and has not been previously reported. This observation is supported by a previous unrelated study which showed normalization of disease-related changes in gene expression related to therapeutic intervention in an examination of cytokine transcript levels associated with mucosal inflammatory tissue from untreated versus treated Crohn’s disease patients (Stallmach et al., 2004). Taken together these observations suggest that modulation of aberrant gene expression levels associated with disease processes may be an overlooked mechanism of action for some therapeutic agents. The normalization of some integrin signaling genes by ibandronate shown in Table 3 suggests that correction of alcohol-perturbed integrin signaling gene expression by ibandronate may be a key factor in its ability to prevent alcohol-related bone loss. The presence of an alcohol-sensitive, ibandronate-responsive gene cluster comprised of many genes without apparent connections to bone remodeling suggests that ibandronate may prevent bone loss by novel mechanisms of action in addition to the inhibition of osteoclast-mediated resorption.
