Clinical Features of Metastatic Bone Disease and Risk of Skeletal Morbidity

Abstract

The skeleton is the most common organ to be affected by metastatic cancer and the site of disease that produces the greatest morbidity. Skeletal morbidity includes pain that requires radiotherapy, hypercalcemia, pathologic fracture, and spinal cord or nerve root compression. From randomized trials in advanced cancer, it can be seen that one of these major skeletal events occurs on average every 3 to 6 months. Additionally, metastatic disease may remain confined to the skeleton with the decline in quality of life and eventual death almost entirely due to skeletal complications and their treatment. The prognosis of metastatic bone disease is dependent on the primary site, with breast and prostate cancers associated with a survival measured in years compared with lung cancer, where the average survival is only a matter of months. Additionally, the presence of extraosseous disease and the extent and tempo of the bone disease are powerful predictors of outcome. The latter is best estimated by measurement of bone-specific markers, and recent studies have shown a strong correlation between the rate of bone resorption and clinical outcome, both in terms of skeletal morbidity and progression of the underlying disease or death. Our improved understanding of prognostic and predictive factors may enable delivery of a more personalized treatment for the individual patient and a more cost-effective use of health care resources. Incidence of Bone MetastasesBone is the most common site for metastasis in cancer and is of particular clinical importance in breast and prostate cancers because of the prevalence of these diseases. At postmortem examination, f70% of patients dying of these cancers have evidence of metastatic bone disease (Table 1; ref. 1). However, bone metastases may complicate a wide range of malignancies, resulting in considerable morbidity and complex demands on health care resources. Carcinomas of the thyroid, kidney, and bronchus also commonly give rise to bone metastases, with an incidence at postmortem examination of 30% to 40%. However, tumors of the gastrointestinal tract rarely (<10%) produce bone metastases. Distribution of Bone MetastasesBone metastases most commonly affect the axial skeleton. The axial skeleton contains the red marrow in the adult, which suggests that properties of the circulation, cells, and extracellular matrix within this region could assist in the formation of bone metastases. Evidence exists that blood from some anatomic sites may drain directly into the axial skeleton. In postmortem studies of animals and humans, Batson (2) showed that venous blood from the breasts and pelvis flowed not only into the venae cavae but also into a vertebral-venous plexus of vessels that extended from the pelvis throughout the epidural and perivertebral veins. The drainage of blood to the skeleton via the vertebral-venous plexus may, at least in part, explain the tendency of breast and prostate cancers, as well as those arising in kidney, thyroid, and lung, to produce metastases in the axial s...

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