Special Issue

Bone metastases—The clinical problem

Cancer-induced bone diseases include primary osseous tumours, non-metastatic effects of malignancy on the skeleton and the effects of anticancer treatment on bone, but by far the most important problem clinically is metastatic bone disease. Cancers of the breast and prostate are particularly likely to spread to bone; approximately 70% of patients who die from these diseases have evidence of skeletal involvement at autopsy (Table 1). Carcinomas of the thyroid, kidney and bronchus also often cause bone metastases with a postmortem incidence of 30–40%, but, by contrast, tumours of the gastro-intestinal tract do so rarely affecting only about 5% of patients dying from these malignancies [1].

The variability in metastatic patterns from different primary cancers, while probably reflecting molecular and cellular biological characteristics of both the tumour cells and the tissues to which they metastasise, is also likely to be a consequence of other mechanisms. The predominant distribution of bone metastases in the axial skeleton, in which most of the red bone marrow resides, suggests that sluggish blood flow at these sites might facilitate the attachment of metastatic cells. However, slow blood flow alone does not account adequately for metastatic patterns. The high incidence of bone metastases from cancers of the breast and prostate without corresponding lesions in the lung makes it unlikely that malignant cells spreading to bone pass through the pulmonary circulation. Even if lung tissue is not receptive as a site for the establishment of metastatic disease from a particular cancer, tumour cells are still unlikely to pass through its narrow capillaries, particularly when aggregated as tumour emboli. A satisfactory explanation for the predilection of metastatic disease from these cancers to the skeleton has been provided through studies in animals and human cadavers which demonstrated the vertebral-venous plexus of veins [2]. Venous blood from both the pelvis and the breast flows not only into the venae cavae, but also directly into the vertebral-venous plexus. Flow into the vertebral veins predominates when intrathoracic or intra-abdominal pressure is elevated. This work has provided a good explanation for the high frequency with which prostatic and breast cancers, as well as those arising in the kidney, thyroid and lung, produce metastases in the axial skeleton and limb girdles.