| Background Osteoarthriti（sOA）and obesity are common and chronic diseases in theworld and shows a progressively increasing incidence in the worldwide due to bothpopulation aging and to rising rate of metabolic syndromes, particularly obesity. Kneeosteoarthritis is one of the most common OA.Thepathogenesis of OA is not completelyunderstood.Currently,Foreign reports says that obesity as an ‘Chronic inflammatorystate’ plays a crucial role in osteoarthritis[1]. Adipocytokines promoted the productionof certain pro-inflammation cytokines,and may directly or indirectly throughpro-inflammation cytokines taking part in the pathogenesis of obesity-associated kneeOA.Leptin（LPT）,adiponectin（ADP）,resistin（RST）,interleukin-6（IL-6）,interleukin-17（IL-17） and interleukin-23（IL-23） are proinflammatory cytokines which are all made moreresearch in pathogenesis of osteoarthritis in recent years and play an important role inknee OA,but we can’t find any report in domestic about the the role of these adipokinesand pro-inflammatory cytokines to bone mineral density and to knee joint structure inobesity-associated osteoarthritis.Objective To determine the serum levels of LPT/ADP/RST and relatedpro-inflammatory cytokines IL-17/IL-6/IL-23in knee OA and analyze the relationshipwith duration length,sex,body mass index,anthropometrics,Clinical Data and LaboratoryIndicators,ect, in order to discuss the function and clinical significance of adipokinesand pro-inflammatory cytokines in knee OA;To describe the associations betweencytokines,bone mineral density and knee X-ray assessment in knee OA and their role inknee OA pathogenesis. Methods87knee OA patients was collected in the Rheumatology and ImmuneDepartment of the First Affiliated Hospital of Anhui Medical University during Januaryin the year of2012to August in the year of2012, including male8cases （9.1%）,7female9cases （90.8%）, female: male=9.8:1. Age was from38to74years old, and theaverage age was55.74±8.63years old. Duration of knee OA was from0.50to30years,and the average4（2,6.5）years. All the clinical and laboratory factors of knee OA wererecorded in details, such as height, weight, waist, The Western Ontario and McMasterors University Osteoarthritis Index （WOMAC）, Lequesne assessment of knee,erythrocyte sedimentation rate（ESR）,C reactive protein（CRP）, ect; Enzyme linkedimmunosorbent assay （ELISA） was used to examine the serum levels of LPT/ADP/RSTand related cytokine IL-17/IL-6/IL-23of experimental subjects of knee OA patients.BMD of the whole body, pelvis, lumbar spine1-4(L1-4),femur（femur neck, Ward area,greater trochanter） and body fat mass; Knee X-ray assessment containKellgren-Lawrence （K-L） grades, Osteophyte （OP） grades and joint-spacenarrowing（JSN） grades. Meanwhile knee OA patients were divided into groupsaccording to body mass index（BMI）, bone mineral density（BMD）, and knee X-rayassessment grades. Analysis the levels of serum LPT/ADP/RST, IL-17/IL-6/IL-23ofknee OA patients and the relationship with the clinical data,BMD, knee X-rayassessment.Results1. Adipocytokines and proinflammatory cytokines: Serum levels of LPT, IL-6infemale were obviously higher than male,and the comparison beween genderdifference was statistically significant（p<0.05）; Negative correlated was foundbeween serum ADP and IL-17.IL-23was positively associated with RST and also IL-6（p<0.05）.2. Adipocytokines, proinflammatory cytokines and clinical laboratory indexes:1) The relevance with clinical laboratory indexes: Positive correlation wasdetected between serum leption levels and the following: sex,waist hip ratio,BMI, body fat percentage （BF%）, total cholesterol （TC）, low densitylipoprotein （LDL）, the whole body fat mass, trunk fat mass of the patients withOA（both P<0.05）;Negative correlation was found between serum ADP andtotal glycerin（TG）, very low density lipoprotein（VLDL）（P<0.05）,andpositive correlation with high density lipoprotein（HDL）（p<0.05）; Negativecorrelation was found between serum IL-6and sex, BF%, TG（p<0.05）; Positivecorrelation was detected between serum IL-23and VLDL（p<0.05）.Nosignificant associations were found beween cytokines and age, duration length,WOMAC, Lequesne assessment.2) Comparsion with BMI groups: Serum LPT in normal weight group,overweight group and fat group of knee OA patients were9.29（3.35,10.54）、8.77（6.56,12.01）、16.01（10.90,31.07）ng/ml. Analysis of variance show thatthere were significant differences between them（x2=12.545，p=0.002）; Nosignificant differences were found about other cytokines in BMI groups.3) Influencing factors to cytokines: Linear regression show BF%, CRP, TC andage were influencing factors of serum LPT levels; HDL was the mostimportant influencing factors of serum ADP; WOMAC, Lequesne obviouslyinfluenced on serum RST;sex and waist hip ratio were important influencingfactors of serum IL-6;VLDL and physical function of WOMAC wasrespectively influencing factors of IL-17and IL-23. 3. Adipocytokines, proinflammatory cytokines and BMD:1) Negative correlation was found between serum LPT and the whole body BMD（P<0.05）. Negative correlation was detected between serum ADP and BMD of thebody as the following: the whole body, spine, pelvis, lumbar spine1-4(L1-4),femur（femur neck,Ward area） of the patients wit h OA（bothP<0.05）,among them spine, lumbar spine2-4（L2-4） were obviously correlated withserum ADP.Serum RST was negatively correlated with lumbar spine1（L1）. Thewhole body BMD and pelvis BMD were positively correlated with serum IL-6（P<0.05）.No statistical significance was found beween BMD and IL-17or IL-23.2) Comparsion with BMD groups: Serum LPT and ADP levels in normal BMD group,osteopenia group and osteoporosis group were gradually increased. Serum LPTlevels in osteoporosis group were obviously higher than that in normal BMD group{16.90（6.75,30.00） VS9.60（5.00,12.19），p<0.05}, and the same as Serum ADP{89.37（46.94,101.85） VS46.85（23.94,71.80），P＜0.01}.3) Influencing factors to BMD: Linear regression show serum ADP was independentand negative predictors of BMD at the whole body, spine, pelvis, lumbar spine1-4(L1-4), femur neck（both P<0.05）. Serum LPT was independent predictors ofBMD at the whole body. SerumIL-6was independent predictors of BMD at thespine, lumbar spine1-4(L1-4)（both P<0.05）.4. Adipocytokines, proinflammatory cytokines and knee X-ray K-L grades:1) BF%in K-L3grade was obviously higher than that in K-L2grade（39.83±4.01VS36.39±5.85，p＜0.05）, and waist hip ratio in K-L4grade was obviously higher thanthat in K-L2grade（0.96±0.04VS0.89±0.06，p＜0.05）, but no statisticalsignificance was found about other obesity-associated measure parameters in K-Lgrades, such as BMI, the total body fat mass or trunk fat mass.No statistical significance was found about the cytokines in K-L grades groups.2) The relationship with knee X-ray JSN grades: Ordinal Logistic analysis showedserum LPT was influencing factor of left knee medial tibiofemoral JSN （P<0.05）.Serum IL-6was influencing factor of left and right knee medial tibiofemoral JSN（both P<0.05）.Furthermore, Binary Logistic analysis showed serum IL-6was riskfactors for tibiofemoral JSN （OR>1，p=0.043）.3) The relationship with knee X-ray OP grades: Ordinal Logistic analysis showedserum RST, IL-6, IL-23were influencing factor of right knee medial tibiofemoralOP （P<0.05）.SerumIL-17was influencing factor of right knee medial tibiofemoralOP （P<0.05）. Furthermore, Binary Logistic analysis showed serum RST was riskfactors for left and right knee medial tibiofemoral OP（OR＜1，p=0.004）.Conclusion1. Obesity, gender was closely associated with knee OA. Adipocytokines andproinflammatory cytokines had close relationship in knee OA patients, and paly animportant role in the pathogenesis of knee OA. Adipocytokines, proinflammatorycytokines had close relationship with blood lipid and obesity indexes.2. Serum LPT and ADP maybe have adverse effect to bone mineral density of kneeOA patients.3. Obesity was a risk factor of knee OA, and increased knee joint structure damage.4. Serum LPT and IL-6was risk factors for medial tibiofemoral JSN. Serum RSTappeared to protective factors to medial tibiofemoral OP. |
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