Initial Seeding The primary tumor secretes factors priming the bone and creating a premetastatic niche near highly vascularized trabecular bone. Tumor cells are then attracted to the metastatic niche in the bone marrow, however the characteristics of these niches have yet to be fully elucidated. Initial seeding can occur prior to the discovery of the primary tumor. Vascular Seeding The pathogenesis of<unk>  is hypothesized to be related to the Batson vertebral vein plexus, a longitudinal valveless system connected to the breast, lung, kidney, thyroid, and prostate gland that extends from the sacrum to the skull. The most common locations of<unk>  are pelvis, vertebral bodies, ribs and proximal extremities. Dormancy Once established, the tumor cells can remain dormant on the bone microenvironment, radiologically undetectable, for many years. The triggers which eventually awaken metastatic tumor cells are an active field of study as they could elucidate mechanisms of controlling dormancy. Tumor Cell-Bone Interactions Tumor cells secrete factor like Prostaglandin E, TGF-alpha, TGF-beta, TNF, and interleukins which increase bone resorption. The destruction of bone affected by<unk>  are caused by osteoclast-mediated osteolysis. The uncoupled regulation of the osteoclasts and osteoblasts leads to malformation of the bone. Vicious Cycle Tumor cells secrete PTHrP which stimulates osteoblasts and bone stromal cells to release RANKL. RANKL binds RANK on osteoclast progenitor cells stimulating them to complete their progression into osteoclasts. Osteoclasts break down bone releasing growth factors (i.e. calcium, IGF-1, and TGF-beta) which further stimulate tumors cells thus feeding forward a vicious cycle. This prominent pathway of bone destruction makes bone-targeting agents an essential tool for treatment of<unk> . ;Tumor cells stimulating bone resorption in a Vicious Cycle. Metastatic tumor cells secrete PTHrP which stimulates Osteoblasts and Stromal bone cells.These cells then stimulate the RANK receptor on osteoclast-precursors transition into bone resorbing osteoclasts by secreting RANKL. Bone contains main growth factors and their release further stimulates metastatic tumor cells.
Bone metastasis
Bone tumor
Bone sarcoma
Osteomyelitis
Osteoma
Osteopetrosis
Bone cyst
Tumoral calcinosis