Theoretical and Natural Science · Jul 6, 2026

The Role of Cellular Senescence in the Pathogenesis of Osteoporosis and Research on Therapeutic Targets

By W H

Osteoporosis is an age-related bone metabolic disease, and cellular senescence is considered a common driver of its occurrence and development. This paper reviews the mechanism of cellular senescence in osteoporosis and advances in targeted therapy. Senescent bone marrow mesenchymal stem cells exhibit decreased osteogenic differentiation capacity and shifted adipogenic differentiation, degeneration of the lacunar-canalicular system of osteocytes and impaired mechanosensation, as well as imbalanced functions of osteoblasts and osteoclasts. The senescence-associated secretory phenotype disrupts the homeostasis of the bone microenvironment through pro-inflammatory factors and matrix metalloproteinases, activates the RANKL/OPG signaling axis, and inhibits the Wnt/β-catenin pathway. Upstream triggers include DNA damage, oxidative stress, and epigenetic alterations. Targeted therapeutic strategies include the elimination of senescent cells by senolytics (dasatinib + quercetin, fisetin), inhibition of SASP secretion by senomorphics (metformin, rapamycin), and novel delivery systems based on exosomes and nanocarriers. Targeting cellular senescence provides a new direction for the precise prevention and treatment of osteoporosis.

doi.org/10.54254/2753-8818/2026.hz35312Open accessMechanisms