Cancer and Bone*

Abstract

CANCER is associated with significant morbidity in the skeleton. This was evident as early as 1889 when Stephen Paget (1) observed that “in a cancer of the breast the bones suffer in a special way, which cannot be explained by any theory of embolism alone… the same thing is seen much more clearly in those cases of cancer of the thyroid body where secondary deposition occurs in the bones with astonishing frequency.” He also noted that “a general degradation of the bones sometimes occurs in carcinoma of the breast, yet without any distinct deposition of cancer in them.” These early observations were profound as it is now clear that cancer can involve bone through both metastatic and humoral mechanisms. Since the time of Paget, it has become clear that cancer affects bone in several ways: 1) indirectly through elaboration of factors that act systemically on target organs of bone and kidney to disrupt normal calcium homeostasis; 2) locally and directly via secondary spread of tumor to bone; and 3) via direct involvement by primary bone tumors. As primary bone tumors comprise a small minority of all tumors affecting bone, this review will focus on the aspects of cancer and bone related to the former only.