Trial Information

Prevention of Osteoporosis in Men With Prostate Cancer

Prostate cancer is the most common visceral malignancy and second leading cause of cancer
death in men. While androgen ablation therapy is the cornerstone of treatment for more
advanced stage disease, recent studies suggest the advantage of introducing androgen
deprivation much earlier. Because androgens are essential in maintaining skeletal integrity
in men, androgen deprivation therapy constitutes a major risk factor for male osteoporosis.
We have previously demonstrated that men on chronic androgen deprivation therapy have up to
20% loss of bone. Our hypotheses are that: 1) chronically increased bone resorption induced
by long term androgen deprivation therapy in men with prostate cancer can be reversed with
once weekly bisphosphonate; 2) the improvement in bone mass with bisphosphonate therapy will
be reflected by changes in biochemical markers of bone turnover and will allow us to predict
who will respond to therapy; and 3) following termination of bisphosphonate therapy, bone
mass will be maintained despite the absence of antiresorptive therapy. To address these
hypotheses, we will enroll 84 men with stage D0 prostate cancer who have been on chronic
androgen deprivation therapy in a two year, double blind, placebo controlled, randomized,
modified crossover clinical design. During the first year, subjects will be randomized to
bisphosphonate therapy or placebo. During the second year, all subjects who were on placebo
will receive active treatment and all subjects who were on active treatment will be randomly
assigned to continue therapy or change to placebo. To evaluate the effect of bisphosphonate
on preventing bone loss, we will assess bone mass of the spine, total hip, total body, and
forearm by dual-energy X-ray absorptiometry. For hypothesis 2, we will assess markers of
bone resorption and formation to determine if early changes in markers are associated with
long term changes in bone mass. For hypothesis 3, we will continue to follow bone mass and
biochemical markers of bone turnover between months 12 and 24 to examine rates of change
when antiresorptive therapy is terminated. Few data are available on the prevention of bone
loss in men on androgen deprivation therapy. This study will examine a preventive strategy,
the potential mechanism of bone loss, the ability of biochemical markers to predict bone
mass, and skeletal outcomes when antiresorptive therapy is withdrawn.