Intercellular communication networks in the osteoporotic bone microenvironment

Osteoporosis is essentially a persistent imbalance between bone resorption and bone formation in the bone microenvironment. Its development is not driven by abnormalities in a single cell type, but is closely linked to dysregulated communication among bone cells, marrow stromal cells, immune cells, and vascular cells, together with altered extracellular matrix (ECM) signaling. Existing studies have mainly focused on individual cell types or single signaling pathways, and systematic integration of evidence on osteoporosis from the perspective of intercellular communication and extracellular matrix signaling is still limited. This review organizes representative pathological evidence into three categories based on the main modes of signal transmission: paracrine and autocrine communication, direct cell-cell communication, and ECM-cell communication.

Across these categories, this review highlights communication axes in which source cells, key signals, recipient cells, and bone remodeling outcomes can be linked into relatively clear mechanistic chains. It also considers differences in the strength and completeness of evidence across these axes.

Integrating these pathological changes may clarify how dysregulated intercellular communication and ECM signaling jointly contribute to bone remodeling imbalance in osteoporosis, thereby helping to identify potential targets for intervention.