Effects of the bisphosphonate olpadronate in patients with carcinoma of the prostate metastatic to the skeleton.

Prostate cancer is predominantly associated with osteoblastic bone metastases, but an increase in bone resorption has been demonstrated consistently, both histologically and biochemically. For this reason, bisphosphonates, which effectively suppress bone resorption, have been used in patients with prostate cancer metastatic to the skeleton. We studied clinical and biochemical responses 5 days and 3 months after administration of the new, potent bisphosphonate, olpadronate, in 28 patients with prostate cancer and bone metastases. All patients received 4 mg of olpadronate intravenously daily for 5 days. No additional treatment was given to the first 12 patients, while treatment was continued with oral olpadronate 200 mg daily in the following 16 patients. Serum alkaline phosphatase (ALP) activity was elevated in 93% of the patients and was positively correlated to urinary hydroxyproline excretion (r = 0.81, p < 0.0001), suggesting a coupling between bone formation and resorption. A rapid and significant suppression of bone resorption was observed in all patients after intravenous treatment. This was sustained for 4-6 weeks in all patients, but reversed thereafter in patients not receiving oral maintenance therapy. No significant changes in serum ALP activity were observed in either group during the 3 months of follow-up. At the start of treatment all patients had severe bone pain and 82% and 36% were using NSAIDs and/or opiates, respectively. Although clinical response was not a primary objective of the study, we observed that intravenous therapy was associated with a decrease in bone pain in 76% of patients and a reduction in the use of analgesics. At 3 months this response was generally sustained only in those patients who were maintained on continuous oral therapy (p < 0.05 compared with the group treated with intravenous olpadronate only). The clinical response thus appeared to parallel the biochemical changes in bone resorption.