Circulating C-reactive protein in osteoarthritis: a systematic review and meta-analysis

Jin, Xingzhong; Beguerie, Julieta Ruíz; Zhang, W.; Blizzard, Leigh; Otáhal, Petr; Jones, Graeme; Ding, C.

doi:10.1016/j.joca.2014.02.545

Cited by 38 publications

(60 citation statements)

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“…Furthermore, there were significant associations between hsCRP and total WOMAC knee pain and their changes, and the longitudinal association was partly explained by total knee BMLs. These results add to the growing evidence that the clinical course of OA may be associated with systemic inflammation (2,5,10). Several serum biomarkers are known to be correlated with OA incidence and progression and have thus been proposed as diagnostic and prognostic markers for knee OA (28)(29)(30)(31).…”

Section: Discussionsupporting

confidence: 55%

“…A recent meta-analysis found that serum hsCRP levels in people with OA were modestly but significantly higher than in controls and were weakly but significantly associated with knee pain and decreased physical function (10). However, that analysis was based on 5 crosssectional studies, so whether these associations are causal is unknown (10). We reported that serum hsCRP was associated with increased knee pain over 5 years in older adults (11).…”

Section: Introductionmentioning

confidence: 79%

“…It is synthesized by the liver and can be upregulated by IL-6 and IL-1 (7) and is associated with presence and progression of knee OA (8,9). A recent meta-analysis found that serum hsCRP levels in people with OA were modestly but significantly higher than in controls and were weakly but significantly associated with knee pain and decreased physical function (10). However, that analysis was based on 5 crosssectional studies, so whether these associations are causal is unknown (10).…”

Section: Introductionmentioning

confidence: 99%

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Cross‐Sectional and Longitudinal Associations Between Serum Levels of High‐Sensitivity C‐Reactive Protein, Knee Bone Marrow Lesions, and Knee Pain in Patients With Knee Osteoarthritis

Zhu

Jin

Wang

et al. 2016

Arthritis Care & Research

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Objective. To describe associations between serum high-sensitivity C-reactive protein (hsCRP), knee bone marrow lesions (BMLs), and knee pain, cross-sectionally and longitudinally, in patients with knee osteoarthritis (OA). Methods. Patients (n 5 192) with symptomatic knee OA (mean age 63 years, range 50-79, women 53%) were assessed at baseline and after 24 months. Serum hsCRP was measured using enzyme-linked immunosorbent assay. Knee BMLs were scored using the modified Whole-Organ Magnetic Resonance Imaging (MRI) Score from T2-weighted fat-supressed fast spin-echo MRI. Knee pain was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index. Results. Quartiles of baseline serum hsCRP were associated with the presence of knee BMLs (prevalence ratio 1.07 per quartile [95% confidence interval (95% CI) 1.00, 1.15]) and total knee pain scores (b 13.66 per quartile [95% CI 2.26, 25.07]) in multivariable analyses. Longitudinally, higher baseline hsCRP was associated with an increase in BML score (risk ratio 1.37 per quartile [95% CI 1.10, 1.70]), and change in hsCRP was positively associated with change in BML score (b 0.19 [95% CI 0.05, 0.34]) in adjusted analyses. Baseline hsCRP was not associated with change in total knee pain, but change in hsCRP was positively and significantly associated with change in total knee pain (b 4.71 [95% CI 0.48, 8.94]). This became nonsignificant after adjustment for changes in BML score. Conclusion. In patients with knee OA, serum hsCRP is associated with knee BML scores and, to a lesser extent, pain both cross-sectionally and longitudinally, suggesting that inflammation is linked with BMLs and their associated pain.

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Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

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Cross‐Sectional and Longitudinal Associations Between Serum Levels of High‐Sensitivity C‐Reactive Protein, Knee Bone Marrow Lesions, and Knee Pain in Patients With Knee Osteoarthritis

Zhu

Jin

Wang

et al. 2016

Arthritis Care & Research

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“…Indeed, increased activity of HO-1 in immune cells (and possibly other tissue) may account for the significant SCE treatment-associated reduction in serum CRP shown in Fig. 4 (p<0.05), as CRP level is a well-known correlate of the severity of inflammatory diseases, including OA (Jin et al 2013;Kitamura et al 2011). The relevance of increased HO-1 expression and CRP inhibition to OA and other inflammatory diseases is strengthened by earlier studies that demonstrate a close correlation between severity of joint inflammation and levels of HO-1, CRP, and matrix metalloproteinase (a tissue degradative enzyme) in synovial fluid of rheumatoid arthritis patients (Jin et al 2013;Kitamura et al 2011;Bak et al 2003).…”

Section: Effect Of Topical Application Of Sce Emulsion On Serum C-reamentioning

confidence: 96%

“…4 (p<0.05), as CRP level is a well-known correlate of the severity of inflammatory diseases, including OA (Jin et al 2013;Kitamura et al 2011). The relevance of increased HO-1 expression and CRP inhibition to OA and other inflammatory diseases is strengthened by earlier studies that demonstrate a close correlation between severity of joint inflammation and levels of HO-1, CRP, and matrix metalloproteinase (a tissue degradative enzyme) in synovial fluid of rheumatoid arthritis patients (Jin et al 2013;Kitamura et al 2011;Bak et al 2003). These observations further underscore the role of disease-or trauma-related HO-1 expression as a general adaptive response to dysregulated inflammation with therapeutic potential in many clinical venues (Morse and Choi 2002).…”

Section: Effect Of Topical Application Of Sce Emulsion On Serum C-reamentioning

confidence: 98%

Amelioration of human osteoarthritis symptoms with topical ‘biotherapeutics’: a phase I human trial

Mahmoud

Al-Awadhi

Haines

2015

Cell Stress and Chaperones

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Osteoarthritis (OA) treatments presently rely on analgesics, which manage pain but fail to restore imbalances between catabolic and anabolic processes that underlie OA pathogenesis. Recently, biologic (biotherapeutic) drugs, which alter the activity of catabolic agents such as nitric oxide and inflammatory cytokines in ways, allowing tissue regeneration, were evaluated for efficacy in OA treatment. These studies failed to demonstrate dramatic abatement of OA symptoms by these drugs, but suggested strategies by which biologic agents might be used to treat OA. The present review summarizes current understanding of OA pathogenesis and evolving treatments. Preliminary evaluations of a novel biotherapeutic strategy are presented here. Twenty OA patients receiving sour topical cherry seed extract (SCE), an inducer of heme oxygenase-1 (HO-1), a major physiological protectant against oxidative stress exhibited significantly decreased joint pain and activation of CD4+ T cells expressing inflammatory cytokines (p<0.05), significantly decreased peripheral blood C-reactive protein (CRP), and increased leukocyte HO-1 (p<0.05) in comparison with ten placebo-treated patients. SCE inhibits joint-damaging inflammatory mediator production. This agent therefore meets the main criterion for classification as a "biotherapeutic," or "biologic" agent. The negligible toxicity and low cost of such materials make them promising contributors to OA treatment, sustainable within resource limitations of a wide range of patients.

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Association Between Experimental Pain Biomarkers and Serologic Markers in Patients With Different Degrees of Painful Knee Osteoarthritis

Arendt-Nielsen

Eskehave

Egsgaard

et al. 2014

Arthritis & Rheumatology

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Objective. To assess the association between pain mechanisms (sensitization) and biochemical markers for cartilage, bone, and inflammation in patients with knee pain.Methods. The study group comprised 281 patients with different degrees of knee pain intensity and radiographic findings (using the Kellgren/Lawrence [K/L] scale). The following structurally related serologic biomarkers were measured in serum: high-sensitivity C-reactive protein (hsCRP), matrix metalloproteinase (MMP)-mediated breakdown of CRP (CRPM), MMPmediated degradation of type I collagen (C1M), C2M, and C3M. Pressure-pain thresholds (PPT) (peripheral and spreading sensitization), temporal summation of pain, and conditioning pain modulation (CPM) (with the latter 2 biomarkers representing generalized sensitization) were assessed. For each pain parameter, the patients were categorized as most sensitized or least sensitized.Results. Correlations were observed between the pain biomarkers PPT, temporal summation, and CPM and maximal pain intensity during the last 24 hours. Significant associations between most of the serologic biomarkers were observed. A high CRPM level was associated with centralized sensitization (temporal summation and CPM). None of the serologic markers correlated with the intensity or duration of knee pain, and only hsCRP correlated with the K/L grade. The most-sensitized group contained more women than men, and the least-sensitized group contained more men than women.Conclusion. A platform of mechanistic pain biomarkers in combination with structure-related serologic biomarkers provides new possibilities for understanding how osteoarthritis-related structural features may be associated with pain and pain sensitization. This study showed significant correlations between central pain sensitization and CRPM as a possible measure for chronic inflammation. Future pain association studies should include biomarkers representing the local joint environment more specifically.In osteoarthritis (OA), the association between joint damage and pain intensity has not been clearly elucidated (1,2). Although the pain mechanisms and various other factors associated with OA are controversial (3), peripheral and central pain sensitization appear to be involved (4,5). Up to 70% of patients with OA have somatosensory abnormalities (6) involving pain sensitization (7). The implications of sensitization are enhanced responses to a painful stimulation provoked locally (localized peripheral sensitization) and extrasegmentally (central spreading sensitization).Because traditional structural joint markers show

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Circulating C-reactive protein in osteoarthritis: a systematic review and meta-analysis

Cited by 38 publications

References 0 publications

Cross‐Sectional and Longitudinal Associations Between Serum Levels of High‐Sensitivity C‐Reactive Protein, Knee Bone Marrow Lesions, and Knee Pain in Patients With Knee Osteoarthritis

Cross‐Sectional and Longitudinal Associations Between Serum Levels of High‐Sensitivity C‐Reactive Protein, Knee Bone Marrow Lesions, and Knee Pain in Patients With Knee Osteoarthritis

Amelioration of human osteoarthritis symptoms with topical ‘biotherapeutics’: a phase I human trial

Association Between Experimental Pain Biomarkers and Serologic Markers in Patients With Different Degrees of Painful Knee Osteoarthritis

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