| Denosumab is a nuclear factor-κB receptor activator ligand (RANKL) inhibitor that binds to RANKL, preventing its interaction with the receptor nuclear factor-κB receptor activator (receptor activator of nuclear factor-κB, RANK). When the coupling of bone resorption and bone formation is disrupted, bone resorption exceeds bone formation. RANKL binds to RANK on the surface of osteoclast precursor cells, inducing NF-κB activation through the intracellular signaling pathway of RANK, thereby regulating the expression of genes related to osteoclast differentiation and promoting osteoclast differentiation, maturation, and activation. Osteoprotegerin (OPG), secreted by osteoblasts, competitively binds to RANKL. The RANKL/OPG ratio directly influences bone resorption, while the RANKL/RANK/OPG signaling pathway plays a crucial role in regulating bone remodeling. This guideline incorporates extensive research evidence, providing precise discussions on pharmacokinetics and supporting evidence, indications and contraindications for osteoporosis clinical applications, dosage and administration, treatment protocols, recommendation levels, discontinuation requirements, sequential therapy, combination therapy, safety, rare adverse reactions, medication use in patients with renal insufficiency, treatment of osteoporotic fractures, and the application of denosumab in conditions such as male osteoporosis and diabetes with fracture risk. |