Effects Of Tumor Necrosis Factor ? Blockers On Bone Mineral Density And Bone Metabolism In Rheumatoid Arthritis: A Systematic Review

Objective:To evaluate the effects of tumor necrosis factor-?(TNF-?)blockers on rheumatoid arthritis(RA)in bone mineral density(BMD)and bone metabolism.Methods:A systematic literature search was performed,using PUBMED,Embase,Cochrane Library,CBM,CNKI,Weipu Database,and Wanfang database(up to August28,2018 for all resources above),to search randomized controlled trial(RCT)about TNF-?blockers for the treatment of RA which reported outcomes of BMD or bone metabolism markers.Two reviewers independently identified the included trials,evaluated bias risk and extracted relevant data.Data analysis was performed using Review Manager 5.3 software.The primary outcome were BMD of femoral greater trochanter,Ward triangle,femoral neck,lumbar vertebrae,hand,hip,and cervical vertebrae.Secondary outcome were bone metabolism markers(including CTX-1,P1NP).Results:A total of 8 articles including 9 RCTs out of 2110 identified references were included in the systematic review.All RCTs were of high bias risk.These 8 literatures compared TNF-?inhibitors with blank,placebo,methotrexate and methotrexate+sulfasalazine+hydroxychloroquine group.For the outcome of BMD difference between baseline and endpoint,the pooled mean differences(MDs)and 95%confidence interval(CI)of femoral greater trochanter,Ward's triangular and the femoral neck were 0.13(0.06,0.21)g/cm~2,0.07(0.03,0.12)g/cm~2,and 0.11(0.03,0.18)g/cm~2,respectively.Pooled MD of femoral neck BMD(percentage change from baseline)was3.08(1.04,5.12)%.For lumbar spine,pooled MDs of endpoint BMD and BMD change from baseline were 0.06(0.01,0.11)g/cm~2,and-0.35(-1.34,0.64)%.Pooled MD hip BMD(change from baseline)was 1.23(-0.69,3.15)%.MD of cervical spine BMD(change from baseline)was 0.11(0.03,0.20)g/cm~2.The MD of the hands BMD(percentage change from baseline)was 0.7(-0.17,1.57)%,.For average change of each month,MD of the hands BMD was-0.04(-0.64,0.56)mg/cm~2.Therefore,TNF-?blockers were superior to the control group in the BMD of femur trochanter,Ward triangle,femoral neck and cervical vertebrae.The difference was statistically significant.Although BMD in the lumbar spine,hand bone and hip was higher than the control group,the difference was not statistically significant.In terms of secondary outcomes,meta analysis showed that the MD of CTX-1 and P1NP were-9.17(-16.27,-2.08)ng/ml and-0.10(-0.16,-0.03)ng/ml.Respectively,they were lower in TNF-?blockers and the difference was statistically significant.Conclusion:TNF-?blockers might reduce bone resorption,alleviate bone destruction,and stabilize bone metabolism.There is an evidence showing TNF blockers delay BMD decline of femur and cervical vertebra.However,there is not enough evidence for lumbar vertebrae,hip joint and hand,more trials of higher quality and longer disease duration are needed.