Metastatic Bone Disease

Metastatic bone disease develops when malignant cells travel to bone, establish deposits in the marrow or skeletal matrix, and disrupt normal remodeling. Breast, prostate, lung, kidney, and thyroid cancers commonly spread to bone. Multiple myeloma also produces destructive lytic bone disease, although it is a plasma-cell malignancy rather than a solid-tumor metastasis. The lesion may be osteolytic, osteoblastic, or mixed. Osteolytic disease is characterized by excessive osteoclast-mediated resorption; it is common with multiple myeloma and many breast, lung, and renal cancers. Osteoblastic disease, classically associated with prostate cancer, produces additional bone, but that bone is poorly organized and does not restore normal strength. Either pattern can result in pathologic fracture or vertebral instability. The mechanism is self-reinforcing. Tumor cells release signals such as parathyroid hormone-related protein (PTHrP), which increase stromal and osteoblast expression of RANKL and reduce osteoprotegerin. RANKL drives osteoclast maturation. As osteoclasts resorb bone, they release matrix-bound transforming growth factor beta and insulin-like growth factors. Those factors stimulate tumor survival and further PTHrP production. The tumor and the osteoclast effectively keep stimulating each other. This explains why a...