Common cancer metastases in bone include those derived from the breast or prostate.

Associated with such metastases is considerable pain for the patient, a high incidence of pathological fractures (breast cancer metastases), and complications of spinal cord compression and paraplegia.

Attention has focussed on the properties of breast or prostate cancer cells that permit them to migrate from their primary site and to invade and grow in bone. Both breast and prostate cancer cell lines and primary cancers exhibit a number of phenotypic properties in common with bone cells, and it has been proposed that these properties may contribute to a breast cancer’s capacity to establish and grow in bone. Once established in bone, these cancers may induce an osteosceloritic or osteolytic lesion. Osteolysis is also noted in the establishment of an osteosclerotic lesion that is frequently associated with prostate cancers. Thus, paramount for a cancer to establish in bone is the requirement for limited bone destruction, and the magnitude of associated bone destruction is a function of the cancer cell.

Although it has been postulated that bone destruction by cancer cells is mediated directly by tumor cells, evidence indicates that breast cancer-induced bone destruction is mediated by the osteoclast. Support for the latter include: 1) breast cancers express cytokines [such as IL-1, IL-6, LIF, prostaglandin tumor necrosis factor and parathyroid hormone-related protein (PTHrP)] which can influence osteoclast formation; 2) histologic analyses of osteolytic lesions reveal tumor adjacent to osteoclasts resorbing bone; 3) and use of bisphosphonates, potent inhibitors of osteoclastic bone resorption, in women with breast cancer metastases to bone results in reduced skeletal morbidity.

The interaction of cytokines expressed by cancer cells in the bone microenvironment and their action on osteoblast/stromal cells to induce differentiation of haematopoietic cells of the macrophage / monocyte lineage into osteoclasts is now understood. The mechanisms involved in cancer metastasis, osteoclast formation, and ultimately bone destruction will be discussed, along with the potential new therapies to limit bone destruction.