THE EFFECTS OF ORCHIECTOMY ON SKELETAL METABOLISM IN METASTATIC PROSTATE-CANCER

The skeletal metabolic effects of androgen withdrawal have been studie d in men with metastatic prostate cancer by using a combination of seq uential biochemical measurement, quantitative and subjective bone hist ology and selective osteoclast inhibition with the bisphosphonate Pami dronate. Results showed dissociation in the levels of biochemical mark ers of bone formation (alkaline phosphatase and osteocalcin) following castration, whilst markers of bone breakdown (urinary hydroxyproline creatinine (OHP) and calcium excretion (Ca-E)) increased in the majori ty of patients. The osteolytic response was inhibited by the bisphosph onate Pamidronate (Aminohydroxypropylidene Bisphosphonate (APD)), thus confirming its osteoclastic origin. Histomorphometry of tumour free b one showed an acute drop in bone volume following surgery (p < 0.05). This effect was blocked by Pamidronate suggesting that osteoclastic ac tivity surges immediately following castration, contributing to the ac ute bone loss. Histology of metastatic areas showed a marked diminutio n in bone volume due to decreased osteoblast activity and markedly inc reased osteoclast mediated osteolysis. In 56% of biopsies there were r esidual foci of active tumour within metastatic areas after orchidecto my. These disturbed metabolic bone activity in a typically localised m anner.