Use of markers of bone turnover for monitoring bone metastases and the response to therapy

Metastatic bone disease is a frequent complication of breast and other cancers, resulting in skeletal complications that are a significant cause of morbidity and mortality. Bone metastases can be difficult to diagnose radiologically and it can also be difficult to evaluate patients' response to treatment by using the methods that are currently available (radiography, bone scans, and computed axial tomography scans). These are relatively insensitive procedures, thus, there is a requirement for new methods for assessing bone response to ensure patients benefit from the optimum type and duration of treatment. Biochemical markers of bone turnover, such as N-telopeptide and the pyridinium cross-links pyridinoline and deoxypyridinoline, may provide information on bone dynamics that in turn may reflect disease activity in bone. Several studies have shown bone markers to be elevated in cancer patients who have documented evidence of metastatic bone disease. Increased levels are also observed in some patients without clinical evidence of bone metastases, when compared with normal subjects. Rises in such markers may be the first indication of bone involvement and therefore may potentially be useful in early diagnosis of progression. Preliminary data suggest bone marker level correlates with the extent of metastatic disease and the number of skeletal sites involved. Markers of bone turnover may be helpful in identifying those patients likely to respond to bisphosphonate treatment. Such markers are also potentially useful in monitoring the effectiveness of bisphosphonate therapy in the management of bone metastases, in both patients with metastatic breast disease and multiple myeloma.