The Effects of Orchidectomy on Skeletal Metabolism in Metastatic Prostate Cancer

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Abstract
The skeletal metabolic effects of androgen withdrawal have been studied in men with metastatic prostate cancer by using a combination of sequential biochemical measurement, quantitative and subjective bone histology and selective osteoclast inhibition with the bisphosphonate Pamidronate. Results showed dissociation in the levels of biochemical markers of bone formation (alkaline phosphatase and osteocalcin) following castration, whilst markers of bone breakdown (urinary hydroxyproline creatinine (OHP) and calcium excretion (CaE)) increased in the majority of patients. The osteolytic response was inhibited by the bisphosphonate Pamidronate (Aminohydroxypropylidene Bisphosphonate (APD)), thus confirming its osteoclastic origin. Histomorphometry of tumour free bone showed an acute drop in bone volume following surgery (p < 0.05). This effect was blocked by Pamidronate suggesting that osteoclastic activity surges immediately following castration, contributing to the acute bone loss. Histology of metastatic areas showed a marked diminution in bone volume due to decreased osteoblast activity and markedly increased osteoclast mediated osteolysis. In 56% of biopsies there were residual foci of active tumour within metastatic areas after orchidectomy. These disturbed metabolic bone activity in a typically localised manner.