Abstract Breast cancer is the first of the top ten cancer killers among the female population of OECD member countries. Breast cancer cells have spread to bone easily. The bone is the preferred site of metastasis for breast cancer and is associated with significant morbidity and poor prognosis. The interaction between breast cancer cells and the bone microenvironment results in a ‘vicious cycle’ that increases both bone destruction and tumor burden. Breast cancer induces up-regulation of receptor activator of nuclear factor-κB ligand (RANKL) in osteoblast by several osteolytic factors derived from breast cancer cells, and subsequently osteoclast formation through the interaction between RANKL in osteoblasts and RANK in osteoclast precursors. Growth factors, such as transforming growth factor-β and insulin-like growth factor-1, are released from bone matrix by osteoclast-derived bone erosion. Natural plant-derived components have received much attention as sources of potential therapeutic and preventive drugs for human diseases. Magnoliae Flos (MF), the buds of Magnolia denudata Desr., is a commonly used Asian medicinal herb for symptomatic relief of allergic rhinitis, sinusitis and headache. To evaluate the inhibitory effects of MF extract and its active components (aschatin, fargesin, lirioresinol B dimethyl ether and magnolin) on cancer-associated bone disease, we first examined their effects on RANKL-induced osteoclastogenesis and bone resorption. MF extract and active components inhibited RANKL-mediated osteoclast differentiation in mouse bone marrow macrophages in a dose dependant manner without any evidence of cytotoxicity, and bone-resorbing activity of osteoclast. In addition, MF extract and active components suppressed the mRNA expression of osteolytic factors in MDA-MB-231 human breast cancer cells, but did not affect the viability of MDA-MB-231 cells. These results demonstrate that MF extract and its active components has the potential to serve as beneficial supplements to treat and prevent cancer-induced bone diseases in patients with metastatic breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5582. doi:10.1158/1538-7445.AM2011-5582