Molecular mechanisms of action of bisphosphonates and strontium ranelate

• Published in: Ėksperimentalʹnaâ i kliničeskaâ farmacologiâ Vol. 77; no. 9; p. 43
• Main Authors: Vengerovskiĭ, A I, Khlusov, I A, Nechaev, K A
• Format: Journal Article
• Language: Russian
• Published: Russia (Federation) 2014
• Subjects: Apoptosis - drug effects; Bone and Bones - drug effects; Bone and Bones - metabolism; Bone and Bones - pathology; Bone Density Conservation Agents - therapeutic use; Bone Resorption - drug therapy; Bone Resorption - metabolism; Bone Resorption - pathology; Diphosphonates - therapeutic use; Gene Expression Regulation; Geranyltranstransferase - antagonists & inhibitors; Geranyltranstransferase - genetics; Geranyltranstransferase - metabolism; Humans; Osteoblasts - cytology; Osteoblasts - drug effects; Osteoblasts - metabolism; Osteoclasts - drug effects; Osteoclasts - metabolism; Osteoclasts - pathology; Osteoprotegerin - genetics; Osteoprotegerin - metabolism; RANK Ligand - genetics; RANK Ligand - metabolism; Receptor Activator of Nuclear Factor-kappa B - genetics; Receptor Activator of Nuclear Factor-kappa B - metabolism; Signal Transduction; Thiophenes - therapeutic use; Wnt Proteins - genetics; Wnt Proteins - metabolism
• ISSN: 0869-2092

Bisphosphonates are chemical analogs of isoprene lipids, which competitively decrease the activity of farnesyl diphosphate synthase in osteoclasts and thus retard prenylation. The non-prenylated small GTPases cannot attach to the membrane of osteoclasts, which decreases their resorptive function and accelerates apoptosis. Strontium ranelate activates the Wnt signal pathway (with participation of calcium-sensitive receptor), increases the replication activity (by changing the function of RANKL/RANK/OPG system) thus suppressing the apoptosis of osteoblasts, and retards the resorptive function by accelerating the apoptosis of osteoclasts.