Effect Of Different Therapeutic Targets On The RANKL/RANK/OPG System In Rheumatoid Arthritis

[Background]Rheumatoid arthritis(RA)is characterized by inflammation of the synovial tissues and the formation of “pannus” tissue that lead to destruction of both cartilage and bone matrix.The RANKL/RANK/OPG system is thougt to play a key role in this pathological process.The interaction among RANKL,RANK,and OPG affects the balance between osteoclasts and osteoblasts of RA,which in turn affects bone metabolism.And the role of the RANKL/RANK/OPG system in RA is now becoming a hot spot for the prevention and treatment of RA.[Object]To assess the efficacy and differences of Iguratimod combined with Methotrexate and Adalimumab combined with Methotrexate on the RANKL/RANK/OPG system in patients with RA,and to reveal the mechanism of different therapies on the destruction of cartilage and bone in RA.[Method]We chose 33 patients diagnosised as Rheumatoid arthritis and 13 healthy volunteers with age and gender matching,who were admitted to the inpatient department or outpatient department of the Second Affiliated Hospital of Guangzhou Medical University within September 2017 to September 2018.Patients diagnosised as RA were randomly divided into two groups,20 patients of which were treated with oral Iguratimod combined with MTX,and 13 patients of which were treated with Adalimumab subcutaneously and MTX orally.Ten healthy volunteers received no treatment and served as a healthy control group.RANKL and OPG concentrations in peripheral blood were detected by ELISA at 0 and 24 weeks in RA patients.Meanwhile,the swelling and pain of limb joints were evaluated.And the level of RF,ESR,and CRP were detected.[Results]1.Compared with the healthy control group,the serum RANKL and OPG concentrations of RA patients were higher than those of the healthy group,but the OPG/RANKL ratio was lower than that of the healthy group(P<0.05).2.Serum RANKL level(971.61 374.71pg/ml VS 668.77 295.94 pg/ml,t=4.202,p=0.001)decreased,OPG level decreased(3777.50 ±749.54 pg/ml VS 3268.14 ±712.89 pg/ml,p=0.011),and OPG/RANKL ratio increased(4.51 ±2.11 VS 5.77 ±2.75,p =0.015)after 24 weeks’ treatment of Iguratimod combined with MTX.3.Serum RANKL level(866.05 ±312.10 pg/ml vs 635.24 ±187.37pg/ml,p=0.018)and the serum OPG level(3839.69±701.31 pg/ml vs.3109.08 ±1131.27 pg/ml,p=0.039)decreased after 24 weeks’ treatment of Adalimumab combined with MTX,but there was no difference when compared OPG/RANKL ratio(p>0.05).4.There was no significant difference in the levels of RANKL,OPG and OPG/RANKL ratio between the Iguratimod group and the Adalimumab group(p>0.05).5.There was no correlation between the concentration of RANKL、OPG in peripheral blood and disease activity indexes in baseline RA patients [Conclusions]The concentration of RANKL and OPG in peripheral blood of RA patients was higher than that of normal people,but the ratio of OPG/RANKL was lower in the healthy group.Both alamod combined with MTX and adamzumab combined with MTX can reduce RANKL and OPG in peripheral blood of RA patients,suggesting that it has bone protection effect.There was no correlation between the concentration of RANKL and OPG in peripheral blood and disease activity indexes in baseline RA patients.