前蛋白转化酶枯草溶菌素9在继发性骨质疏松中的调控机制及研究进展OA

Secondary osteoporosis is primarily caused by medications and chronic systemic diseases and is charac-terized by disrupted bone homeostasis and increased skeletal fragility,leading to a substantially elevated risk of osteoporot-ic fractures.However,effective mechanism-based targeted therapeutic strategies remain limited.Crosstalk between lipid metabolism and bone metabolism has emerged as a key mechanism underlying the development and progression of seconda-ry osteoporosis.As a pivotal regulator of lipid metabolism,proprotein convertase subtilisin/kexin type 9(PCSK9)has re-cently attracted considerable attention as a novel molecular target linking lipid and bone metabolic pathways.This review systematically summarizes the molecular mechanisms by which PCSK9 regulates bone metabolism,with emphasis on its bi-directional modulation of osteoblast and osteoclast function through classical signaling pathways,including Wnt/β-cate-nin,PI3K/Akt/mTOR,and NF-κB,as well as its role in mediating inflammation and lipid metabolic disorders.Further-more,the disease-specific pathogenic roles of PCSK9 in four common forms of secondary osteoporosis-glucocorticoid-induced osteoporosis,diabetic osteoporosis,chronic kidney disease-associated osteoporosis,and rheumatoid arthritis-associated osteoporosis-are comprehensively reviewed.A particular focus of this review is the differential regulatory net-works of PCSK9 across distinct subtypes of secondary osteoporosis and the heterogeneous clinical effects of PCSK9 inhibi-tors according to age and sex stratification.These findings provide new mechanistic insights and theoretical support for the precision prevention and treatment of secondary osteoporosis.