Peter McCallum Cancer Institute, Victoria 8006, Australia
Address correspondence to: Robin Murray, M.D., Peter McCallum Cancer Institute, Locked Bag 1, ABeckett Street, Victoria 8006, Australia.
To the editor:
We agree with Dr. Berruti and colleagues that there is increasing evidence of increased bone resorption in prostate cancer patients with bone metastases. The cause of this would seem to be multifactorial, involving production of local factors from tumor cells that stimulate osteoclasts and, in castrate patients, increased bone resorption secondary to loss of sex steroid. In addition, PTH is known to be a potent stimulator of osteoclastic activity. Because Dr. Berruti and colleagues have shown that a single dose of pamidronate in patients with advanced prostate cancer is associated with a subsequent fall in urinary markers of bone breakdown, they believe that our postulate that the use of bisphosphonates in patients with hypocalcemia and/or hyperparathyroidism might lead to further hypocalcemia and increased hyperparathyroidism is questionable. However, in their study it is not clear whether the effects of pamidronate occur on sites distant from metastases, or at the site of metastases or both. Clarke et al. (1) have reported that in patients with advanced prostate cancer low-dose pamidronate repeated weekly for 4 wk, then twice monthly for 5 months restored abnormal levels of bone erosion in tumor-free areas to normal in 93% of cases. Suppression of bone destruction was also evident within metastases, although this was incomplete. Thus, in these areas where osteoclastic activity was still occurring, high levels of PTH may continue to be one of the factors involved in increased bone resorption.
Dr. Berruti and colleagues also report a case of a patient treated with 60 mg pamidronate every 3 wk for a total of four times in whom high pretreatment levels of PTH returned to normal. It is, therefore, of interest that in a recent trial of zoledronic acid vs. placebo in patients with bone metastases from prostate cancer, PTH levels increased by an average of more than 60% over a 9-month period in the zoledronic acid group despite calcium and vitamin D supplements (2).
We agree with Dr. Berruti that additional studies are necessary to define the relationship between the efficacy of bisphosphonates and PTH levels in these patients.
Received January 12, 2002.
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