Drug Can Slow Bone Loss in Prostate Cancer Patients

By Alan Mozes
20 sept 2008-- Men receiving hormone-deprivation therapy for advanced but localized prostate cancer can develop bone loss as a side effect of the treatment.
But a new study finds that bone-strengthening drugs such as Fosamax (generic name alendronate) can help prevent that damage.
Having earlier found that alendronate successfully prevents bone loss for patients on hormone-depletion therapy after just one year, the current follow-up reveals that two years of the drug affords men even greater protection.
"The population is aging rapidly, and with it comes the increased risk of age-related disease, one of the most common of which for men being prostate cancer," noted study co-author Dr. Neil M. Resnick, a professor of medicine in the department of geriatrics at the University of Pittsburgh.
Because testosterone is thought to spur prostate cancer, patients typically are placed on an androgen-deprivation therapy (ADT). "The good news is that ADT therapy works," Resnick said.
"However, one of the predicaments doctors and patients have had to deal with is the side effect of osteoporosis resulting from the drug's blocking of the body's ability to generate androgens, the most common of which is testosterone," explained Resnick. "Blocking this suppresses tumor growth and helps the patient live longer, but bones require testosterone to remain strong, so depleting it can raise the risk for osteoporosis. And now, we have data to show that if doctors add this common medication -- alendronate -- early enough, and for two years, they can substantially decrease that risk."
The authors pointed out that ADT use has increased two- to fourfold over the past decade. Therapy-associated bone loss is greatest within the first year of treatment, and chronic long-term ADT has been linked to a doubling or quadrupling of men's fracture risk.
Resnick and his colleagues reported on their findings in the Sept. 20 issue of the Journal of Clinical Oncology.
According to Fosamax's maker, Merck & Co. Inc., the drug is designed to impede specific cell activities that contribute to bone loss, while increasing bone mass itself and decreasing the relatively speedy rate of loss associated with both menopause and corticosteroid medications. The drug also became available in a generic form earlier this year.
The new study involved 112 men under the age of 85, who were diagnosed with advanced but non-metastatic prostate cancer. They tracked the men's bone health for a total of two years.
In the first year, half of the men were randomly assigned to receive 70 milligrams of alendronate once a week, while the other half received a placebo. For the second year, half of those who had taken alendronate the first year were switched to a placebo, while the other half continued taking the medication. The initial placebo group was, in turn, switched to a regimen of alendronate.
The authors then conducted an analysis of bone mineral density, bone loss and bone gain among all the patients. In particular, they assessed what effect the discontinuation of alendronate therapy after a year had upon patients.
Men who took alendronate the full two years continued to add bone density in their spinal and hip regions, the researchers reported.
Those taken off the medication retained gains they'd achieved in those areas but lost some bone density in the forearm region.
Patients just beginning alendronate treatment for the first time in the second year of the study saw bone mass improvements in both the spinal and hip area but experienced less of a gain than those who had begun the treatment in the first year. Discontinuation of the treatment in the second year resulted in some bone loss and skeletal deterioration, the researchers reported.
Based on the findings, the team advised that alendronate treatment be prescribed for prostate cancer patients at the same time ADT is commenced.
Dr. Matthew Smith, director of genitourinary medical oncology at Massachusetts General Hospital Cancer Center, Boston, said that while the current study is "beautiful work," more focused research is needed, given that fracture risk is an "underappreciated problem."
"There have already been a number of studies looking at drugs to increase bone density," Smith said. "So this is not a criticism of this study, but I have to say that, really, what we need now are large long-term studies that look at how to prevent fractures in men. We want high-level evidence for any intervention that we do, and we haven't had that so far."