Study On Bone Mineral Density, Bone Metabolism And Related Factors In Patients With Connective Tissue Disease

1.Changes in bone mineral density,bone metabolism index and influencing factors in patients with connective tissue disease ObjectiveConnective tissue disease(CTD)is a type of disease that can affect multiple systems and organs throughout the body.Clinically,CTD patients have more or less the occurrence of bone mass changes.Clinical studies have found that patients with CTD can have different degrees of bone loss,and the risk of fracture is much higher than that of ordinary people.Therefore,this study systematically understands the changes in bone mass in patients with CTD by measuring bone mineral density and bone metabolism in patients with CTD,and identifies the risk factors affecting bone mass changes through correlation analysis.Further explore the role of bone metabolism markers in bone mass changes in patients with CTD,and provide a theoretical basis for assessing bone mass abnormalities in patients with CTD.Methods(1)240 patients with CTD were selected,including 63 patients with SLE,123 patients with RA,and 54 patients with pSS.70 healthy volunteers.According to the disease type,it was divided into the overall CTD group,SLE group,RA group and pSS group.According to the bone density,it was divided into normal bone mass group,bone mass reduction group and osteoporosis group.There was no statistically significant difference in age and sex ratio between the total CTD group and the healthy control group.Detailed records of all patients’ age,gender,duration,laboratory indicators and related examinations.(2)DXA was used to measure the bone mineral density of lumbar vertebrae and femoral neck in all patients.The levels of bone metabolism markers(CTX,PINP,OC)in all patients and healthy controls were determined by chemiluminescence immunoassay(CLIA).Bone mineral density and bone metabolism markers were correlated with relevant risk factors to identify relevant risk factors.(3)Each group of patients was grouped according to the measured bone density,and the bone metabolism level of patients with different bone mass was analyzed.(4)Statistical analysis using SPSS 19.0 and GraphPad Prism 7.0 software packages.Results(1)The bone density of lumbar vertebrae and femoral neck in patients with total CTD was lower than that of normal people,but the difference was not statistically significant.The bone density of lumbar vertebrae and femoral neck in patients with various diseases was lower than that of normal age,but the difference was not statistically significant.(2)The bone mineral density at lumbar vertebrae L1-L4 was negatively correlated with age,duration of disease,ESR and cumulative hormones in patients with generalized CTD(P<0.05).Bone density at lumbar vertebrae L1-L4 was negatively correlated with age,duration of disease,and cumulative hormonal use in patients with SLE(P<0.05);bone density at lumbar vertebrae L1-L4 was negatively correlated with age,duration of disease,ESR and cumulative hormonal dose in patients with RA(P<0.05);bone mineral density at lumbar vertebrae L1-L4 was significantly negatively correlated with age in patients with pSS(P<0.01).(3)The level of CTX in bone metabolism and osteoclasts in patients with CTD was significantly higher than that in healthy controls(P<0.01).The level of OB of bone metabolism in SLE patients was significantly lower than that in healthy controls(P<0.01).Among the specific diseases of connective tissue disease,the levels of CTX and OC in SLE patients were lower than those in RA patients and pSS patients(P<0.05),and the PINC levels of osteogenic indicators were lower than those in RA patients(P<0.01).(4)The level of CTX in patients with CTD was positively correlated with age,ESR,CRP and C4(P<0.05).The level of PINP was positively correlated with the course of disease,C3 and C4(P<0.01),and C1 q,current hormone dosage.There was a negative correlation between cumulative hormonal dose and daily hormonal dose(P<0.05).OC level was positively correlated with age,RF,C3,C4(P<0.01),and C1 q,current hormone dosage,cumulative hormone dosage.The daily dose of hormones was significantly negatively correlated(P< 0.01).There was a significant positive correlation between CTX level and ESR in patients with SLE(P<0.01).PINP level was negatively correlated with C1q(P<0.05).OC level was positively correlated with disease course(P<0.01),and was significantly negative correlated with C1q(P<0.01).(5)The level of CTX was positively correlated with ESR in patients with RA(P<0.05).The level of PINP was positively correlated with the course of disease(P<0.01).The level of OC was positively correlated with the course of disease(P<0.05)and the level of OC was negative correlated with C3(P<0.01).The PNP level of pSS patients was negatively correlated with the current hormone dosage(P<0.05),and the OC level was positively correlated with age and C4(P<0.05),which was negatively correlated with the current hormone dosage and daily hormone consumption(P<0.05)..(6)In the overall CTD group,the levels of CTX,PINP,and OC increased with the increase of bone mass loss.The level of CTX was the highest in the patients with bone loss in SLE patients(P<0.05).The levels of PINP and OC in the osteoporosis group were the highest(P<0.05).There was no difference in CTX levels between RA patients with normal bone mass,decreased bone mass and osteoporosis group;PINP and OC levels were the highest in the osteoporosis group(P<0.05).The levels of CTX,PINP and OC in the pSS osteoporosis group were higher than those in the normal bone mass group and the bone mass reduction group(P<0.05).The level of bone metabolism in the normal bone mass of all groups was higher than that in the healthy control group.The level of CTX in the normal group with normal bone mass was higher than that in the healthy control group(P<0.05).The levels of PINP and OC in the patients with normal CTD,SLE and pSS bone mass were lower than those in the healthy control group(P<0.05).Conclusions(1)The overall CTD and bone density of patients with various diseases showed a trend of decreasing.(2)Bone mineral density in patients with CTD is affected by many factors.In addition to RA,the bone mineral density at the femoral neck of each disease is mainly related to vascular inflammation.(3)The total amount of bone in patients with CTD is mainly in the high metabolic state of increased osteotomy and increased osteogenesis.(4)The use of glucocorticoids in CTD patients has a direct inhibitory effect on osteogenesis,and vascular inflammation is one of the important factors affecting osteogenesis.(5)In patients with normal bone mass,the bone mass metabolism has changed.2.Changes of bone metabolism and the effect of TNF inhibitor on bone metabolism in patients with rheumatoid arthritis without glucocorticoidObjective Rheumatoid arthritis(RA)is a chronic autoimmune inflammatory disease in which synovitis and vasospasm are pathological features.Due to their own condition,RA patients are often associated with joint damage and loss of bone mass throughout the body.In this study,we determined the level of bone metabolism markers in patients without glucocorticoid RA,systematically understood the bone metabolism of patients without glucocorticoid RA,and identified the risk factors through correlation analysis.Further explore the changes of bone metabolic index and related indicators in patients with RA after receiving TNF-α inhibitor,and provide a theoretical basis for other CTD patients to evaluate bone mass after treatment with TNF-α inhibitor.Methods(1)65 patients without glucocorticoid RA were enrolled,including 9 males and 56 females,male: female = 1:6.2,mean age(55.04 ± 10.09)years,duration of 1 month to 6 years,the median duration is 3 years.There were 57 healthy controls,including 8 males and 49 females,male: female =1: 6.1,and the average age was(53.5 ± 9.17)years.(2)The CLIA method was used to measure the serum levels of CTX,PINP and OC in the peripheral blood of the study subjects and healthy controls.The differences between the indicators of bone metabolism between RA patients and healthy controls were compared.(3)Collect general data such as age,gender,menstrual status,body mass index(BMI),and laboratory test data such as ESR,CRP,RF and Anti-CCP antibodies to calculate RA disease activity(disease activity score 28,DAS28)score.The disease course,ESR,CRP,RF,Anti-CCP antibody,DAS28 score and other indicators werecorrelated with bone metabolism markers.(4)RA patients were injected with recombinant human type II tumor necrosis factor receptor-antibody fusion protein(Qiangke)subcutaneously,25 mg each time,twice a week,every interval of 3 to 4 days,12 weeks for a course of treatment.The levels of bone metabolism markers and related inflammation indicators in peripheral blood before and after treatment were measured.(5)Statistical analysis was performed using SPSS 19.0 statistical software package and GraphPad Prism 7.0 software package.Results(1)The serum CTX level of RA patients was higher than that of healthy controls(P<0.05),and the serum PINP level was lower than that of the control group(P<0.05).(2)Serum CTX levels in RA patients were positively correlated with age,DAS28 score,ESR and CRP(P<0.01),and had no significant correlation with BMI,RF and anti-CCP antibodies.Serum PINP and OC levels were positively correlated with disease duration(P<0.05).(3)After treatment with TNF-a inhibitor(Qiangke),the serum levels of PINP and OC in RA patients were higher than those before treatment(80.79 ± 63.88 vs 60.23 ± 45.93,P<0.05;22.13 ± 14.46 vs 16.74 ± 8.46,P<0.05).ESR and CRP levels were lower than before treatment(35.53 ± 20.78 vs 60.58 ± 32.42,P<0.01;18.22 ± 10.98 vs 35.54 ± 20.23,P<0.01);DAS28 score was lower than before treatment(4.03 ± 1.05 vs 5.52 ± 1.12,P<0.05).Conclusions(1)Patients who did not use glucocorticoid RA were also active in osteoclasts and osteogenesis.The inflammation of RA itself was the main factor affecting bone destruction.(2)The bone metabolism in patients without glucocorticoid RA is unbalanced,and the osteoclast is significantly more active than the osteogenic bone,and changesbefore osteogenesis,which in turn drives the osteogenesis to rise.(3)After treatment with anti-TNF-α in patients with glucocorticoid RA,the bone metabolism state of the patient can be improved and the bone quality is beneficial.