Change Of OPG/RANKL System In Patients With Rheumatoid Arthritis And Study Of Relationship Between OPG/RANKL With Osteoporosis

BackgroundRheumatoid arthritis(RA) is a common disease which synovitis is the major pathology feature. It is a chornic autoallergic disease which can lead destruction of articular cartilage and bone. Destruction of articular cartilage and bone are the primary cause of descending of quality of life and deformity. Along with the penetrating of investigation for the past few years, some research about osteoclaste and its regulatory factor show osteoclaste is the important cell of destruction of articular and bone in RA. Changes of function of osteoclaste and osteoclastogenesis inhibitory factor and osteoclast differentiation factor play an important role in osteoporosis and bone erosion of RA. Interaction of OPG/RANKL/RANK system and T cell can partly explain this damage of joint and bone. Current study show OPG and RANKL are key regulatory factors in RA. So study of change of OPG and RANKL in RA have actually significance for understanding the osteoporosis and bone invasion in RA. It probably provide foundational research data for the further therapy of prevention of bone invasion in the future.ObjectivesTo determine the level of OPG and RANKL in peripheral blood and synovial fluid of RA and normal controls, determine the bone mineral density of all patients with RA and normal controls. Investigating the change of OPG/RANKL system in patients with RA and the relationship between OPG/RANKL with osteoporosis.MethodsA total of 64 patients with RA who were diagnosed as having RA as defined by the American College of Rheumatology 1987 revised criteria were involved. Collecting blood samples of all the patients and 60 normal controls whose age and sex were matched to RA. Synovial fluid were also collected from 21 patients who had arthroedema in knee joint. Level of OPG and RANKL were measured by ELISA. BMD of non-dominant forearm, lumbar vertebrae(L1-4) and hip were measured by dual energy X-ray absorptiometry. The clinical and laboratory measurements were done simultaneously. Comparasion of level of OPG and RANKL between RA and normal controls, comparasion of level of OPG and RANKL in RA between sera and synovial fluid were conducted. Correlations between change of OPG/RANKL system in RA and BMD, osteoporosis were analyzed.Results1. Compared with normal controls, the level of OPG and OPG/RANKL in RA decreased significantly, the level of RANKL in RA increased significantly(P<0.0001). The level of OPG and RANKL in RA synovial fluid were higher than that in RA peripheral blood(P<0.0001). There was no difference of OPG/RANKL in RA between peripheral blood and synovial fluid(P>0.05).2. BMD of all detected region such as non-dominant forearm, lumbar vertebrae(L2-4) and hip in RA were significant reduced than that in normal controls(P<0.0001). There was a higher incidence of osteoporosis in patients with RA(35.9%) than that in normal controls(15.0%)(P<0.0001). 3. The level of peripheral blood OPG, RANKL and OPG/RANKL were significant difference between RA and normal controls under different bone metabolism status(P<0.0001). The worser of bone metabolism status, the lower of OPG, the higher of RANKL in peripheral blood of RA. Index of joint swollen and tenderness in RA were obviously different among different bone metabolism status(P<0.05-0.01).4. Either under status of normal bone mass, or osteopenia, or osteoporosis, the level of OPG and OPG/RANKL in RA were obviously lower than that in normal controls (P<0.0001), the level of RANKL in RA was obviously higher than that in normal controls(P<0.0001). BMD of most region in RA were obviously lower than that in normal controls(P<0.0001), especially under status of osteoporosis.5. Both in RA and in normal controls, the level of OPG, RANKL and OPG/RANKL were same in different sex groups. Either in RA or in normal controls, compared with premenopause women, the level of OPG decreased significantly in menopause women(P<0.0001), the level of RANKL increased significantly in menopause women(P<0.0001). BMD of menopause women in RA were obviously lower than that of premenopause women(P<0.0001). There were no difference in BMD, incidence of osteoporosis, peripheral blood OPG, RANKL, OPG/RANKL between patients with RA who ever used glucocorticoid or not(P<0.0001).6. There was a negative line correlation between age and level of OPG of peripheral blood in RA(P<0.0001). There were positive line correlation between BMD and level of OPG of peripheral blood in RA(P<0.05-0.001). There was a positive line correlation between age and level of RANKL of peripheral blood in RA(P<0.0001). There were negative line correlation between BMD and level of RANKL of peripheral blood in RA(P<0.05-0.001). There were positive line correlation between index of joint swollen and tenderness, HAQ, BPC and level of OPG/RANKL of peripheral blood in RA(P<0.05-0.001). There was a positive line correlation between BMD of L3 only and level of OPG/RANKL of peripheral blood in RA(P<0.026).7. Analysis of Logistic Regression showed the level of RANKL in peripheral blood in RA was a independent, intensive risk factor in occurrence of osteoporosis of RA (OR=126.42, CI 95%: 37.87-185.36).Conclusion1. Compared with normal controls, the level of OPG and OPG/RANKL in RA decreased significantly, the level of RANKL in RA increased significantly. There was a higher incidence of osteoporosis in patients with RA than that in normal controls. The worser of bone metabolism status, the lower of OPG, the higher of RANKL in peripheral blood of RA.2. There were closely correlation between age, menopause and BMD, the level of OPG, RANKL. There were closely correlation between the level of OPG/RANKL and joint swollen and tenderness, HAQ, BPC.3. Increasing of RANKL in peripheral blood in RA was a independent, intensive risk factor in occurrence of osteoporosis of RA.