Estudios primarios incluidos en esta revisión sistemática

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Estudio primario

No clasificado

Soluble macrophage biomarkers indicate inflammatory phenotypes in patients with knee osteoarthritis.

Revista Arthritis & rheumatology (Hoboken, N.J.)
Año 2015
Enlaces Pubmed DOI PubMed Central

Este artículo está incluido en 1 Revisión sistemática Revisiones sistemáticas (1 referencia)

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OBJECTIVE: To evaluate the ability of the macrophage markers CD163 and CD14 to predict different osteoarthritis (OA) phenotypes defined by severity of joint inflammation, radiographic features and progression, and joint pain. METHODS: We evaluated 2 different cohorts totaling 184 patients with radiographic knee OA. These included 25 patients from a cross-sectional imaging study for whom there were data on activated macrophages in the knee joint, and 159 patients (134 with 3-year longitudinal data) from the longitudinal Prediction of Osteoarthritis Progression study. Multivariable linear regression models with generalized estimating equations were used to assess the association of CD163 and CD14 in synovial fluid (SF) and blood with OA phenotypic outcomes. Models were adjusted for age, sex, and body mass index. P values less than or equal to 0.05 were considered significant. RESULTS: SF CD14, SF CD163, and serum CD163 were associated with the abundance of activated macrophages in the knee joint capsule and synovium. SF CD14 was positively associated with severity of joint space narrowing and osteophytes in both cohorts. SF and plasma CD14 were positively associated with self-reported knee pain severity in the imaging study. Both SF CD14 and SF CD163 were positively associated with osteophyte progression. CONCLUSION: Soluble macrophage biomarkers reflected the abundance of activated macrophages and appeared to mediate structural progression (CD163 and CD14) and pain (CD14) in OA knees. These data support the central role of inflammation as a determinant of OA severity, progression risk, and clinical symptoms, and they suggest a means of readily identifying a subset of patients with an active inflammatory state and worse prognosis.

Estudio primario

No clasificado

Alpha C-telopeptide of type I collagen is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis.

Revista Arthritis & rheumatology (Hoboken, N.J.)
Año 2014
Enlaces Pubmed DOI PubMed Central

Este artículo está incluido en 1 Revisión sistemática Revisiones sistemáticas (1 referencia)

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OBJECTIVE: To evaluate joint tissue remodeling using the urinary collagen biomarkers urinary α-C-telopeptide of type I collagen (α-CTX) and urinary C-telopeptide of type II collagen (CTX-II) and to determine the association of these biomarkers with osteoarthritis (OA) severity, progression, and localized knee bone turnover. METHODS: Participants (n = 149) with symptomatic and radiographic knee OA underwent fixed-flexion knee radiography at baseline and 3 years, and late-phase bone scintigraphy of both knees at baseline, which were scored semiquantitatively for osteophyte and joint space narrowing (JSN) severity and uptake intensity, with scores summed across knees. Urinary concentrations of α-CTX and CTX-II were determined by enzyme-linked immunosorbent assay. Immunohistochemical analysis of human OA knees was performed to localize the joint tissue origin of the biomarker epitopes. RESULTS: Urinary α-CTX concentrations correlated strongly with the intensity of bone scintigraphic uptake and with JSN progression (risk ratio 13.2) and osteophyte progression (risk ratio 3). Urinary CTX-II concentrations were strongly associated with intensity of bone scintigraphic uptake, with JSN and osteophyte severity, and with OA progression based on osteophyte score. Urinary α-CTX localized primarily to high bone turnover areas in subchondral bone. CTX-II localized to the bone-cartilage interface, the tidemark, and damaged articular cartilage. CONCLUSION: Baseline urinary α-CTX, which was localized to high turnover areas of subchondral bone, was associated with dynamic bone turnover of knees, as signified by scintigraphy, and progression of both osteophytes and JSN. Urinary CTX-II correlated with JSN and osteophyte severity and progression of osteophytes. To our knowledge, this represents the first report of serologic markers reflecting subchondral bone turnover. These collagen markers may be useful for noninvasive detection and quantification of active subchondral bone turnover and joint remodeling in knee OA.

Estudio primario

No clasificado

The value of cartilage biomarkers in progressive knee osteoarthritis: cross-sectional and 6-year follow-up study in middle-aged subjects.

Autores Kumm J , Tamm A , Lintrop M , Tamm A
Revista Rheumatology International
Año 2013

Este artículo está incluido en 1 Revisión sistemática Revisiones sistemáticas (1 referencia)

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Estudio primario

No clasificado

Reemplazo total de rodilla como resultado de la osteoartritis de la rodilla: Predictores deriva de una observación a largo plazo de 4 años siguientes un ensayo clínico aleatorizado Uso de sulfato de condroitina.

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Revista Cartilage
Año 2013
Enlaces Pubmed DOI PubMed Central

Este artículo está incluido en 2 Revisiones sistemáticas Revisiones sistemáticas (2 referencias) 1 Síntesis amplia Síntesis amplias (1 referencia)

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OBJETIVO: predecir, a partir de datos clínicos y qMRI, la incidencia de reemplazo total de rodilla (PTR) durante el largo plazo de seguimiento de la osteoartritis de rodilla (OA) de los pacientes que anteriormente recibieron sulfato de condroitina (CS) o el tratamiento con placebo. DISEÑO: Un análisis post hoc por intención de tratar de evaluar la incidencia de TKR se realizó en pacientes con artrosis de rodilla que habían participado en un ensayo de 12 meses para evaluar el impacto de CS (800 mg / día) frente a placebo durante 6 meses, seguido por una fase abierta de 6 meses en el que todos los pacientes recibieron CS. Además, se determinaron los predictores clínicos y qMRI de TKR. RESULTADOS: Trece TKRs se realizaron en la población después de un 4-años de seguimiento. Más TKRs se realizaron en el grupo placebo que en el grupo CS (69% vs. 31%, P = 0,150, regresión logística). Los predictores estadísticamente significativos de TKRs eran, al inicio del estudio, el aumento de dolor y función WOMAC puntajes, la presencia de lesiones de médula ósea (BMLS), y mayores niveles de proteína C reactiva. La pérdida de volumen del cartílago medial y aumento del dolor WOMAC y la función en un año también fueron predictores de TKR. El análisis multifactorial reveló que la presencia de la línea de base y superior BML puntuación de dolor WOMAC fueron predictores independientes. Es hora de ocurrencia del TKR también favoreció al grupo CS versus placebo (log-rank, p = 0,094). CONCLUSIÓN: Los síntomas como dolor en la rodilla y la función, la presencia de BML, y la pérdida de volumen del cartílago predicen la aparición a largo plazo de un resultado "dura", como TKR.

Estudio primario

No clasificado

Skin pentosidine in very early hip/knee osteoarthritis (CHECK) is not a strong independent predictor of radiographic progression over 5 years follow-up.

Revista Osteoarthritis and cartilage
Año 2013
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Este artículo está incluido en 2 Revisiones sistemáticas Revisiones sistemáticas (2 referencias)

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OBJECTIVES: Age-related changes in articular cartilage are likely to play a role in the etiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced glycation end products (AGEs). The present study evaluates whether pentosidine can predict radiographic progression and/or burden over 5 years follow-up in a cohort of early knee and/or hip OA. DESIGN: The 5 years follow-up data of 300 patients from cohort hip & cohort knee (CHECK) were used. Radiographic progression and burden were assessed by X-rays of both knees and hips (Kellgren and Lawrence (K&L) and Altman scores). Baseline pentosidine levels (and urinary CTXII as a comparator) were measured by high-performance-liquid-chromatography (HPLC) and enzyme linked immunosorbent assay (ELISA). Univariable and multivariable associations including baseline radiographic damage, age, gender, body mass index (BMI) and kidney function were performed. RESULTS: Both pentosidine and urinary C-terminal telopeptide of type II collagen (uCTXII) correlated with radiographic progression and burden. In general pentosidine did not have an added predictive value to uCTXII for progression nor burden of the disease. The best prediction was obtained for burden of radiographic damage (R(2) = 0.60-0.88), bus this was predominantly determined by baseline radiographic damage (without this parameter R(2) = 0.07-0.17). Interestingly, pentosidine significantly added to prediction of osteophyte formation, whereas uCTXII significantly added to prediction of JSN in multivariable analysis. CONCLUSION: Pentosidine adds to prediction of radiographic progression and burden of osteophyte formation and uCTXII to radiographic progression and burden of JSN, but overall skin pentosidine did not perform better that uCTXII in predicting radiographic progression or burden. Burden of damage over 5 years is mainly determined by radiographic joint damage at baseline.

Estudio primario

No clasificado

Association between cartilage and bone biomarkers and incidence of radiographic knee osteoarthritis (RKOA) in UK females: a prospective study.

Revista Osteoarthritis and cartilage
Año 2013
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Este artículo está incluido en 3 Revisiones sistemáticas Revisiones sistemáticas (3 referencias)

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OBJECTIVE: There is a need to find biochemical markers that would identify people with increased risk of developing radiographic knee osteoarthritis (RKOA). The aim of this study was to evaluate the ability of cartilage and bone biomarkers (cartilage oligomeric matrix protein (COMP), aggrecan, cellular inhibitor of apoptosis protein (cIAP), N-telopeptide-to-helix (NTx)) to predict RKOA incidence in a 10-year follow-up of UK females from the Chingford community study. METHOD: Joint space narrowing (JSN), osteophytes (OSP) and Kellgren-Lawrence (K/L) grades were scored from radiographs of both knees at study baseline and 10 years later in 1,003 women aged 45-64. Circulating levels of biomarkers and demographic variables were measured at baseline. Statistical association analysis was conducted between the potential predictor factors measured at baseline and documentation of RKOA at 10-year follow-up. RESULTS: Age and body mass index (BMI), were significant predictors of incidence of RKOA as assessed by K/L and OSP. Considering biomarkers, independent significant association was found between COMP circulating levels and K/L scores (Odd Ratio (OR) = 2.87, 95% Confidence Interval (CI) = 1.19-6.89, P = 0.018). Significant negative association was detected between aggrecan plasma concentrations and JSN, with OR = 0.37 (95% CI 0.15-0.89), P = 0.026. CONCLUSIONS: Aggrecan and COMP circulating levels contribute to identification of phenotype-specific RKOA incidence. These data suggest potentially protective role of aggrecan in cartilage loss, as measured by JSN. High COMP levels are risk factors for development of RKOA, as assessed by K/L scores.

Estudio primario

No clasificado

Cross-sectional and predictive associations between plasma adipokines and radiographic signs of early-stage knee osteoarthritis: data from CHECK.

Revista Osteoarthritis and cartilage
Año 2012
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OBJECTIVE: To investigate cross-sectional and predictive associations of plasma adipokines with biochemical markers of systemic joint metabolism and radiographic signs of early-stage knee osteoarthritis (OA). DESIGN: The adipokines pLeptin, pAdiponectin, and pResistin, the cartilage markers C-terminal telopeptide of type II collagen (uCTX-II), N-terminal propeptide of type IIA procollagen (sPIIANP), chondroitin sulfate 846 (sCS846), and cartilage oligomeric matrix protein (sCOMP), and the synovial markers hyaluronic acid (sHA) and N-terminal propeptide of type III procollagen (sPIIINP) were assessed by enzyme-linked immunosorbent assay or radioactive immunoassay in baseline samples of Cohort Hip and Cohort Knee (CHECK), a cohort of 1002 subjects with early-stage symptomatic knee and/or hip OA. Knee radiographs were obtained at baseline and after 2 and 5 years and scored according to Kellgren & Lawrence. RESULTS: pLeptin showed positive associations with uCTX-II, sCOMP, sPIIANP, sHA, and sPIIINP, and with presence and progression of radiographic knee OA. Associations expectedly disappeared after adjustment for body mass index. pResistin showed positive associations with sPIIINP and present and incident radiographic knee OA that were largely independent of BMI. pAdiponectin showed positive associations with uCTX-II and sCOMP. Furthermore, pAdiponectin did not show associations with radiographic knee OA on itself, but associations of pResistin with present radiographic knee OA were stronger in higher pAdiponectin tertiles (P = 0.024 for interaction between pAdiponectin and pResistin). Although statistically significant, all associations were weak. CONCLUSIONS: Adipokines may have aggravating, although may be minor, structural effects in early-stage knee OA.

Estudio primario

No clasificado

Biomarkers of incident radiographic knee osteoarthritis: do they vary by chronic knee symptoms?

Revista Arthritis and rheumatism
Año 2011
Enlaces Pubmed DOI PubMed Central

Este artículo está incluido en 1 Revisión sistemática Revisiones sistemáticas (1 referencia)

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OBJECTIVE: To explore the ability of osteoarthritis (OA)-related biomarkers to predict incident radiographic knee OA in a large sample of African American and Caucasian men and women. METHODS: Baseline levels of serum cartilage oligomeric matrix protein (COMP), hyaluronan (HA), high-sensitivity C-reactive protein (hsCRP), and keratan sulfate (KS) and baseline and followup radiographs were available for 353 knees without baseline osteophyte formation and for 446 knees without baseline joint space narrowing (JSN). Cox models estimated the hazard ratio (HR) and 95% confidence interval (95% CI) for incident knee OA for a 1-unit increase in the ln of each biomarker, with adjustment for age, race, sex, body mass index, and knee OA of the contralateral limb. Report of chronic knee symptoms was explored as a modifier of the association. RESULTS: The hazard of incident knee osteophytes (HR 2.16 [95% CI 1.39-3.37]) and incident JSN (HR 1.82 [95% CI 1.15-2.89]) increased with higher baseline ln(COMP) levels. The hazard of incident knee JSN increased with higher ln(HA) levels (HR 1.46 [95% CI 1.14-1.87]). Baseline ln(hsCRP) and ln(KS) did not predict incident knee outcomes. HRs per unit increase in ln(COMP), ln(HA), and ln(KS) were higher among knees with chronic symptoms than among those without symptoms. CONCLUSION: Higher baseline ln(COMP) and ln(HA) levels were associated with incident knee OA over an average followup period of 6.3 years. These results represent detection of a molecular stage of OA prior to radiographic manifestations. Further exploration is needed to determine how chronic knee symptoms modify the biomarker-incident knee OA association.

Estudio primario

No clasificado

Serum transforming growth factor-beta 1 is not a robust biomarker of incident and progressive radiographic osteoarthritis at the hip and knee: the Johnston County Osteoarthritis Project.

Revista Osteoarthritis and cartilage
Año 2010
Enlaces Pubmed DOI PubMed Central

Este artículo está incluido en 1 Revisión sistemática Revisiones sistemáticas (1 referencia)

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PURPOSE: To test whether serum transforming growth factor-beta 1 (TGF-beta1) predicts incident and progressive hip or knee radiographic OA (rOA). METHODS: Serum TGF-beta1 was measured for 330 participants aged 45 years and older in the Johnston County Osteoarthritis Project, with paired longitudinal films available for 618 hips and 658 knees. Incident and progressive rOA were defined using Kellgren-Lawrence (K-L) grade as well as osteophyte (OST) and joint space narrowing (JSN) scores. Natural logarithm transformation was used to produce near-normal distributions for continuous TGF-beta1 (lnTGF-beta1). Separate multivariable Weibull regression models were used to provide hazard ratios (HRs) for a 1-unit increase lnTGF-beta1 with each rOA outcome, accounting for variable follow-up times and clustering by individual, adjusted for age, race, gender, and body mass index (BMI). Interaction terms were considered statistically significant at P<0.10. RESULTS: The mean (+/-SD) age of the sample was 61.9+/-9.7 years, the mean BMI was 30.3+/-6.9 kg/m(2), with 60.6% women and 42.4% AA. The mean (+/-SD) TGF-beta1 was 17.8+/-6.1 ng/ml; follow-up time was 6.1+/-1.3 years. There were no significant interactions by race or gender. HRs showed no significant relationship between lnTGF-beta1 and incident or progressive rOA, OST, or JSN, at the knee or the hip. CONCLUSIONS: Levels of TGF-beta1 do not predict incident or progressive rOA, OST, or JSN at the hip or knee in this longitudinal, population-based study, making it unlikely that TGF-beta1 will be a robust biomarker for rOA in future studies.

Estudio primario

No clasificado

Increased urinary excretion of C-telopeptides of type II collagen (CTX-II) predicts cartilage loss over 21 months by MRI

Revista Osteoarthritis and cartilage
Año 2009
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Este artículo está incluido en 2 Revisiones sistemáticas Revisiones sistemáticas (2 referencias)

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Objective: Osteoarthritis (OA) is characterized by increased bone and cartilage metabolism leading to joint damage. The urinary excretion of C-telopeptides of type II collagen (CTX-II) has earlier predicted progression in radiographic OA (ROA) - useful for participant selection in clinical studies of potential disease modifying OA drugs (DMOADs). We investigated the longitudinal interrelationship between CTX-II and knee cartilage volume quantified from magnetic resonance imaging (MRI). Methods: We followed 158 subjects [48% females, 36 with knee ROA at baseline (BL)] for 21 months. The Kellgren and Lawrence (KL) index and joint space width were assessed from radiographs (acquired load-bearing, semi-flexed). MRI scans were acquired from a 0.18 T Esaote scanner (40° flip angle (FA), TR 50 ms, TE 16 ms, scan time 10 min, resolution 0.7 mm × 0.7 mm × 0.8 mm) and medial tibial and femoral cartilage volume was quantified. Radiographs and MRI were acquired at BL and follow-up. Fasting morning urine samples (second void) were collected for BL CTX-II measurement. Results: CTX-II was 56% higher in ROA subjects (P = 0.0001). In addition, elevated BL CTX-II was associated with radiographic progression (by KL or joint space narrowing) although not statistically significant. Contrarily, elevated BL CTX-II predicted longitudinal cartilage loss by MRI (middle/high tertiles had odds ratios 4.0/3.9, P < 0.01) corresponding to 3.1% increased yearly cartilage loss. Conclusion: Prognostic markers in study selection criteria must ensure that placebo-treated participants progress to enable efficacy demonstration. And efficacy markers must allow progression detection within the study period. Our results support applying CTX-II for selection of high risk subjects and applying the fully automatic MRI-based framework for quantification of cartilage loss. © 2008 Osteoarthritis Research Society International.