Hedgehog signaling pathway and diabetic osteoporosis: a potential target for specific drug therapy

• Hedgehog signaling pathway activation promotes osteoblast differentiation and bone formation via Runx2 and Wnt crosstalk, offering a dual therapeutic approach for diabetic osteoporosis. • The pathway enhances glucose metabolism and insulin sensitivity through PI3K-Akt and AMPK signaling, addressing the diabetic component of the disease. • Hedgehog signaling reduces advanced glycation end products, mitigating oxidative stress and β-cell apoptosis, thus preserving glycemic control. • Targeting Hedgehog with activators, such as tetrahedral framework nucleic acid/quercetin complexes, shows preclinical promise as a specific drug therapy for diabetic osteoporosis.