Glucagon-like peptide-1(GLP-1) receptor agonists: potential to reduce fracture risk in diabetic patients?
This review summarizes current knowledge about glucagon-like peptide 1 receptor agonists (GLP-1 RA) and their effects on bone metabolism and fracture risk. Recent in vivo and in vitro experiments indicated that GLP-1 RA could improve bone metabolism. GLP-1 could affect the fat-bone axis by promoting osteogenic differentiation and inhibiting adipogenic differentiation of bone mesenchymal precursor cells (BMSCs), which express the GLP-1 receptor. GLP-1 RA may also influence the balance between osteoclasts and osteoblasts, thus leading to more bone formation and less bone resorption. Wnt/β-catenin signalling is involved in this process. Mature osteocytes, which also express the GLP-1 receptor, produce sclerostin which inhibits Wnt/β-catenin signalling by binding to low density lipoprotein receptor-related protein (LRP) 5 and preventing the binding of Wnt. GLP-1 RA also decreases the expression of sclerostin (SOST) and circulating levels of SOST. In addition, GLP-1 receptors are expressed in thyroid C cells, where GLP-1 induces calcitonin release and thus indirectly inhibits bone resorption. Furthermore, GLP-1 RA influences the osteoprotegerin(OPG)/receptor activator of nuclear factor-κB ligand (RANKL)/receptor activator of nuclear factor-κB (RANK) system by increasing OPG gene expression, and thus reverses the decreased bone mass in rats models. However, a recent meta-analysis and a cohort study did not show a significant relationship between GLP-RA use and fracture risk. Future clinical trials will be necessary to investigate thoroughly the relationship between GLP-1 RA use and fracture risk in diabetic patients.
Guojing
G
Luo
Hong
H
Liu
Hongyun
H
Lu
D000818:Animals; D015519:Bone Density; D002116:Calcitonin / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D050723:Fractures, Bone / Q000517:prevention & control*; D052216:Glucagon-Like Peptide 1 / Q000502:physiology; D006801:Humans; D010024:Osteoporosis / Q000209:etiology; D053245:RANK Ligand / Q000502:physiology; D012306:Risk; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000502:physiology; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
D053245:RANK Ligand; D051176:beta Catenin; D052216:Glucagon-Like Peptide 1; D002116:Calcitonin; D000097789:Glucagon-Like Peptide-1 Receptor Agonists