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

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.