| BackgroundRheumatoid arthritis (RA) is a common disease which the characteristic pathologicalfeature is synovitis, eventually it can lead to local destruction of articularcartilage/bone and general bone loss. Bone and joint injuries are the predominantcause which results in reduced quality of life and disability in patients with RA. Localbone erosion and systemic bone loss are the manifestation of RA patients conceringbone and joint injuries, the systemic bone loss manifested as apparently reduce inbone mass and decline bone mineral density (BMD), which give rise to significantlyhigher incidence of osteoprosis (OP) in patients with RA. Occurence of OP is boundto increased risk of osteoporotic fractures (OPF) in RA patients, and to some extentmakes the increased mortality of patients with RA. Activating factor nuclear factorkappa B receptor ligand (RANKL)/nuclear factor kappa B receptor activation factor(RANK)/osteoprotegerin (OPG)(RANKL/RANK/OPG) system which plays animportant role on bone metabolism has been paied more and more attention recentyears. Researches found RANKL/RANK/OPG system can partly explain this damageof joint and bone in RA. RANKL/RANK/OPG system has been regarded as an vitallinkage between immune system and bone damage of RA，but rarely reported in RApatients with OPF.ObjectiveTo investigate the correlation between OPF occurrence in patients with RA andperipheral blood RANKL and OPG levels.MethodsOccurrence of OPF at all detected sites including hip, lumbar vertebra distal radius and so on in the past or recent in384patients with RA from2010to2012weresurveyed by cross sectional analysis method. All the clinical and laboratory factors ofRA were recorded in detail, especially the ones who accompanied with OPF. Plainradiology X-ray method were used for the evaluation of OPF, semiquantitative (SQ)method was especially utilized for the decision, type and degree of OPF at vertebra.The radiographic changes in both hands of all RA patients were assessed by Sharp’smethod. The level of RANKL and OPG in the peripheral blood of220RA patientsand100cases of normal person (according to2:1ratio, matched with age and gender)were detected by ELISA, BMD of femur (femur neck, Ward area, greater trochanter,total femur) and lumbar spine2-4(L2-4) by dual energy X-ray absorptiometry wasmeasured in327cases of patients with RA and158cases of normal controls.Results1.82cases of OPF, a rate of21.35%, occurred in all the384patients with RA.64cases with vertebral body fracture in RA are the largest group, which account for arate of16.67%,12th thoracic vertebra and1st lumbar vertebra were the mostpredominant sites.2. The peripheral blood levels of RANKL (150.13±143.04vs101.40±65.64，t=4.178，P<0.0001)、OPG (456.89±292.69vs358.94±216.10，t=3.347，P=0.001) and ratioof RANKL/OPG (0.41±0.35vs0.34±0.20， t=2.111， P=0.036) in RA weresignificantly higher than that in normal group.3. In comparison with normal controls, BMD of following detected regions includingfemur neck, Ward area, greater trochanter, total femur, L2, L3, L4and L2-4in RAdecreased obviously (P<0.01-0.0001). The incidence of osteoporosis in RA(121/327,37%) was higher than that in normal controls(22/158,13.92%)(x~2=27.291，P<0.001).4. RA with osteoporosis had elder age(59.48±12.81vs50.78±12.51，t=6.010，P<0.0001), lower BMI(20.81±3.49vs22.27±3.35，t=3.690，P<0.0001), longerduration of disease(11.34±9.61vs6.96±7.92，t=4.163，P<0.0001), higher HAQscore(1.72±0.63vs1.51±0.69,t=2.768,P=0.006),elevated erum AKP(107.56±88.75 vs90.25±38.48，t=2.147，P=0.033), higher joint space narrow score in handsX-ray(42.67±33.47vs20.43±25.06，t=5.949，P<0.0001), higher bone erosionscore in hands X-ray(43.14±35.59vs18.59±25.23，t=6.229，P<0.0001), higherSharp score in hands X-ray (85.81±67.89vs39.02±49.65，t=6.176，P<0.0001),worse constituent ratio of joint function (1:48:57:5vs16:100:68:3，x~2=14.536，P=0.002), worse constituent ratio of X-ray stage (10:17:39:45vs32:56:69:31，x~2=25.107，P<0.0001), higher rate of usage of glucocorticoid (69.6%(80/115) vs53.8%(106/197)，x~2=7.489，P=0.006). The other clinical and laboratory parameters(including peripheral RANKL and OPG level) between the two groups have noobvious difference (P>0.05).5. RA patients with OPF have higher age(59.91±11.29vs52.70±13.71，t=4.377，P<0.0001), longer duration of disease(11.01±8.88vs8.11±8.85， t=2.612，P=0.009), higher RANKL level(217.31±193.33vs124.12±108.72，t=3.554，P=0.001), higher RANKL/OPG ratio(0.54±0.52vs0.36±0.25，t=2.651，P=0.010),higher HAQ score(1.69±0.66vs1.48±0.70，t=2.418，P=0.016), lower serumcalcium level(2.20±0.16vs2.25±0.16，t=2.183，P=0.030), lower hemoglobinlevels(104.90±19.73vs109.99±19.63，t=2.125，P=0.036), higher joint spacenarrow score in hands X-ray(37.11±33.00vs26.13±29.42，t=2.552，P=0.012),higher bone erosion score in hands X-ray(37.79±34.75vs24.91±30.67，t=2.848，P=0.005)，higher Sharp score in hands X-ray(74.89±66.62vs51.03±59.32，t=2.747， P=0.007), worse constituent ratio of joint function(3:29:42:5vs18:146:96:8， x~2=11.115， P=0.011), worse X-ray stage(10:16:25:30vs39:66:102:57， x~2=7.856， P=0.049), higher glucocorticoid utilization rate(72.0%(59/82) vs53.3%(153/287)，x~2=9.066，P=0.003), higher incidence of OP(67.1%(51/76) vs28.0%(70/250)，x~2=38.186，P<0.0001)，compared with patientswithout OPF. While the other clinical and laboratory parameters between the twogroups have no apparent discrepancy (P>0.05).6. RA patients taking corticosteroids had worse joint function composition (5:94:94:9vs16:80:44:4， x~2=17.702， P=0.001), worse X-ray stage (18:38:80:63vs30:44:47:23，x~2=22.375，P<0.0001), and higher proportion of patients with severe disease activity (63.0%(121/192) vs50.4%(67/133)，x~2=5.152，P=0.023), higherincidence of OP (43.0%(80/186) vs27.8%(35/126)，x~2=7.489，P=0.006) and higherincidence of OPF (27.8%(59/212) vs14.6%(23/157)， x~2=9.066， P=0.003).Incidence of OP at the site of L2(28.5%(53/186) vs15.9%(20/126)，x~2=6.745，P=0.034) and L4(19.4%(36/186) vs11.1%(14/126)，x~2=13.387，P=0.001) in RApatients who took glucocorticoids were obviously higher than that in patients nottaking glucocorticoids, while the incidence of OP at other regions was similarbetween patients with and witout glucocorticoids (P>0.05).7. Peripheral OPG level in RA patients positively correlated with CRP (r=0.171,P=0.013), Serum RANKL level positively correlated with ESR(r=0.160, P=0.023).There was a positively linear correlation between RANKL/OPG ratio and age (r=0.136, P=0.044), while there were no correlations between the other clinical andlaboratory parameters (P>0.05).8. The binary classification Logistic Regression (Backward LR method) analysisshowed that age（OR=1.051， P=0.001，95%CI：1.022-1.081）, BM（IOR=0.863，P=0.006，95%CI：0.777-0.958） and Sharp score（OR=1.013，P<0.0001，95%CI：1.007-1.019） are risk factors for RA patients with OP. Age（OR=1.029，P=0.039，95%CI：1.001-1.057）and the occurrence of OP（OR=3.159，P=0.001，95%CI：1.562-6.385）, RANKL/OPG ratio（OR=3.516，P=0.013，95%CI：1.305-9.647） are risk factors for RA patients with OPF.Conclusion1. OP is prevalent in RA, which the incidence is the2.65times as high as that innormal. A higher incidence of OPF (21.35%) is also seen in RA，vertebra is thepredominant site for OPF.2. The peripheral blood levels of RANKL, OPG and ratio of RANKL/OPG in RAwhich correlates with disease activity of RA, were significantly higher than that innormal group.3. Occurrence of OPF in RA is associated with age, duration of disease and status of disease. It also correlates with RANKL/OPG system and the usage ofglucocorticoid. Age, the occurrence of OP, RANKL/OPG ratio are risk factors forRA patients with OPF. |
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