Associations Between Gastrointestinal Peptide Hormones And Adipocytokines With Joint Symptoms,Structures And Bone Mineral Density In Patients With Knee Osteoarthritis

Backgrounds Osteoarthritis(OA)is the most common form of joint disease characterized by cartilage loss and osteophyte formation,and is the leading cause of joint pain and physical disability,which causes a large socioeconomic healthcare burden.Obesity is a wellrecognized risk factor,especially in weight-bearing joints.However,this relationship does not explain the incidence of OA in non-weight-bearing joint,such as hand OA and shoulder OA.Recent studies suggested thatmetabolic factors caused by obesity may play an important role in the pathogenesis of OA.Adipose tissue can secrete a series of adipocytokines,such as leptin,adiponectin,resistin,and visfatin.These adipocytokines may be important metabolic links that mediate OA production in obesity.Patients with OA often co-exist with osteoporosis(OP).Bone mineral density(BMD)is the best quantitative index to evaluate bone mineral content and diagnose OP.Many studies have explored the associations between OA and OP,but the effect of BMD on OA is still controversial.Our previous studies found that adiponectin may play a protective role in the progression of OA,while leptin and resistin may play a damaging role,and BMD may play a protective role in OA.The associations between adipocytokines and BMD in knee OA is rarely studied.Gastrointestinal tract is the largest endocrine organ of human body,which can secrete various peptide hormones,such as ghrelin,apelin,Vasoactive intestinal pe ptide(VIP),and Substance P(SP),which can participate in diet,obesity regulation,immune and inflammatory response.In recent years,it has been reported that gastrointestinal peptide hormones regulate bone and cartilage metabolism and ma y play a role in the occurrence of OA and OP.But there are few and controver sial related studies.Objectives 1.To examine cross-sectional associations of gastrointestinal peptide hormones with knee symptoms,joint structures and cartilage or bone biomarkers in patients with knee OA.2.To examine cross-sectional associations of gastrointestinal peptide hormones with bone mineral density in patients with knee OA.3.To investigate the cross-sectional associations between serum levels of adipokines and BMD in patients with knee OA.Methods This study included symptomatic knee OA.Serum levels of gastrointestinal peptide hormones including ghrelin,apelin,vasoactive intestinal peptide(VIP)and supstance P(SP),cartilage or bone biomarkers including cartilage oligomeric matrix protein(COMP),cross linked C-telopeptide of type I collagen(CTXI),cross linked N-telopeptide of type I collagen(NTXI),N-terminal procollagen III propeptide(PIIINP),and matrix metalloproteinase(MMP)-3,10,13,adipokines including leptin,adiponectin and resistin were measured using ELISA.Knee symptoms were assessed using the Western Ontario and Mc Master Universities Arthritis Index(WOMAC).Infrapatellar fat pad(IPFP)volume,IPFP signal intensity alternation,and cartilage defects were assessed using the magnetic resonance imaging.Osteophytes and joint space narrowing(JSN)were assessed using the Osteoarthritis Research Society International atlas.BMD of the total body,spine,hip and total femur,including femoral neck,Wards triangle,greater trochanter,and femoral shaft were measured using dual-energy x-ray absorptiometry(DXA).Results 1.The associations between gastrointestinal peptide hormones and knee symptoms,joint structures and biomarkers in patients with knee OA.(1)Quartiles of ghrelin were positively associated with knee symptoms including pain,stiffness and dysfunction.Quartiles of ghrelin were also significantly associated with increased IPFP signal intensity alteration and quartiles of NTXI,PIIINP,MMP-3 and MMP-13.Ghrelin was not significantly associated with other joint structures and biomarkers.(2)Quartiles of apelin were negatively associated with OA symptoms of pain,patellar femroaltibial joint bone marrow lesions and serum levels of MMP-13,and were positively associated with serum levels of CTXI.(3)Quartiles of VIP were negatively associated with lateral femoral joint bone marrow lesions,and were positively associated with serum levels of MMP-13.(4)Quartiles of SP were negatively associated with serum levels of MMP-13.SP was not significantly associated with joint and symptoms and joint structures.2.The associations between gastrointestinal peptide hormones and BMD in patients with knee OA.Quartiles of apelin were negatively associated with BMD at spine and hip.Quartiles of VIP were positively associated with BMD at total femur,femoral shaft and greater trochanter in osteoporosis group,and were negatively associated with BMD at wards triangle in normal bone mass group and reduced bone mass group,and femoral neck in normal bone mass group.Quartiles of SP were positively associated with BMD at totoal body in osteoporosis group,and were negatively associated with BMD at total body,spine and hip in normal bone mass group.No significant associations were found between serum ghrelin and BMD at any site measured.3.The associations between serum levels of adipokines and BMD in patients with knee OA.Serum levels of leptin were significantly associated with reduced BMD at total body,hip,total femur,femoral neck,and femoral shaft.Serum levels of adiponectin were significantly and negatively associated with BMD at total femur and femoral shaft.However,no significant associations were found between serum levels of resistin and BMD at any site measured.Conclusions 1.Serum levels of ghrelin were significantly associated with increased knee symptoms,IPFP signal intensity alteration and serum levels of MMP-3,MMP-13,PIIINP and NTXI.Serum levels of apelin were significantly negatively with knee pain,patellar bone marrow lesions,and serum levels of MMP-13,and positively associated with serum levels of CTXI.Serum levels of VIP were significantly negatively with lateral femoral bone marrow lesions and positively associated with serum levels of MMP-13.These findings suggested that gastrointestinal peptide hormones may have a role to play in knee OA.2.Serum levels of apelin were significantly and negatively associated with BMD,suggesting potentially detrimental effects of apelin on BMD in knee OA patients.Serum levels of VIP and SP were significantly and positively associated with BMD in osteoporosis group,and were negatively associated with BMD in normal bone mass group and reduced bone mass group,suggesting potentially protective effects of VIP and SP on BMD in osteoporosis and detrimental effects in non-osteoporosis.3.Serum levels of leptin and adiponectin were significantly and negatively associated with BMD,suggesting potentially detrimental effects of leptin and adiponectin on BMD in knee OA patients.