Meta Analysis Of The Correlation Between Serum MMP-9 And Chronic Obstructive Pulmonary Disease Complicated With Osteoporosis

Objective:Through the Meta analysis of matrix metalloproteinase-9（MMP-9）in chronic obstructive pulmonary disease（COPD）complicated with osteoporosis,the purpose of this study is to provide support for the mechanism of MMP-9 in COPD complicated with osteoporosis.Methods:This study is an observational,analytical,case-control study,using the establishment of inclusion exclusion criteria,computer retrieval,preliminary screening of the literature according to the standards,reading the full text to determine the inclusion of the literature,quality evaluation,statistical analysis,the results of the standard Meta analysis process.The subjects were published COPD,osteoporosis and serum MMP-9related studies in Chinese and English,which met the diagnostic criteria of COPD and osteoporosis diagnosis of adult patients,including at least one group of controls.The main outcome indicators included lung function,bone mineral density,and secondary indicators of serum MMP-9,which were related to MMP-9 expression and osteoporosis.The search databases are Web of Science,EMBASE.com,Pub Med,Cochrane Library,China knowledge Network,Wanfang Database,VIP Database,China Biomedical Literature Database（CBM）,Conference papers Retrieval Database,including Chinese and Foreign Conference papers Database,China important Conference papers full-text Database（CPCD）.The dissertation retrieval database includes Chinese doctoral thesis full-text database（CDFD）and Chinese excellent master’s thesis full-text database（CMFD）.The quality of the included literature was evaluated with reference to the（JBI）quality evaluation standard of the Australian evidence-based Health Care Center in 2016.Stata15.1 software was used for statistical analysis.Results:A total of 57 articles were selected and finally included 6 articles in accordance with the criteria,including 4 Chinese articles with normal bone mass group,COPD with low bone mass group and COPD with osteoporosis group,and 2 English articles with COPD group（diagnosed as COPD,with osteoporosis）and healthy group（healthy people）.The quality evaluations included in the study were all medium or high.The heterogeneity test of all indexes was p<0.05,and the main index MMP-9 had no publication bias.In terms of general indexes,the age of COPD with osteoporosis group was 2.86years older than that of COPD with normal bone mass group,the age of COPD with osteoporosis group was 0.29 years older than that of COPD with low bone mass group,the smoking index of COPD with osteoporosis group was 1.99 more than that of COPD with normal bone mass group,and the smoking index of COPD with osteoporosis group was 0.28 more than that of COPD with low bone mass group.The BMI of COPD patients with osteoporosis was 5.68 points lower than that of COPD patients with normal bone mass,and the BMI of COPD patients with osteoporosis was 0.62points lower than that of COPD patients with low bone mass.The difference was statistically significant.As for the main indicators,the FEV₁%predicted value of COPD with osteoporosis group was 4.49%less than that of COPD with normal bone mass group.The FEV₁%predicted value of COPD with osteoporosis group was 0.30%less than that of COPD with low bone mass group.The FEV₁/FVC of COPD patients with osteoporosis was3.2%less than that of COPD with normal bone mass.The BMD of lumbar vertebrae in COPD with osteoporosis group was 0.373 g/cm²less than that in COPD with normal bone mass group.The BMD of lumbar vertebrae in COPD with low bone mass group was 0.624 g/cm²less than that in COPD with low bone mass group.The BMD of femoral neck in COPD with osteoporosis group was 0.377 g/cm²less than that in COPD with normal bone mass group,and the difference was statistically significant.The serum MMP-9 of COPD with osteoporosis group was 51.987μg/L higher than that of COPD with normal bone mass group,the serum MMP-9 of COPD with osteoporosis group was5.890μg/L higher than that of COPD with low bone mass,and the serum MMP-9 of COPD patients was 18.049μg/L higher than that of normal people in two English literatures comparing the serum MMP-9 of COPD patients with osteoporosis and normal people.As for secondary indexes,the level of serum TIMP-1 in COPD with osteoporosis group was 21.387μg/L higher than that in COPD with normal bone mass group.The level of serum TNF-αin COPD with osteoporosis group was 10.121μg/L higher than that in COPD with normal bone mass group.The serum TNF-αlevel in COPD with osteoporosis group was 0.927μg/L higher than that in low bone mass group.The sBAP of COPD with osteoporosis group was 27.667 lower than that of COPD with normal bone mass group,and the sBAP of COPD with osteoporosis group was lower than that of COPD with low bone mass group.The sOC of COPD with osteoporosis group was 10.990μg/L lower than that of COPD with normal bone mass group,the sOC of COPD with osteoporosis group was 0.678μg/L lower than that of COPD with low bone mass group,the sCTX of COPD with osteoporosis group was 0.236μg/L higher than that of COPD with normal bone mass group,the sCTX of COPD with osteoporosis group was 5.542μg/L higher than that of COPD with low bone mass group.Conclusion:1.Most of the literatures on COPD complicated with osteoporosis focused on men.The incidence and severity of osteoporosis were positively correlated with age and smoking index,and negatively correlated with BMI.2.The incidence and severity of osteoporosis in COPD were negatively correlated with FEV₁/FVC and bone mineral density.The worse the results of FEV₁/FVC and bone mineral density,the higher the incidence and severity of osteoporosis in COPD.The incidence and severity of COPD complicated with osteoporosis were positively correlated with the concentration of serum MMP-9.The value of MMP-9 in patients with COPD was significantly higher and the related indexes of bone mineral density were significantly lower,suggesting that the pathogenesis and progression of COPD with osteoporosis is accompanied by the high expression of MMP-9,and the tissue inhibitor of metalloproteinases（TIMP-1）is also over-expressed with the occurrence of osteoporosis,which may be the adaptive change of the increase of MMP expression.3.The incidence and severity of osteoporosis in COPD were positively correlated with the expression of TNF-α,and negatively correlated with sBAP and sOC.The sCTX of patients with COPD with osteoporosis is 5.542μg/L higher than that of patients with low bone mass,and only 0.236μg/L higher than that of normal bone mass group,suggesting that with the progress of COPD complicated with osteoporosis,the value of sCTX may decrease at first and then increase.