Medication prevents osteoporosis in men treated for prostate cancer

Osteoporosis is typically thought of as a problem of older women, but the bone-thinning condition also affects men. One of the fastest-growing osteoporosis risk groups consists of men with prostate cancer who receive androgen-deprivation therapy to lower testosterone levels. In the Sept. 27 issue of New England Journal of Medicine, researchers from the Massachusetts General Hospital (MGH) describe how the drug pamidronate prevented bone loss in prostate cancer patients treated with what are called GnRH agonists.

It is well known that testosterone and other male hormones called androgens stimulate the growth of prostate cancer. As a result, treatments that suppress levels of such hormones have become a mainstay of treatment for advanced prostate cancer. GnRH (gonadotropin-releasing hormone) agonists, which lower testosterone levels, have been so successful in improving treatment of metastatic cancer that they now are commonly used earlier in the course of the disease, making understanding and treating any side effects more important. And osteoporosis is among these drugs? most significant side effects.

Matthew R. Smith, MD, PhD, an MGH oncologist who is the study?s first author, notes, "Most men with advanced prostate cancer suffer serious skeletal complications, which can be exacerbated by osteoporosis. The expanding use of hormone-blocking therapies, with some patients staying on them for years, means that the problem of bone loss is becoming crucial."

MGH endocrinologist Joel Finkelstein, MD, the study?s senior author agrees. "The problems of bone loss and fracture due to hormonal suppression therapy for prostate cancer are often not appreciated by clinicians. As men with prostate cancer receive these therapies earlier in the course of their disease and for longer periods of time, these problems are bound to increase."

The study enrolled 47 prostate cancer patients who received intravenous treatments containing either only the drug leuprolide, a GnRH agonist, or leuprolide plus pamidronate, a drug that stops the breakdown of bone and is used to treat several bone diseases. After the 48-week study period, there were significant differences in bone mineral density between the two groups: those receiving leuprolide alone had bone loss at various sites ranging from 2 to 8 percent, while the men who also received pamidronate had no significant changes in bone density.

"This is the first study to show a safe and effective way to prevent bone loss among men on androgen-deprivation therapy," says Smith. "The high rates of bone loss seen in the control group highlight the real risk of osteoporosis for these patients."

The researchers note that future studies are required to refine potential treatment strategies. "We need both to determine the dosages and treatment intervals of pamidronate that are most effective and to investigate whether other osteoporosis treatments, including those that can be administered orally, can also be helpful for these patients," says Finkelstein.

The study's co-authors are Francis McGovern, MD, Anthony Zeitman, MD, Mary Anne Fallon, LPN, Douglas Hayden, MA, and David Schoenfeld, PhD, of the MGH and Philip Kantoff, MD, of Dana Farber Cancer Institute. The research was supported by grants from the National Institutes of Health, CaP CURE, Novartis Oncology (which manufactures pamidronate) and the Doris Duke Charitable Foundation.

The Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of almost $300 million and major research centers in AIDS, the neurosciences, cardiovascular research, cancer, cutaneous biology, transplantation biology and photomedicine. In 1994, the MGH joined with Brigham and Women's Hospital to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups and nonacute and home health services.