%0 Journal Article
%T From bone to breast and back - the bone cytokine RANKL and breast cancer
%A Lorenz C Hofbauer
%A Tilman D Rachner
%A Christine Hamann
%J Breast Cancer Research
%D 2011
%I BioMed Central
%R 10.1186/bcr2842
%X Breast cancer and osteoporotic fractures affect one in eight and one in three women, respectively, during lifetime, ranking these two diseases high on the women's health agenda. In recent years, screening programs have been established and efficient therapies for the treatment of both diseases have become available. Hormone replacement therapy is effective against bone loss in postmenopausal osteoporosis, but is associated with increased incidence of breast cancer. By contrast, some therapies against osteoporosis may protect against breast cancer, including raloxifene [1] and bisphosphonates [2,3].There may be even closer links between these two disorders at the molecular level, involving the receptor activator of nuclear factor-¦ĘB ligand (RANKL). Its major role in human physiology is to control the differentiation and activation of osteoclasts, the bone cells specialized to break down bone [4]. Osteoclasts initiate a sequence of events whereby bone of poor quality is removed and replaced by new bone. This remodeling process constantly repairs the skeleton. The delicate balance between resorption and formation of bone can be severely impaired by declining sex steroid hormones, as in menopause, or during adjuvant therapy for breast or prostate cancer [5]. At the cellular level, up-regulation of RANKL promotes osteoclast differentiation and activity, induces excessive bone resorption, and leads to osteoporotic fractures. This common theme applies to several important bone loss disorders, including postmenopausal osteoporosis and osteoporosis associated with aromatase inhibitor and androgen-ablative therapy, osteolytic metastases, myeloma bone disease, and giant cell tumors of the bone [5]. Based on its fundamental role in skeletal homeostasis, RANKL has become a therapeutic target in the treatment of bone disorders, and a monoclonal antibody against RANKL, denosumab, has been approved for the treatment of postmenopausal osteoporosis [6].Since its discovery, the RANKL/
%U http://breast-cancer-research.com/content/13/3/107