Strontium ranelate: New insights into its dual mode of action

摘要: Abstract Strontium ranelate is a newly developed drug that acts as an effective antiosteoporotic therapy in postmenopausal women with osteoporosis. In contrast to other available treatments for osteoporosis, strontium induces opposite effects on bone resorption and formation. Preclinical studies showed this dual effect results increased mass improved microarchitecture strength intact rodents, prevention of loss osteopenic animals. Histomorphometric analysis unpaired iliac crest biopsies osteoporotic patients treated 3 years the formation, assessed by both mineralization rate osteoblast surface, tended decrease osteoclast compared placebo group. Three-dimensional micro-computed tomography consistently higher number trabeculae, decreased trabecular separation, increase cortical thickness, which provides evidence better Some mechanisms underlie beneficial metabolism have now been identified. vitro analyses activates calcium-sensing receptor. We, however, cell replication downstream ERK1/2 signaling osteoblasts from receptor-null mice, indicating that, addition receptor, another receptor could mediate osteoblastic replication. Other can activate osteogenic differentiation marrow stromal cells activating cyclo-oxygenase 2 (COX-2)-mediated prostaglandin E production. Finally, recent data indicate upregulate osteoprotegerin (OPG) activator nuclear factor kappa B (RANK) ligand expression human cells, suggesting may reduce modulating RANK/RANK-ligand/OPG system, essential osteoclastogenesis. These provide new insights into mechanism action give biochemical support physiology explain formation resorption.