Purpose: Identification of osteoclast derived coupling factors using Denosumab as a biological probe Method: harvested RNA from centrifuged bone biopsies (heterogeneous population containing bone lining cells, osteoblasts, osteoclasts and osteocytes, without in vitro culture Results: Identification of genes differentially regulated in denosumab treated participants that correlate with bone remodeling indices Conclusions: Using this approach we identified denosumab regulated genes that correlate with bone remodeling in the untreated participants and may represent novel osteoclast derived coupling factors. Of interest, we identified DPP4 to be suppressed in denosumab treated participants, providing a novel link between bone remodeling and energy metabolism. Overall design: Examination of gene expression of centrifuged bone biopsies isolated three months after treatment with placebo or denosumab in post-menopausal women