Network Meta-Analysis of the Effects of Icariin on Osteoblasts and Osteoclasts via the OPG/RANKL/RANK Signaling Pathway
SUN Jing
BAO Shaoyu
ZHANG Zhihai
YU Tong
Abstract：Objective To systematically evaluate and rank the effects of different doses of icariin(ICA)on bone mineral density(BMD),alkaline phosphatase(ALP),and tartrate-resistant acid phosphatase(TRAP)in animal models of osteoporosis via the osteoprotegerin/receptor activator of nuclear factor kappa-B ligand/receptor activator of nuclear factor kappa-B signaling pathway using Bayesian random-effects network meta-analysis.Methods PubMed,Embase,Web of Science,Cochrane Library,CNKI,Wanfang Data,and VIP Database were searched to identify randomized controlled trials of osteoporosis in ovariectomized rodents that compared different concentrations of ICA and multiple interventions(such as estrogen,bisphosphonates,and kidney-tonifying bone-strengthening Chinese patent medicines)with control groups.Study quality was assessed using the SYRCLE risk of bias tool.Outcome measures including femoral BMD,ALP activity,and TRAP activity were extracted for network meta-analysis.Results Seventeen studies involving 564 rats were included,covering 11 intervention regimens including three low-,medium-,and high-dose ICA regimens,estrogen,alendronate sodium tablets,and most Chinese patent medicines.Network meta-analysis showed that medium-dose ICA increased femoral BMD and ALP activity(SMD=0.305,95%CI:0.071-0.391,P<0.001;SMD=46.167,95%CI:-6.205-74.766,P=0.068)and inhibited TRAP activity(SMD=-2.001,95%CI:-2.407--1.594,P<0.001).The surface under the cumulative ranking curve indicated that medium-dose ICA was the optimal regimen for BMD,ALP,and TRAP.Node-splitting and global inconsistency tests suggested good network consistency(P>0.10).Conclusion Current animal evidence indicates that ICA exerts dose-dependent bidirectional bone protection by upregulating the osteoprotegerin/receptor activator of nuclear factor kappa-B ligand ratio,inhibiting the osteoclast nuclear factor kappa-B/mitogen-activated protein kinase cascade,and activating the osteoblast bone morphogenetic protein 2/Smad/runt-related transcription factor 2 pathway.
Keywords：icariinbone mineral densityalkaline phosphatasetartrate-resistant acid phosphatasenetwork meta-analysisrats
Publication Date：2025-12-20
Online Publishing Date：2025-12-25(First online date of this platform, not the publication date of the document)
Pages：9( 159-167 )