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Review Open Access

Biological mechanisms underlying the effects of low‑magnitude mechanical stress in osteoporosis (Review)

  • Authors:
    • Zhi Liu
    • Dan Han
    • Yanfei Wang
    • Hongfan Li
    • Xuedong Pei
    • Zhijing Song
  • View Affiliations / Copyright

    Affiliations: Clinical College of Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P.R. China, College of Acupuncture‑Moxibustion and Tuina, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 282
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    Published online on: August 28, 2026
       https://doi.org/10.3892/etm.2026.13277
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Abstract

Osteoporosis is characterized by reduced bone strength and an increased risk of fracture. Low‑magnitude mechanical stress (LMMS) has been investigated as a non‑invasive stimulus capable of modulating mechanotransduction in bone cells. This review synthesizes evidence concerning integrin‑cytoskeletal signaling, linker of nucleoskeleton and cytoskeleton‑mediated nuclear force transmission, connexin 43‑mediated intercellular communication and the downstream regulation of bone marrow mesenchymal stem cells, osteoblasts and osteoclasts. Preclinical studies indicate that LMMS can activate the Wnt/β‑catenin, MAPK/ERK, PI3K/AKT and receptor activator of nuclear factor‑κB ligand/osteoprotegerin pathways in a context‑dependent manner. However, clinical responses to whole‑body vibration remain heterogeneous, vary according to the applied dose and skeletal site, and have not yet demonstrated fracture‑prevention efficacy. Pulsed electromagnetic fields and therapeutic exercise are therefore discussed as related biophysical or mixed‑magnitude interventions rather than as forms of LMMS itself. The present review highlights the gap between simplified cellular models and the three‑dimensional bone microenvironment and proposes priorities for reporting standards and trial design to facilitate clinical translation.
View Figures

Figure 1

Biological mechanisms of
low-magnitude mechanical stress stimulation. LMMS activates
integrin/focal-adhesion kinases at the cell-ECM interface, inducing
cytoskeletal remodeling and LINC-mediated nuclear force
transmission. Cx43 channels coordinate intercellular and paracrine
signals. AKT, protein kinase B; ATP, adenosine triphosphate; Cx43,
connexin 43; Dkk2, Dickkopf-related protein 2; ECM, extracellular
matrix; ERK, extracellular signal-regulated kinase; FAK, focal
adhesion kinase; GJIC, gap junctional intercellular communication;
LINC, linker of nucleoskeleton and cytoskeleton; LMMS,
low-magnitude mechanical stress; MAPK, mitogen-activated protein
kinase; PGE2, prostaglandin E2; PI3K,
phosphoinositide 3-kinase; MEK, MAPK/ERK kinase; nesprin, nuclear
envelope spectrin repeat protein; Raf, rapidly accelerated
fibrosarcoma kinase; Ras, rat sarcoma virus protein; RhoA, Ras
homolog family member A; ROCK1, Rho-associated
coiled-coil-containing protein kinase 1; Runx2, RUNX family
transcription factor 2; Src, Src family kinase; SUN, Sad1/UNC84
domain protein; TAZ, transcriptional co-activator with PDZ-binding
motif; VCL, vinculin; Wnt, wingless-related integration site; YAP,
Yes-associated protein; αVβ3, integrin αVβ3; α5β1, integrin α5β1;
p-, phosphorylated.
View References

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Copy and paste a formatted citation
Spandidos Publications style
Liu Z, Han D, Wang Y, Li H, Pei X and Song Z: Biological mechanisms underlying the effects of low‑magnitude mechanical stress in osteoporosis (Review). Exp Ther Med 32: 282, 2026.
APA
Liu, Z., Han, D., Wang, Y., Li, H., Pei, X., & Song, Z. (2026). Biological mechanisms underlying the effects of low‑magnitude mechanical stress in osteoporosis (Review). Experimental and Therapeutic Medicine, 32, 282. https://doi.org/10.3892/etm.2026.13277
MLA
Liu, Z., Han, D., Wang, Y., Li, H., Pei, X., Song, Z."Biological mechanisms underlying the effects of low‑magnitude mechanical stress in osteoporosis (Review)". Experimental and Therapeutic Medicine 32.4 (2026): 282.
Chicago
Liu, Z., Han, D., Wang, Y., Li, H., Pei, X., Song, Z."Biological mechanisms underlying the effects of low‑magnitude mechanical stress in osteoporosis (Review)". Experimental and Therapeutic Medicine 32, no. 4 (2026): 282. https://doi.org/10.3892/etm.2026.13277
Copy and paste a formatted citation
x
Spandidos Publications style
Liu Z, Han D, Wang Y, Li H, Pei X and Song Z: Biological mechanisms underlying the effects of low‑magnitude mechanical stress in osteoporosis (Review). Exp Ther Med 32: 282, 2026.
APA
Liu, Z., Han, D., Wang, Y., Li, H., Pei, X., & Song, Z. (2026). Biological mechanisms underlying the effects of low‑magnitude mechanical stress in osteoporosis (Review). Experimental and Therapeutic Medicine, 32, 282. https://doi.org/10.3892/etm.2026.13277
MLA
Liu, Z., Han, D., Wang, Y., Li, H., Pei, X., Song, Z."Biological mechanisms underlying the effects of low‑magnitude mechanical stress in osteoporosis (Review)". Experimental and Therapeutic Medicine 32.4 (2026): 282.
Chicago
Liu, Z., Han, D., Wang, Y., Li, H., Pei, X., Song, Z."Biological mechanisms underlying the effects of low‑magnitude mechanical stress in osteoporosis (Review)". Experimental and Therapeutic Medicine 32, no. 4 (2026): 282. https://doi.org/10.3892/etm.2026.13277
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