# Traditional Chinese Medicine for osteoporosis management: from molecular mechanisms to drug discovery **Authors:** Shenyu Yan, Qiaohui Du, Lijun Zhao, Qing Liu, Meiling Wu, Ziqiao Xu, Jiangang Shen PMC · DOI: 10.1186/s13020-026-01353-9 · Chinese Medicine · 2026-02-27 ## TL;DR This paper reviews how Traditional Chinese Medicine can help manage osteoporosis by targeting multiple biological processes and offering multi-target therapies. ## Contribution The paper provides a comprehensive review of TCM's molecular mechanisms and herbal compounds for osteoporosis treatment. ## Key findings - TCM formulae like Xianling Gubao Capsule and Qing’e pill reduce fracture risk by promoting bone formation and suppressing bone resorption. - Herbal compounds such as icariin, naringin, and astragaloside IV show therapeutic potential by targeting osteogenesis, osteoclastogenesis, and cellular senescence. - Integrating TCM with modern science can lead to safer, multi-target therapies for osteoporosis. ## Abstract Osteoporosis, a prevalent skeletal disorder, poses significant challenges in aging populations. Traditional Chinese Medicine (TCM) offers a multi-target approach to addressing its complex pathogenesis, which involves hormonal imbalance, oxidative stress, and inflammation. This review highlights the current progress in osteoporosis, focusing on the molecular mechanisms and therapeutic targets of relevant mechanisms, as well as the related cellular events and signaling pathways. Furthermore, the study reviews the clinical effectiveness of several representative TCM formulae, such as Xianling Gubao Capsule and Qing’e pill, which can reduce fracture risk by promoting bone formation and suppressing bone resorption. The study also discusses the therapeutic principles of the promising medicinal herbal compounds, such as icariin for enhancing osteogenesis, naringin for inhibiting osteoclastogenesis, and astragaloside IV for reducing cellular senescence. In summary, TCM's holistic approach offers a valuable strategy for managing osteoporosis, particularly for high-risk patients. Integrating traditional knowledge with modern science enables the development of safer, multi-target therapies addressing both bone quantity and quality. Continued research will facilitate evidence-based TCM interventions for global osteoporosis care. ## Linked entities - **Chemicals:** icariin (PubChem CID 5318997), naringin (PubChem CID 442428), astragaloside IV (PubChem CID 158694) - **Diseases:** osteoporosis (MONDO:0005298) ## Full-text entities - **Genes:** ALPP (alkaline phosphatase, placental) [NCBI Gene 250] {aka ALP, PALP, PLAP, PLAP-1}, NFATC1 (nuclear factor of activated T cells 1) [NCBI Gene 4772] {aka NF-ATC, NF-ATc1.2, NFAT2, NFATc}, ROR2 (ROR family WNT receptor 2) [NCBI Gene 4920] {aka BDB, BDB1, NTRKR2, RRS1}, BGLAP (bone gamma-carboxyglutamate protein) [NCBI Gene 632] {aka BGP, OC, OCN}, STING1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 340061] {aka ERIS, MITA, MPYS, NET23, SAVI, STING}, DKK1 (dickkopf Wnt signaling pathway inhibitor 1) [NCBI Gene 22943] {aka DKK-1, SK}, RUNX2 (RUNX family transcription factor 2) [NCBI Gene 860] {aka AML3, CBF-alpha-1, CBFA1, CCD, CCD1, CLCD}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, CALCA (calcitonin related polypeptide alpha) [NCBI Gene 796] {aka CALC1, CGRP, CGRP-I, CGRP-alpha, CGRP1, CT}, NFKBIA (NFKB inhibitor alpha) [NCBI Gene 4792] {aka EDAID2, IKBA, MAD-3, NFKBI}, MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, NOTUM (notum, palmitoleoyl-protein carboxylesterase) [NCBI Gene 147111] {aka hNOTUM}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, ANGPT1 (angiopoietin 1) [NCBI Gene 284] {aka AGP1, AGPT, AGPT-1, ANG1, HAE5}, NOTCH1 (notch receptor 1) [NCBI Gene 4851] {aka AOS5, AOVD1, TAN1, hN1}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, CLCF1 (cardiotrophin like cytokine factor 1) [NCBI Gene 23529] {aka BSF-3, BSF3, CISS2, CLC, NNT-1, NNT1}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, TRAF6 (TNF receptor associated factor 6) [NCBI Gene 7189] {aka MGC:3310, RNF85}, BECN1 (beclin 1) [NCBI Gene 8678] {aka ATG6, VPS30, beclin1}, PTH (parathyroid hormone) [NCBI Gene 5741] {aka FIH1, PTH1}, TNFRSF11B (TNF receptor superfamily member 11b) [NCBI Gene 4982] {aka OCIF, OPG, PDB5, TR1}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, BMP1 (bone morphogenetic protein 1) [NCBI Gene 649] {aka OI13, PCOLC, PCP, TLD}, GPX4 (glutathione peroxidase 4) [NCBI Gene 2879] {aka GPx-4, GSHPx-4, MCSP, PHGPx, SMDS, snGPx}, SP7 (Sp7 transcription factor) [NCBI Gene 121340] {aka OI11, OI12, OSX, osterix}, JAK2 (Janus kinase 2) [NCBI Gene 3717] {aka JTK10}, BMP2 (bone morphogenetic protein 2) [NCBI Gene 650] {aka BDA2, BMP2A, SSFSC, SSFSC1}, HES1 (hes family bHLH transcription factor 1) [NCBI Gene 3280] {aka HES-1, HHL, HRY, bHLHb39}, WNT5A (Wnt family member 5A) [NCBI Gene 7474] {aka hWNT5A}, Tnfrsf11b (tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)) [NCBI Gene 18383] {aka OCIF, Opg, TR1}, TNFSF11 (TNF superfamily member 11) [NCBI Gene 8600] {aka CD254, ODF, OPGL, OPTB2, RANKL, TNLG6B}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, HEY1 (hes related family bHLH transcription factor with YRPW motif 1) [NCBI Gene 23462] {aka BHLHb31, CHF2, HERP2, HESR1, HRT-1, NERP2}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, WNT10B (Wnt family member 10B) [NCBI Gene 7480] {aka SHFM6, STHAG8, WNT-12}, PDGFB (platelet derived growth factor subunit B) [NCBI Gene 5155] {aka IBGC5, PDGF-2, PDGF2, SIS, SSV, c-sis}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, ATG7 (autophagy related 7) [NCBI Gene 10533] {aka APG7-LIKE, APG7L, GSA7, SCAR31}, Tnfsf11 (tumor necrosis factor (ligand) superfamily, member 11) [NCBI Gene 21943] {aka Ly109l, ODF, OPGL, RANKL, Trance}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, NOTCH2 (notch receptor 2) [NCBI Gene 4853] {aka AGS2, HJCYS, hN2}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, CSF1 (colony stimulating factor 1) [NCBI Gene 1435] {aka CSF-1, MCSF, PG-M-CSF}, PECAM1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 5175] {aka CD31, CD31/EndoCAM, GPIIA', PECA1, PECAM-1, endoCAM}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, EMCN (endomucin) [NCBI Gene 51705] {aka EMCN2, MUC14}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, CCR2 (C-C motif chemokine receptor 2) [NCBI Gene 729230] {aka CC-CKR-2, CCR-2, CCR2A, CCR2B, CD192, CKR2}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, MIR335 (microRNA 335) [NCBI Gene 442904] {aka MIRN335, hsa-mir-335, miRNA335, mir-335} - **Diseases:** mitochondrial dysregulation (MESH:D021081), fragility fractures (MESH:D005600), vertebrae (MESH:C562952), Kidney Deficiency (MESH:D007680), chronic (MESH:D002908), vomiting (MESH:D014839), bone fragility (MESH:C536063), Estrogen deficiency (MESH:D056828), dry mouth (MESH:D014987), BMD (MESH:D001851), nausea (MESH:D009325), abdominal discomfort (MESH:D000007), jaundice (MESH:D007565), fatigue (MESH:D005221), mtDNA defects (MESH:C536350), bone resorption (MESH:D001862), diarrhea (MESH:D003967), constipation (MESH:D003248), Liver-Spleen Dysfunction (MESH:D017093), tinnitus (MESH:D014012), skeletal disorder (MESH:C564967), Dysbiosis (MESH:D064806), diabetic (MESH:D003920), gastrointestinal discomfort (MESH:D005767), calcification (MESH:D002114), primary (MESH:D010538), Bone Impediment (MESH:D001847), hormone (MESH:C565870), abdominal pain (MESH:D015746), Idiopathic osteoporosis (MESH:C537700), anorexia (MESH:D000855), Osteoporosis (MESH:D010024), gastrointestinal, hepatobiliary, dermatological, urinary, and respiratory disorders (MESH:D004066), Osteoporotic (MESH:D058866), inflammation (MESH:D007249), bone pain (MESH:D010146), fracture (MESH:D050723), nutritional deficiencies (MESH:D044342), fractures of the wrist, hip (MESH:D000092503), postmenopausal (MESH:D015663), Liver-Kidney Yin Deficiency (MESH:D016710), mitochondrial dysfunction (MESH:D028361) - **Chemicals:** branched-chain amino acids (MESH:D000597), echinacoside (MESH:C060297), acetate (MESH:D000085), Luteolin (MESH:D047311), resveratrol (MESH:D000077185), casticin (MESH:C054133), Angelicin (MESH:C011659), alcohol (MESH:D000438), gamma-carboxyglutamic acid (MESH:D015055), glucose (MESH:D005947), bisphosphonates (MESH:D004164), magnesium (MESH:D008274), Flavonoids (MESH:D005419), Artesunate (MESH:D000077332), 6-shogaol (MESH:C040115), short-chain fatty acids (MESH:D005232), ROS (MESH:D017382), calcium (MESH:D002118), Tanshinone (MESH:C021751), Vitexin (MESH:C032731), apatite (MESH:D001031), Morusin (MESH:C057451), water (MESH:D014867), ATP (MESH:D000255), Danshensu (MESH:C035055), kaempferol (MESH:C006552), Arbutin (MESH:D001104), steroid (MESH:D013256), lipid (MESH:D008055), Aclasta (MESH:D000077211), bergamottin (MESH:C068337), Astragaloside IV (MESH:C052064), Glycyrol (MESH:C531349), coenzyme Q (MESH:D014451), genistein (MESH:D019833), ursolic acid (MESH:C005466), coumestan (MESH:C505898), apigenin (MESH:D047310), dexamethasone (MESH:D003907), butyrate (MESH:D002087), estradiol (MESH:D004958), Notoginsenoside R1 (MESH:C072936), Psoralen (MESH:D005363), Icaritin (MESH:C499403), Irisolidone (MESH:C423902), Reactive nitrogen species (MESH:D026361), Ginsenoside Rg1 (MESH:C035054), astragalin (MESH:C001579), castanoside A (MESH:C495713), Icariin (MESH:C056599), isoflavone (MESH:D007529), quercetin (MESH:D011794), phenanthrenequinone (MESH:C005399), propionate (MESH:D011422), celastrol (MESH:C050414), alpha-mangostin (MESH:C021053), malondialdehyde (MESH:D008315), daidzein (MESH:C004742), hydrogen peroxide (MESH:D006861), Achyranthis bidentatae (-) - **Species:** Salvia miltiorrhiza (Chinese salvia, species) [taxon 226208], Cistanche deserticola (species) [taxon 161395], Cymbium olla (Algarve volute, species) [taxon 543401], gut metagenome (species) [taxon 749906], Eucommia ulmoides (species) [taxon 4392], Allium sativum (garlic, species) [taxon 4682], Zingiber officinale (ginger, species) [taxon 94328], Lepisorus fortuni (species) [taxon 272675], Curcuma longa (turmeric, species) [taxon 136217], Juglans regia (English walnut, species) [taxon 51240], Eleutherococcus senticosus (species) [taxon 82096], Artemisia annua (sweet Annie, species) [taxon 35608], Radix (genus) [taxon 55689], Morus australis (Aino mulberry, species) [taxon 66392], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Garcinia mangostana (mangosteen, species) [taxon 58228], Glycyrrhiza (licorice, genus) [taxon 46347], Cullen corylifolium (species) [taxon 429560], Panthera tigris (tiger, species) [taxon 9694], Homo sapiens (human, species) [taxon 9606], Lycium barbarum (Duke of Argyll's teatree, species) [taxon 112863], Astragalus membranaceus (species) [taxon 649199], Epimedium brevicornu (species) [taxon 253618], Glycine max (soybean, species) [taxon 3847], Cuscuta chinensis (species) [taxon 267557], Danio rerio (leopard danio, species) [taxon 7955] - **Cell lines:** JTG — Homo sapiens (Human), Hybridoma (CVCL_DD92), MC3T3-E1 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0409), RAW264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12947499/full.md ## Figures 4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12947499/full.md ## References 5 references — full list in the complete paper: https://tomesphere.com/paper/PMC12947499/full.md --- Source: https://tomesphere.com/paper/PMC12947499