| Background Osteoarthritis(OA)is the most common joint disease in the middle-aged and elderly populations.It is characterized by articular cartilage damage,osteophyte formation and other joint structural destruction.The knee joint is one of the most commonly affected joints.Clinical symptoms include joint pain,limited mobility,joint deformity,which seriously affect people's work ability and quality of life.With the the society aging,knee OA is one of the important reasons for the disability of the elderly.Detection of serum biomarkers of OA bone and cartilage metabolism can predict early joint damage,and help us to examine the progress of disease.OA is a metabolic and low-inflammatory disease.Its inflammatory response is related to oxidative stress and deposition of intra-articular crystals including urate and calcium phosphate.Uric Acid(UA)is one of the main endogenous water-soluble antioxidants in the body.When its concentration is increased,it can crystallize in the joints to form crystals.Citrate can increase crystal solubility and inhibit crystal deposition on the joint surface.There were no systematic reports on the relationship of serum uric acid and citrate with the symptoms,joint structural changes and serum biomarkers in knee OA so far.Objective The aims of this study were to investigate relationships between serum uric acid,citrate and knee symptoms,joint structural changes and serum biomarkers in patients with knee osteoarthritis.Methods Two hundred and five patients with symptomatic knee OA enrolled from Department of Rheumatology and Immunology in the First Affiliated Hospital of Anhui Medical University from January 2012 to November 2013 participated in the study.In the study of serum UA,122 patients were finally included,and 137 patients were finally included in the study of citrate due to the lack of relevant examinations.Questionnaires were filled by patients.The Western Ontario and Mc Master Universities(WOMAC)Osteoarthritis Index score was used to assess joint symptoms.Knee radiography was used to assess knee osteophytes(OP),joint space narrowing(JSN)and Kellgren-Lawrence(K-L)grading.Magnetic resonance imaging(MRI)was used to determine knee cartilage volume,cartilage defects(CD),bone marrow lesions(BMLs)and infrapatellar fat pad(IPFP)signal intensity alternation.Enzyme-linked immunosorbent assay was used to measured serum biomarkers of early OA including cartilage glycoprotein-39(GP-39),matrix metalloproteinase-3(MMP-3),MMP-13,C-terminal telopeptide of type ? collagen(CTX?)and N-terminal telopeptide of type ? collagen(NTX?).Colorimetric fluorescence was used to measure the serum levels of citrate.UA levels in blood were measured using biochemical tests.Results 1.Associations between serum UA and knee symptoms,joint structural changes and biomarkers(1)Associations between serum UA and clinical characteristics in patients with knee OA: The serum UA level of the OA patients included in the study was within the normal range.Serum UA between different gender groups was statistically significant.There was no significant difference in the distribution of serum UA in different K-L grade groups and ROA,non-ROA groups respectively.(2)Associations between serum UA and joint symptoms of knee OA: Normal range serum UA was significantly and negatively associated with total WOMAC(?: 16.15,95% CI:-29.45,-2.85),joint pain(?:-3.15,95% CI:-6.11,-0.20),joint stiffness(?:-1.65,95% CI:-3.09,-0.21)after adjustment for age,sex and BMI through multivariable linear regression analysis.No significant association was observed between serum UA and dysfunction.(3)Associations between serum UA and structural change of knee OA: Normal range serum UA was positively associated with total cartilage volume,patella cartilage volume and medial tibia cartilage volume;however,the statistical significance disappeared after adjusting for confounding factors.There were no significant associations between serum UA and other structural change.(4)Associations between serum UA and biomarkers of knee OA: There was no statistically significant associations between normal range serum UA and biomarkers including GP-39,CTX?,NTX?,MMP-3 and MMP-13.2.Associations between serum citrate and knee symptoms,joint structural changes and biomarkers(1)Associations between serum citrate and clinical data in patients with knee OA: There was no significant difference in the distribution of serum citrate in different gender groups,different K-L grade groups and ROA,non-ROA groups,respectively.(2)Associations between serum citrate and joint symptoms of knee OA: No significant association was observed between serum citrate and WOMAC joint symptoms.(3)Associations between serum citrate and structural change of knee OA: Serum citrate was significantly and negatively associated with total OP grades(OR: 0.28,95% CI: 0.09,0.89),femur OP grades(OR: 0.30,95% CI: 0.09,0.99),total CD(OR: 0.29,95%CI: 0.09,0.90),medial femur CD(OR: 0.17,95% CI: 0.05,0.65),total BMLs(OR: 0.23,95% CI: 0.07,0.77)in multivariable analyses.No significant statistical association was observed between serum citrate and other structural change.(4)Associations between serum citrate and biomarkers of knee OA: Serum citrate was significantly and negatively associated with MMP-13(?:-310.64,95% CI:-619.81,-1.47).There was no significant associations between serum citrate and biomarkers including GP-39,CTX?,NTX? and MMP-3.Conclusions 1.In patients with knee OA,there was a significantly negative association between normal UA levels and the severity of joint symptoms including WOMAC total score,joint pain,and joint stiffness,suggesting that UA in normal range may play a protective role in OA symptoms.2.In patients with knee OA,there was a significantly negative association between serum citrate levels and changes in OA joint structures including OP formation,CD,and total BMLs,suggesting that serum citrate may have a protective effect in knee OA.3.In patients with knee OA,the level of citrate was significantly and negatively associated with serum MMP-13,a biomarker of cartilage metabolism in OA,suggesting that serum citrate may be involved in the cartilage metabolic mechanism of OA.Further research is needed to confirm these findings. |
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