Bone metastases are a common manifestation of distant relapse from many types of solid cancers, especially those arising in the lung, breast, and prostate. As many as 80% of patients with solid tumours will develop painful bone metastases to the spine, pelvis, and extremities during the course of their illness.[1]
Metastatic bone tumours can arise in three ways: 1) On routine follow-ups of patients with a diagnosis of cancer with a suspicion of metastasis (bone scan etc.); 2) While evaluating pain, limitataion of motion in the extremities and pathologic fracture in a patient diagnosed as having cancer; 3) Diagnosing cancer in another part of the body in patients known to be otherwise normal having acute pain, function loss, pathologic fracture.
The exact incidence of bone metastasis is unkown, but it is estimated that 350 000 people die with bone metastases annually in the USA. Furhermore, once tumours metastasize to bone, they are usually incurable: only 20% of patients with breast cancer are still alive after five years ofthe discovery of bone metastasis.[2] Cancer cells follow two main dissemination pathways: 1) the lymphatic pathway, leading to the invasion of the lymph nodes draining the organs where the tumour evolves; and 2) the blood pathway, leading to the invasion of distant organs such as liver, brain, bone or lung.[3] Haematogenous pathway is the most common mechanism.
In particular, inflammation and infiltration of the tumour tissue by host immune cells, such as tumour-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, have been shown to support tumour growth in addition to invasion and metastasis. Each step of tumour development, from initiation through metastatic spread is promoted by communication between tumour and immune cells via the secretion of cytokines, growth factors, and proteases that remodel the tumour microenvironment. Invasion and metastasis require neovascularization, breakdown of the basement membrane, and remodeling of the extracellular matrix for tumour cell invasion and extravasation into the blood and lymphatic vessels.[4]