Cellular signaling crosstalk between osteoporosis and diabetes: Common mechanisms and therapeutic targets (Review)

Osteoporosis and diabetes typically occur together. The present review aimed to summarize the molecular mechanisms and intracellular signaling pathways that connect osteoporosis and diabetes. In diabetic conditions, persistent hyperglycemia triggers excessive oxidative stress, sustains low-grade inflammation and perturbs insulin signaling pathways. In turn, bone metabolic abnormalities affect glucose regulation through the bone-pancreas axis and osteoimmune signaling pathways, highlighting a bidirectional relationship between skeletal and metabolic health. Several antidiabetic agents (metformin, glucagon-like peptide-1 receptor agonists) protect against bone loss, while certain anti-osteoporotic drugs (bisphosphonates, denosumab) exert favorable effects on glucose metabolism and diabetic complications. These dual benefits suggest overlapping molecular pathways and shared therapeutic targets. The present review aimed to summarize the inflammation-insulin signaling axis, RANKL/OPG system, Wnt/β-catenin pathway, AGE/RAGE signaling and bone-derived endocrine factors as key mediators of interorgan communication. It also underscores the importance of systems biology and integrated cross-tissue analyses in uncovering the mechanisms underlying diabetes-associated bone disorder. Future research defining the molecular basis of intercellular and interorgan crosstalk may lead to precise, mechanism-driven strategies for the integrated treatment of diabetes and osteoporosis.