techniques with MR imaging are being developed for evaluating articular cartilage. Pharmaceutical and biotechnology development is driven largely by the search for novel therapeutic solutions to the growing problem of arthritis in our aging society. Accordingly, imaging tools that will be used to direct patients to specific therapies and then to monitor treatment effectiveness and safety presently are being refined and validated in rigorous multicenter and multinational clinical trials aimed at gaining regulatory approval. As trials approach completion, radiologists can anticipate an increased demand for expertise and experience in evaluating articular cartilage disorders. This article reviews this novel mechanism for evolving imaging techniques for clinical use through clinical drug trials, lists the most promising MR imaging markers available for evaluating cartilage integrity, and speculates on how these techniques will find their way into clinical practice.


Assuntos
Doenças das Cartilagens/patologia , Cartilagem Articular/patologia , Imageamento por Ressonância Magnética , Humanos
17.
AJR Am J Roentgenol ; 172(4): 1073-80, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10587150

RESUMO

OBJECTIVE: The purpose of this study was to assess the accuracy of routine T2-weighted MR imaging in detecting and grading articular cartilage lesions in the knee compared with arthroscopy. SUBJECTS AND METHODS: We examined 130 consecutive patients who underwent MR imaging and arthroscopy of the knee for suspected internal derangement. MR imaging consisted of axial and coronal T2-weighted fast spin-echo sequences with fat saturation and sagittal T2-weighted spin-echo sequences. Each single plane was evaluated and graded for the presence and appearance of articular cartilage defects using a standard arthroscopic grading scheme adapted to MR imaging. RESULTS: Of the 86 arthroscopically proven abnormalities, 81 were detected on MR imaging. Sensitivity of the T2-weighted fast spin-echo sequence with fat saturation was 61% for the coronal plane alone and 59% for the axial plane alone. Specificity for each plane was 99%. Sensitivity for the sagittal T2-weighted spin-echo sequence was 40%, and specificity was 100%. Sensitivity of the combination of axial and coronal T2-weighted fast spin-echo sequences with fat saturation and sagittal T2-weighted spin-echo sequence compared with arthroscopy for revealing cartilage lesions was 94%, specificity was 99%, and accuracy was 98%. Sensitivity of coronal and axial T2-weighted fast spin-echo sequences with fat saturation was 93%, and specificity was 99%. Fifty-five lesions (64%) were identically graded on MR imaging and arthroscopy. Seventy-eight lesions (90%) were within one grade using MR imaging and arthroscopy, and 84 lesions (97%) were within two grades using MR imaging and arthroscopy. CONCLUSION: T2-weighted fast spin-echo MR imaging with fat saturation is an accurate and fast technique for detecting and grading articular cartilage defects in the knee. The combination of the axial and coronal planes offers sufficient coverage of articular surfaces to provide a high sensitivity and specificity for chondral defects.


Assuntos
Artroscopia , Cartilagem Articular/patologia , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética , Adulto , Idoso , Doenças das Cartilagens/diagnóstico , Feminino , Humanos , Artropatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade
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