1.Clinical study of osteoporotic fracture in patients with rheumatoid arthritis
Tong LIU ; Shengqian XU ; Juan DENG ; Biwei PEI ; Chen CHEN ; Jianhua XU
Chinese Journal of Rheumatology 2013;(5):341-345
Objective To investigate the clinical features and related risk factors of osteoporosis (OP) and osteoporotic fracture (OPF) in patients with rheumatoid arthritis (RA).Methods Two hundred and seventytwo in-patients with RA between 2010-2011 were surveyed,X-ray was detected for the diagnosis of fracture.Bone mineral density(BMD) of proximal femur and lumbar vertebrae (L2-4) in 203 patients were measured by dual energy X-ray absorptio-metry (DEXA),and the radiographic changes in both hands of 169 RA patients were assessed by Sharp scoring system.All the clinical and laboratory factors of RA were recorded in detail by rheumatologists.The results of 120 normal people were used as controls.T-test,Mann-whitney test,x2 test and Logistic regression were used for statistical analysis.Results ① Compared to the normal group,the BMDs of RA patients at each measured location were significantly lower (P<0.01),the OP incidence was 32.0% (65/203),which was significantly higher than that of the normal group,which was 15.0% (18/120) (x2=11.442,P=0.001).There were 33 cases of OPF among all 272 RA patients,and the occurrence rate was 12.1%.BMDs of the femur in RA with OPF were lower than those in RA without OPF (P<0.01).② Incidence of OP in RA with glucoco-rticoid was 42.2%(46/109),which was higher than that in RA without glucocorticoid (20.2%,18/89) (x2=10.818,P=0.001).Compared with RA without glucocorticoid,the incidence of OPF in RA with glucocorticoid elevated evidently [7.2% (9/125) vs 17.5% (24/137)] (x2=6.321,P=0.012).③ Logistic regression (back-ward LR method) analysis found that the risk factors for OP in RA patients were age [OR=1.050,P=0.001,95%CI(1.020,1.080)],HAQ [OR=1.966,P=0.031,95%CI (1.064,3.631)],and glucocorticoid average daily dosage [OR=1.075,P=0.031,95%CI (1.007,1.148)].The risk factors for OPF in RA patients were age [OR=1.041,P=0.046,95%CI (1.001,1.084)] and OP [OR=3.484,P=0.016,95%CI (1.258,9.646)].Conclusion RA patients have higher incidence of OP and OPF than general population.The incidence of OP and OPF are closely correlated with age,diseases activity,local bone erosion and the use of glucocorticosteroid.
2.Association of tumor necrosis factor-α receptor gene single nucleotide polymorphism in patients with ankylosing spondylitis
Chen CHEN ; Biwei PEI ; Shengqian XU ; Juan DENG ; Tong LIU ; Faming PAN ; Jianhua XU
Chinese Journal of Rheumatology 2013;(1):31-36
Objective To investigate the value of tumor necrosis factor (TNF)-α receptor gene,TNFRSF1A+36A/G(rs767455) and-383A/C(rs2234649),TNFRSF1B+196T/G(rs1061622) single nucleotide polymorphism (SNP) for the susceptibility to ankylosing spondylitis (AS) and the relationship between SNP and AS.T test,Chi-square test,and ANOVA were used for statististical analysis.Methods Two hundred and fifteen patients who had definite diagnosis of AS and 216 healthy blood donors were involved in this study.SNPs of TNF-α receptor gene:TNFRSF1A +36A/G(rs767455),-383A/C(rs2234649) and TNFRSF1B+196T/G (rs1061622) were detected with the ligase detection reaction (LDR-PCR) method.Results ① Distribution frequencies of A alleles(86.8%,91.5%) and G alleles (13.2%,8.5%) of TNFRSF1A(rs767455) in AS and controls were significantly different with each other (x2=4.627,P=0.0315),while the distribution frequency in group of homozygotes (AA or GG genotype) in AS and controls were 74.6%(150/201) and 83.9%(177/211),the frequencies in group of heterozygotes (AG) were 25.4% (51/201) and 16.1%(34/211)(x2=5.390,P=0.020).Frequency of alleles and the genotypes of TNFRSF1A (rs2234649) and TNFRSF1B (rs1061622) between AS and control group were similar(P>0.05).It also demonstrated that TNF-αreceptor gene haplotype (rs1061622T-rs2234649A-rs767455G) carriers apparently increased the susceptibility to AS (11.5% vs 6.9%)(OR:1.753,95%CI:1.078~2.852,P=0.022).② Analysis of variance found that the duration of morning stiffness (F=3.168,P=0.044) and peripheral joint tenderness counts (F=4.598,P=0.011) among the three genotype groups of TNFRSF1B (rs1061622) in patient with AS were evidently differed with each other.Bath AS functional index (BASFI) among different genotype groups of TNFRSF1A (rs2234649) in AS had remarkable diversity (F=5.783,P=0.004).None of above indicators among groups of different genotypes of TNFRSF1A (rs767455) in AS were uniform (P>0.05).③ Forty-four patients were treated with TNF-α antagonist (entanercept),25 mg,subcutaneous injection,twice weekly for 3 months,then followed with Sulfaslazine (SASP) 2.0 g/d and Celecoxib 0.4 g/d for another 9 months.ASAS20 was the primary endpoint for the evaluation of therapeutic effect at the visit of 3 month and 12 month.No associations were found between SNP and short or long term outcome of treatment with TNF-α antagonist in AS (P>0.05).Conclusion TNFRSF1A (rs767455) SNP correlates with susceptibility to AS in Anhui Han local patients.Carriers of TNF-α receptor gene haplotype (rs1061622T-rs2234649A-rs767455G) may increase the susceptibility to AS.SNP of TNFRSF1B (rs1061622) is associated with disease activity in AS,while SNP of TNFRSF1A(rs2234649)relates to functional index of the disease.There is no association between SNP of TNFRSF1A / TNFRSF1B and short or long term outcome of treatment with TNF-α antagonist in AS.
3.Association of general osteoporosis and local bone erosion in patients with rheumatoid arthritis
Juan DENG ; Biwei PEI ; Shengqian XU ; Tong LIU ; Chen CHEN ; Jianhua XU
Chinese Journal of Rheumatology 2012;16(10):674-678
Objective To investigate the relationship between the general osteoporosis and local bone erosion in patients with rheumatoid arthritis (RA).Methods Bone mineral density (BMD) of femur (femur neck,Ward area,greater trochanter) and lumbar spine 2-4 (L2-4) by dual energy X-ray absorptiometry was measured in 120 patients with RA and 120 normal controls.All the clinical and laboratory factors of RA were recorded in details,and the radiographic changes in both hands of 76 RA patients were assessed by Sharp'method.Statistical anylysis was carried out by using t test and x2 test.Results ① Compared with normal controls,the BMD of total femur,L2,L3,L4 and L2-4 decreased significantly (P<0.01),while there was no significant differences in the BMD of femur neck,Ward area and greater trochanter between the two groups (P>0.05).② The incidence of osteoporosis in RA (34.2%) was higher than that in normal controls (15.0%)(x2=11.889,P=0.001).③ Patients with osteoporosis had elder age,higher scores of HAQ,higher scores of space narrowing and bone erosion of joint by X-ray' Sharp method than those of patients without osteoporosis.There were no significant differences in the changes of other clinical and laboratory parameters between the two groups(P>0.05).④ BMD of total femur,femur neck,Ward area,greater trochanter,L2,L3,L4 correlated with Sharp scores in RA and had shown a negative correlations(P<0.05).Logistic regression analysis showed that age(OR=1.069,P=0.012,95%CI:1.015-1.125) and Sharp scores(OR=1.022,P=0.003,95%CI:1.007-1.037) were risk factors for osteoporosis in RA patients,but treating with DMARD (OR=0.172,P=0.041,95%CI:0.032-0.930) was a protective factor for osteoporosis in patients with RA.Conclusion The BMD decreases significantly and correlates with age and local bone erosion in patients with RA,while the incidence of osteoporsis increases remarkably.
4.The relationship between single-nucleotide polymorphism in RANKL, osteoprotegerin gene and rheumatoid arthritis
Biwei PEI ; Shengqian XU ; Tong LIU ; Juan DENG ; Xiaomeng SHEN ; Faming PAN ; Jianhua XU
Chinese Journal of Rheumatology 2012;16(11):732-737
Objective To investigate the relationship between single-nucleotide polymorphism (SNP)in receptor activator for nuclear factor-κB ligand (RANKL),osteoprotegerin (OPG) gene and rheumatoid arthritis (RA).Methods In our study,3 SNPs in the genes of OPG (2 SNP:rs2073618,rs3102735) and RANKL (1 SNP:rs2277438) by ligase detection reactions from 200 RA and 201 controls were examined.BMD values of different areas were assessed using dual-energy X-ray absorptiometry.Clinical and laboratory parameters were collected.Analysis of variance,t-test and x2 test were used for statistical analysis.Results No signi-ficant differences in the distribution of the alleles and genotypes were observed between case group and the control group (P>0.05).The haplotype analysis for RANKL and OPG SNPs showed that the rs2073618/rs2277438/rs3102735 GGG haplotype could reduce the risk of RA (1.5% vs 6.0%,P=0.008; OR 0.216;95%CI:0.081 to 0.575) and the GAG haplotype increased the risk of RA (14.5% vs 8.4%,P=0.007; OR 1.862,95%CI:1.179 to 2.943).Patients with RANKL-rs2277438 AA or GG genotypes (n=6) had significantly higher BMD values compared to those with AG genotypes (n=39) at spine lumber 3 (1.05±0.22 vs 0.93±0.26,t=2.314,P=0.023),spine lumber 4 (1.06±0.24 vs 0.94±0.28,t=2.27,P=0.030),spine lumber 2-4 (1.04±0.21 vs 0.89±0.28,t=2.788,P=0.007).The tender joint counts (13±7 vs 10±6),tender joint index (19±11 vs 13±9),and VAS score (5.7±1.9 vs 4.8±1.8) differed significantly between patients with the OPG-rs2073618 CC or GG genotypes (n=60) and GC genotypes (n=40).Conclusion The rs2073618/rs2277438/rs3102735GGG haplotype may be protective against RA,while GAG haplotype may increase the susceptibility to RA.RANKL gene SNP rs2277438 may affect BMD value at spine lumber,and OPG gene SNP rs2073618 may influence the disease activity of RA patients.