A variability in response of osteoclasts to zoledronic acid is mediated by smoking-associated modification in the DNA methylome.

ABSTRACT:

Background

Clinical trials have shown zoledronic acid as a potent bisphosphonate in preventing bone loss, but with varying potency between patients. Human osteoclasts ex vivo reportedly displayed a variable sensitivity to zoledronic acid > 200-fold, determined by the half-maximal inhibitory concentration (IC50), with cigarette smoking as one of the reported contributors to this variation. To reveal the molecular basis of the smoking-mediated variation on treatment sensitivity, we performed a DNA methylome profiling on whole blood cells from 34 healthy female blood donors. Multiple regression models were fitted to associate DNA methylation with ex vivo determined IC50 values, smoking, and their interaction adjusting for age and cell compositions.

Results

We identified 59 CpGs

SUBMITTER: Tan Q 

PROVIDER: S-EPMC10012449 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature