**2. Bone remodeling**

Bone remodeling is an important process in maintaining bone health, as approximately 10% of the bone is renewed every year [7]. This is a balanced process coupling bone resorption and bone formation. However, in the absence of bone formation, bone resorption continues to occur normally. This process happens with predilection in the elderly population and with even more affinity in postmenopausal women.

Bone remodeling is characterized by a succession of osteoclastic resorption of already formed bone, followed by de novo bone synthesis by osteoblasts.

Development of bone metastasis refers to a specific interaction between osteoclasts, osteoblasts, and several inflammatory modulators such as Parathyroid PTH, Parathyroid hormone-related protein PTHrP, Cyclooxygenase 2 COX-2/PEG-2, interleukins 1 and 11 (IL-1, IL11), tumor necrosis factors TNF-alpha, TGF-beta [8]. In metastatic breast cancer, osteoblasts secrete macrophage colony stimulating factor (M-CSF), which binds to c-fms, and receptor activator of nuclear factor kappa B ligand (RANKL), which binds to RANK, thus stimulating differentiation of preosteoclasts into osteoclasts. RANKL inhibitors can be therefore successfully used to stop osteoclastic activity [9].
