Hormonal Blockade For Prostate Cancer May Cause Rapid Severe Bone Loss

PITTSBURGH /PSA Rising/, June 5 -- Men may be losing bone at an alarming rate as a result of a commonly used treatment for prostate cancer, according to researchers at the University of Pittsburgh Medical Center (UPMC) and Beth Israel Deaconess Medical Center. The findings, published in the June issue of the Journal of Clinical Endocrinology and Metabolism, suggest that gonadotropin-releasing hormone agonists (GnRH-a), a frequently used treatment for prostate cancer, causes severe drops in bone mass and results in an increased risk of fracture in men.

"We were surprised to find that men who were treated with GnRH-a for prostate cancer experienced up to a decade's worth of bone loss within the first year of therapy," said senior author Susan Greenspan, M.D., professor, divisions of endocrinology and geriatric medicine, department of medicine, University of Pittsburgh; and director, Osteoporosis Prevention and Treatment Center, UPMC.

GnRH-a works by depriving the body of testosterone, an androgen hormone that increases the growth of prostate tumors. However, testosterone also is essential to maintaining bone mass in men. While doctors have been using GnRH-a for more than a decade in treating men with late-stage metastatic prostate cancer, they have begun using it more recently in men with earlier-stage disease and for longer periods of time.

"In treating men with this therapy earlier and for longer periods of time, we are putting them in a menopause-equivalent condition and subjecting them to severe osteoporosis -- a disease that may have more serious consequences than early-stage prostate cancer," said Dr. Greenspan. "With close to 200,000 men being diagnosed with prostate cancer each year, we could be facing an enormous increase in the incidence of debilitating bone fractures in men."

In this study, investigators compared bone mineral densities (BMD), biochemical markers of bone turnover and body composition in 60 men with prostate cancer -- 19 of whom were on GnRH-a and 41 who were not -- and BMD in 197 healthy men.

While the prostate cancer patients who had not been treated with GnRH-a had BMDs that were similar to those of the healthy controls, the scores of men treated with GnRH-a showed dramatically different results in several categories.

The treated men had BMD levels that were up to 17 percent lower than those of untreated men, putting the treated men at a markedly higher risk for fracture. Treated men also had nearly double the levels of urinary NTx, a marker for bone resorption, indicating that their bones were disintegrating twice as quickly as the bones of untreated men. In addition, they had significantly lower blood counts and levels of estradiol, a hormone that is needed, along with testosterone, for bone health. Treated men also showed an increase in total body fat and loss of muscle mass.

"Clearly, cutting off testosterone production in men through the administration of GnRH-a has some very serious consequences related to skeletal integrity and overall health," continued Dr. Greenspan. "This is particularly troubling because the greatest degree of bone loss appears to occur with the initiation of treatment."

Among others now looking for ways to avoid bone loss of hormonal blockade for prostate cancer, researchers at University of California San Francisco have looked to see if PC-SPES's estrogen content might protect bone integrity.

"Bone mineral density loss is a concerning side effect of androgen deprivation therapy," says Dr. Eric Small, in a paper published May 12 in the Proceedings of the American Society of Clinical Oncology (ASCO). This common side effect of Lupron, Zoladex and other testosterone-blocking drugs for prostate cancer can lead to crippling fractures of spine and/or hip.

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To find out if you are at risk for bone mineral density loss, get a bone density scan (DEXA scan). To find out what drugs are available and effective to protect your bone integrity, consult a board certified endocrinologist or bone specialist. Many patients report that because of a bias toward seeing osteoporosis as a disease of post-menopausal women and biphosphonates as treatment for lytic bone lesions (of e.g. breast cancer), urological and clinical oncologists deny this problem. --ed.

Dr. Greenspan is currently recruiting patients for a study to determine whether bisphosphonate, an anti-resorptive therapy, can prevent or abate bone loss in men who are being treated with GnRH-a for prostate cancer. For more information about participating in this study, please call the UPMC Osteoporosis Prevention and Treatment Center at 412-692-2220.

LINKS

Bisphosphonate treatment inhibits the growth of prostate cancer cells. Lee MV, et al. Cancer Res. 2001 Mar 15;61(6):2602-8.

Osteoporos Int 2001;12(2):112-6 Intravenous pamidronate as treatment for osteoporosis after heart transplantation: a prospective study. Krieg MA, Seydoux C, Sandini L, Goy JJ, Berguer DG, Thiebaud D, Burckhardt P. Department of Internal Medicine, Service A, University Hospital, Lausanne, Switzerland.