Development of a low-dose anti-resorptive drug regimen reveals synergistic suppression of bone formation when coupled with disuse

Abstract

a low-dose anti-resorptive drug regimen reveals synergistic sup-pression of bone formation when coupled with disuse. J Appl Physiol 104: 729–738, 2008. First published January 3, 2007; doi:10.1152/japplphysiol.00632.2007.—Safe and effective counter-measures to spaceflight-induced osteoporosis are required to mitigate the potential for mission-critical fractures and ensure long-term bone health in astronauts. Two anti-resorptive drugs, the bisphosphonate zoledronic acid (ZOL) and the anti-receptor activator of NF-B ligand protein osteoprotegerin (OPG), were investigated to find the mini-mum, comparable doses that yield a maximal increase in bone quality, while minimizing deleterious effects on turnover and mineralization. Through a series of five trials in normally loaded female mice (n 56/trial), analysis of trabecular volume fraction and connectivity using microcomputed tomography, along with biomechanical testing, quan-titative histomorphometry, and compositional analysis, was used t