The Associations Between Serum Biomarkers,Diet Intake And Knee Osteoarthritis

Objectives: At present,the diagnosis and monitoring of osteoarthritis(OA)mainly depends on clinical symptoms,radiological assessment and traditional laboratory examinations.However,these methods can not identify the early stage of OA.Finding method which can diagnosing OA in early stage can help control the progress of OA.Biomarkers can diagnose OA simply and conveniently in the early stage,and are considered as a promising diagnostic tool for OA.Therefore,the first part of this study is to investigate the associations between serum matrix metalloproteinase 13(MMP13),interleukin-8(IL-8)and S100A8/S100A9 and knee structure and symptoms in knee OA patients,so as to provide clues for the selection of serum biomarkers and targeted therapy of knee OA.Currently,the treatment of OA is limited.More and more evidences showed that diet plays a role in the occurrence and development of OA,modern diet has a harmful effect on OA,adjusting diet could be a safe and effective way to control OA.Therefore,the second part of this study is to explore the role of dietary factors in knee OA by studying the effects of Australian Recommended Food Score(ARFS),dietary intake of energy and nutrients,and dietary macronutrients and micronutrients on joint structure,knee OA related symptoms,and serum adipokines and inflammatory cytokines in knee OA patients.Methods: The data of this study come from two databases.The first database is the Anhui Osteoarthritis(AHOA)study.This database contains 205 patients with symptomatic knee OA.Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)and Lequesne index were used to evaluate joint symptoms in patients with knee OA.Radiography was used to evaluate Kellgren-Lawrence(K-L)grade,joint space narrowing and osteophyte.Magnetic resonance imaging(MRI)wasused to measure cartilage volume,cartilage defect,subchondral bone marrow lesion(BML),effusion synovitis area,infrapatellar fat pad(IPFP)volume and IPFP signal intensity alteration.Enzyme linked immunosorbent assay(ELISA)was used to measure serum levels of MMP13,IL-8 and S100A8/S100A9.The associations between serum MMP13,IL-8,and S100A8/S100A9 and knee structure and symptoms in patients with knee OA were analyzed by linear regression or ordinal regression model.The second database is the Vitamin D Effect on Osteoarthritis(VIDEO)study.This database contains 413 patients with symptomatic knee OA.Dietary Questionnaire for Epidemiological Studies Version 2(DQES v2)was used to investigate dietary status of the patients.Based on DQES v2,ARFS was calculated.WOMAC and knee pain Visual Analogue Scale(VAS)were used to evaluate knee symptoms of patients;dynamometry at the lower limb was used to measure lower limb muscle strength of patients;Assessment of Quality of Life(AQoL)was used to evaluate the quality of life of patients;Manchester Foot Pain and Disability Index(MFPDI)was used to evaluate foot pain and function of patients;questionnaires including Chronic Pain Grade Questionnaire(CPGQ),Back Beliefs Questionnaire(BBQ)and so on were used to evaluate lower back pain of patients,and Patient Health Questionnaire-9(PHQ-9)was used to evaluate depression symptoms of patients.MRI was used to measure cartilage volume,cartilage defect,subchondral BML and effusion synovitis volume.ELISA was used to measure serum levels of leptin,adiponectin,resistin,adipsin,and apelin.Bio-plex Luminex kit was used to measure serum levels of granulocyte-macrophage colony stimulating factor(GM-CSF),IL-1 ?,IL-2,IL-4,IL-6,IL-8,IL-10,IL-12,IL-17 A,IL-17 F,IL-21,IL-22,and IL-23.Linear mixed-effects model was used to analyze the effects of baseline ARFS,dietary intake of energy and nutrients,and dietary macronutrients and micronutrients on changes of joint structure,knee OA related symptoms,and serum adipokines and inflammatory cytokines in knee OA patients over 2 years.Results: In the first part of this study with patients of symptomatic knee OA,serumMMP13 was positively associated with K-L grade,knee cartilage defect and IPFP signal intensity alteration,negatively associated with knee cartilage volume and IPFP volume;serum IL-8 was positively associated with knee symptoms and IPFP signal intensity alteration,besides,in patients with knee radiographic OA,serum IL-8 was positively associated with K-L grade;serum S100A8/S100A9 was positively associated with knee symptoms and cartilage defect.In the second part of this study with patients of symptomatic knee OA,total score of ARFS and its vegetable score were widely associated with amelioration of knee symptoms,lower limb muscle strength,quality of life,foot pain and function,lower back pain and depressive symptoms,scores of other ARFS subtypes,such as ARFS fruit and ARFS grains,were also associated with amelioration of some knee OA related symptoms;total score of ARFS was associated with decrease of some adipokines and inflammatory cytokines,score of ARFS vegetables was associated with decrease of some inflammatory cytokines,scores of ARFS fruits,ARFS grains,ARFS dairy and ARFS fats were also associated with decrease of some cytokines.In patients with symptomatic knee OA,intake of protein and fibre were associated with amelioration of knee joint structure;intake of energy was associated with deterioration of quality of life,lower back dysfunction and depressive symptoms;intake of total fat was associated with deterioration of knee symptoms and quality of life;intake of saturated fat was associated with deterioration of knee symptoms,lower limb muscle strength,quality of life and depressive symptoms;intake of starch was associated with amelioration of knee symptoms;intake of fibre was associated with amelioration of knee symptoms,lower limb muscle strength,quality of life,lower back pain intensity and depression symptoms;intake of energy,total fat,saturated fat and monounsaturated fat was associated with increased inflammatory cytokines and/or adipokines;intake of carbohydrates and starch were associated with decreased adipokines,and increased inflammatory cytokines,intake of fibre was associated with decreased adipokine leptin.In patients with symptomatic knee OA,intake of calcium,potassium and zinc were associated with amelioration of knee structure,intake of sodium was associatedwith deterioration of patellar knee structure,and amelioration of tibial and femoral knee structure;intake of calcium was associated with amelioration of knee pain,independent living ability,lower back pain intensity,and fear and misperception of lower back pain;intake of magnesium was associated with amelioration of knee function,lower limb muscle strength,quality of life,foot related function,lower back pain,fear and misperception of lower back pain,and depressive symptoms;intake of phosphorus was associated with amelioration of knee symptoms,lower limb muscle strength,quality of life,foot related function,fear and misperception of lower back pain,and depressive symptoms;intake of potassium was associated with amelioration of knee symptoms,lower limb muscle strength,quality of life,foot pain and function,and fear and misperception of lower back pain,and depressive symptoms;intake of iron was associated with amelioration of knee symptoms;intake of sodium intake was associated with deterioration of mental health;intake of calcium,magnesium,phosphorus and potassium were associated with decrease of leptin,besides,intake of potassium was also associated with decrease of apelin.Conclusions: In patients with symptomatic knee OA,serum MMP13 is associated with knee structural injury,serum IL-8 and S100A8/S100A9 are associated with knee structural injury and more serious knee symptoms,suggested that MMP13,IL-8 and S100A8/S100A9 may be involved in the pathogenesis of knee OA,and could be biomarkers of knee OA.In patients with symptomatic knee OA,high quality diet such as adequate vegetable intake has a widely protective effect on knee OA related symptoms.Dietary intake of energy and fat have damaging effect in knee OA,while intake of starch and fibre have protective effect in knee OA.Dietary intake of calcium,magnesium,phosphorus,potassium and iron have protective effects on knee OA.The effects of the above dietary factors on knee OA may related to their regulation on metabolism and inflammation.