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Prostate Cancer Drugs Sap Bone Mass

Chemotherapy may lead to osteoporosis

MONDAY, June 4, 2001 (HealthDayNews) -- Men undergoing "chemical castration" for prostate cancer may pay another price in the form of lost bone density that significantly raises their risk of fractures, says a new study.

The researchers say cancer chemotherapies that block a bone-stimulating hormone can markedly suppress skeletal growth and may lead to osteoporosis.

Because prostate tissue is highly sensitive to testosterone, the male sex hormone, many doctors try to shrink the gland with compounds called gonadotropin-releasing hormone agonists (GnRH-a) which strip the body of testosterone, as well as its sister hormone estrogen.

"It's a very important study," says Dr. David Agus, research director of the Cedars-Sinai Prostate Cancer Center in Los Angeles. "It's very important to recognize the situation because we can remedy it."

Agus says GnRH agonists have become the fallback therapy for many prostate cancer patients who don't respond to initial treatments like surgery or radiation.

GnRH therapy had been used for some time in men with aggressive prostate tumors that have spread to other parts of the body. And lately it has become a common option for trying to prevent the migration of the disease. Prostate cancer occurs in 200,000 American men a year and is the second leading cancer killer of men in this country.

Both testosterone and estrogen, known collectively as androgens, are important in bone formation, and some studies have pointed to an increase in fracture risk among men taking GnRH agonists. Prostate patients who've had their testicles removed to suppress androgen levels are about 16 times more likely to suffer a hip fracture over a seven-year period than those who don't undergo the surgery.

In the latest study, reported in the June issue of the Journal of Clinical Endocrinology and Metabolism, a team led by Dr. Susan Greenspan of the University of Pittsburgh Medical Center compared bone mineral density -- a strong measure of fracture risk -- in 60 men with prostate cancer. Nineteen had received GnRH agonists for at least six months, and 41 never were given the drugs. The researchers also looked at bone mass in 197 healthy men.

Bone scans of the spine, hip, forearm and elsewhere showed the skeletal density in patients taking GnRH agonists was 6 percent to 17 percent lower than those not on the drugs. "We found decreases wherever we looked," says Greenspan, director of Pitt's Osteoporosis Prevention and Treatment Center.

Urine and blood tests also showed signs of bone loss that in some cases were twice as high for men receiving the hormone inhibitors.

The researchers didn't determine how many men had suffered fractures; however, Greenspan says the magnitude of the bone loss, coupled with the natural erosion of skeletal density with age, was enough to cause clinically-defined osteoporosis in at least some patients.

Because patients with prostate cancer aren't likely to stop their therapy to prevent hypothetical fractures, Greenspan says doctors should be aware of the risks of bone breaks in men taking GnRH agonists and advise them about ways to avoid the complication. These include taking calcium and vitamin D supplements and getting plenty of exercise, which has been shown to boost bone strength.

Greenspan is recruiting men for another study to test whether drugs called bisphosphonates, which help prevent bone loss, can overcome the skeletal damage caused by GnRH agonists.

Dr. Pamela Taxel, a University of Connecticut hormone expert who also is examining the impact of GnRH on bone health, says her work shows some men suffer significant losses of bone density from the drugs while others don't. Why that's true isn't clear, though men whose skeletons are stronger to start with may be more protected from the therapy's damage, she says.

Taxel says another puzzle is whether GnRH agonists undermine bone mass by erasing testosterone or whether its impact on estrogen also weakens the skeleton. She says her very preliminary work shows that giving prostate patients small doses of estrogen to counteract GnRH agonists does reduce bone loss.

What To Do

While women make up 80 percent of the 10 million Americans with osteoporosis, doctors increasingly have seen that the condition is gender-blind.

For more on osteoporosis, try the National Osteoporosis Foundation or Endocrine Web. For more on prostate cancer, visit the University of Michigan's Comprehensive Cancer Center.

Read these HealthDay articles about prostate cancer and osteoporosis.

Learn about clinical trials for prostate cancer at Veritas Medicine.

SOURCES: Interviews with Susan Greenspan, M.D., professor of medicine and director, Osteoporosis Prevention and Treatment Center, University of Pittsburgh; Pamela Taxel, M.D., assistant professor of medicine, University of Connecticut School of Medicine, Farmington, and David Agus, M.D., research director, Cedars-Sinai Prostate Cancer Center, Los Angeles; June 2001 Journal of Clinical Endocrinology and Metabolism
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