Uses and abuses of bisphosphonates.

The skeleton is the most common organ to be affected by metastatic breast cancer, and the site of disease which produces the greatest morbidity. Skeletal morbidity includes pain requiring radiotherapy, hypercalcaemia, pathological fracture, and spinal cord or nerve root compression. From randomised trials in advanced breast cancer [1,2] it can be seen that one of these major skeletal events occurs on average every 3-4 months. Additionally, metastatic disease may remain confined to the skeleton with the decline in quality of life and eventual death due entirely to skeletal complications. There is now a much greater understanding of the mechanisms underlying the development of bone metastases and the interdependence between cancer cells and bone. Tumour cells within the bone marrow cavity secrete a variety of paracrine factors that stimulate bone cell function. This stimulation of osteoclast function is of particular importance, resulting in osteolysis which is typically associated with disruption of the normal coupling signals between osteoblast and osteoclast function, and is the rationale for the use of bisphosphonates in the management of metastatic bone disease. These effects on bone cell function may in rum influence serum and urinary levels of biochemical markers of bone metabolism which may be used to monitor the progress of the disease and response to treatment.