Disodium pamidronate identifies differential osteoclastic bone resorption in metastatic prostate cancer

Abstract

In a controlled trial the effects of the osteoclast inhibitor disodium pamidronate were studied over a 6-month period in men with metastatic bone disease from prostate cancer. Using serial biochemical measurement of metabolic bone activity, and complementary subjective and quantitative bone histology, the effects of pamidronate were evaluated in tumour-free and metastatic regions of the skeleton, enabling analysis of the differential mechanisms of bone destruction in this disease. Following treatment, abnormally high markers of bone breakdown fell significantly (fasting urine hydroxyproline/creatinine (OHP): P less than 0.05; fasting urine calcium excretion (CaE): P less than 0.0001), confirming that activated osteoclasts play an integral role in the osteolytic process. Serial histomorphometry of bone from tumour-free areas showed that pamidronate restored abnormal levels of bone erosion to normal in 93% of cases. Suppression of bone destruction was also evident within metastases, although this was incomplete. The results confirm that osteoclast overactivity is responsible for a significant proportion of the accelerated osteolysis seen in both tumour-free and infiltrated bone in patients with prostate cancer. The differential effects in tumour-free and infiltrated bone suggest that the mechanisms of osteoclast activation may differ in metastatic and non-metastatic regions of the skeleton.