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

Jin, Xingzhong; Beguerie, Julieta Ruíz; Zhang, Weiya; Blizzard, Leigh; Otáhal, Petr; Jones, Graeme; Ding, Changhai

doi:10.1136/annrheumdis-2013-204494

Cited by 218 publications

(170 citation statements)

References 44 publications

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“…Many cohort studies have , making further investigation into this link necessary. A meta-analysis of 32 reported clinical studies by Jin and colleagues further complicates the role of CRP in OA pathogenesis, as it was concluded that lowgrade systemic inflammation may play a more prominent role in symptoms of OA 38 .…”

Section: Discussionmentioning

confidence: 99%

Variable cartilage degradation in mice with diet-induced metabolic dysfunction: food for thought

Kozijn

Gierman

Ham

et al. 2018

Osteoarthritis and Cartilage

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Mouse model s u m m a r yObjective: Human cohort studies have demonstrated a role for systemic metabolic dysfunction in osteoarthritis (OA) pathogenesis in obese patients. To explore the mechanisms underlying this metabolic phenotype of OA, we examined cartilage degradation in the knees of mice from different genetic backgrounds in which a metabolic phenotype was established by various dietary approaches. Design: Wild-type C57BL/6J mice and genetically modified mice (hCRP, LDLr À/À . Leiden and ApoE*3-Leiden.CETP mice) based on C57BL/6J background were used to investigate the contribution of inflammation and altered lipoprotein handling on diet-induced cartilage degradation. High-caloric diets of different macronutrient composition (i.e., high-carbohydrate or high-fat) were given in regimens of varying duration to induce a metabolic phenotype with aggravated cartilage degradation relative to controls. Results: Metabolic phenotypes were confirmed in all studies as mice developed obesity, hypercholesteremia, glucose intolerance and/or insulin resistance. Aggravated cartilage degradation was only observed in two out of the twelve experimental setups, specifically in long-term studies in male hCRP and female ApoE*3Leiden.CETP mice. C57BL/6J and LDLr À/À . Leiden mice did not develop HFD-induced OA under the conditions studied. Osteophyte formation and synovitis scores showed variable results between studies, but also between strains and gender. Conclusions: Long-term feeding of high-caloric diets consistently induced a metabolic phenotype in various C57BL/6J (-based) mouse strains. In contrast, the induction of articular cartilage degradation proved variable, which suggests that an additional trigger might be necessary to accelerate diet-induced OA progression. Gender and genetic modifications that result in a humanized pro-inflammatory state (human CRP) or lipoprotein metabolism (human-E3L.CETP) were identified as important contributing factors. © 2017 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. IntroductionOsteoarthritis (OA) is a progressive joint disease that is characterised by focal loss of articular cartilage, which impedes smooth joint movement and causes stiffness and pain. The most important risk factors for OA are age, gender and obesity. The latter being of specific interest in developed countries, where prolonged life expectancy and a progressive sedentary lifestyle in combination with a high caloric diet is predicted to exponentially increase the number of obese individuals and hence the prevalence of OA The association between knee OA and obesity has been comprehensively studied in humans. Weight loss was found to significantly reduce pain and increase mobility in knee OA patients 3 and reduced the risk of onset of the disease 4 . In obese adults, weight loss combined with exercise appears to be the most promising treatment and is therefore recommended by several international guidelines on the management of metabolic OA 5,6 .Moreover, overweight was found to ...

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Section: Discussionmentioning

confidence: 99%

Variable cartilage degradation in mice with diet-induced metabolic dysfunction: food for thought

Kozijn

Gierman

Ham

et al. 2018

Osteoarthritis and Cartilage

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“…In humans with OA, serum CRP typically ranges from 3,000 to 8,000 μg/L [42]. Several dogs in the present study had serum CRP values >8,000 μg/L, suggesting more severe joint inflammation and greater risk of disease progression [43]. We also found that synovial/serum CRP ratio in partial CR stifles was correlated with progressive CrCL fiber tearing, supporting the concept that CRP reflects severity and progression of synovitis/OA [44,45] and, additionally, non-contact complete CR in dogs.…”

Section: Discussionmentioning

confidence: 98%

Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture

et al. 2016

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Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated stifle osteoarthritis (OA) is an important veterinary health problem. CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR stifle. Blood (entry, 4 and 8 weeks) and stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the stifle joint inflammatory response associated with cranial cruciate ligament matrix degeneration or damage.

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“…While the effect size for CRP was small (Cohen’s d = 0.2), it is interesting to note that the variance in serum levels was relatively small (range 1 to 20 mg/l), which suggests that even small variations in CRP are associated with higher levels of preoperative pain. In a recent systematic review that evaluated for associations between serum levels of CRP and pain, function, and radiographic changes in OA patients compared to healthy controls [22], weak but significant correlations were found between higher CRP levels and higher pain scores as well as decreases in physical function. No correlation was found between CRP levels and radiographic changes, which suggest that low grade systemic inflammation may play a role in patients’ symptom experiences but not in cartilage deterioration.…”

Section: Discussionmentioning

confidence: 99%

“…Creatinine was included in this analysis because patients with higher levels of creatinine (i.e., males >105, females >90) did not receive celecoxib, which may have led to higher postoperative pain. Higher levels of C-reactive protein and obesity are associated with higher levels of pain in patients with OA but the impact on postoperative pain is not known [22]. Lower resting blood pressure levels are been associated with lower acute pain thresholds [23].…”

Section: Methodsmentioning

confidence: 99%

Preoperative Pain, Symptoms, and Psychological Factors related to Higher Acute Pain Trajectories during Hospitalization for Total Knee Arthroplasty

et al. 2016

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ObjectivesUnrelieved postoperative pain after total knee arthroplasty (TKA) is a significant problem. This longitudinal study investigated how preoperative pain intensity, as well as a comprehensive list of preoperative and perioperative factors, influenced the severity of acute average and worst pain after TKA.MethodsPrior to surgery, 203 patients completed a demographic questionnaire, Lee Fatigue Scale, Fatigue Severity Scale, Hospital Anxiety and Depression Scale, and Brief Illness Perception Questionnaire. Brief Pain Inventory was completed prior to surgery as well as through postoperative days (POD) 0 to 4. Clinical data were extracted from medical records.ResultsSeveral factors were associated with higher levels of preoperative and postoperative pain. Lower preoperative average and worst pain intensity scores were associated with increases in average and worst postoperative pain from POD1 to POD4. A higher number of comorbidities, higher C-reactive protein values, and higher pain interference with function were associated with higher preoperative levels of average pain. Older age, higher fatigue levels, and higher scores on identity and emotional responses to osteoarthritis (OA) were associated with higher preoperative levels of worst pain. Lower perceived consequences of OA were associated with higher pain from POD1 to POD4. Males and patients with lower preoperative scores for average pain had higher worst pain following surgery.DiscussionPatients at higher risk for more severe postoperative pain can be identified through an assessment of pain and other risk factors identified in this study. Future research needs to test the efficacy of interventions that modify patients’ perceptions of living with OA and pain intensity before surgery on short and long term postoperative outcomes.

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

Abstract: Low-grade systemic inflammation may play a greater role in symptoms rather than radiographic changes in OA.

Cited by 218 publications

References 44 publications

Variable cartilage degradation in mice with diet-induced metabolic dysfunction: food for thought

Variable cartilage degradation in mice with diet-induced metabolic dysfunction: food for thought

Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture

Preoperative Pain, Symptoms, and Psychological Factors related to Higher Acute Pain Trajectories during Hospitalization for Total Knee Arthroplasty

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