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Androgen-deprivation therapy for prostate cancer increases the risk of fracture among elderly men

The use of androgen-deprivation therapy for prostate cancer has increased substantially over the past 15 years. This therapy has been associated with a loss of bone mineral density. It also increases an elderly man's risk of bone fracture, according to a study supported in part by the Agency for Healthcare Research and Quality (HS11618). This finding underscores the need for caution in the use of these therapies in settings without clear evidence of benefit, notes Jean L. Freeman, Ph.D, of the University of Texas Medical Branch.

Dr. Freeman and her colleagues linked the database of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program with Medicare files to assess the risk of fracture associated with androgen deprivation in the form of orchiectomy (surgical removal of one or both testicles) or treatment with gonadotropin-releasing hormone agonists. They studied two groups of men aged 66 and older who were diagnosed with prostate cancer from 1992 through 1997: an androgen-deprivation group and a control (non-treatment) group.

Among men who survived at least 5 years after diagnosis, 19.4 percent of those in the androgen-deprivation group had a fracture compared with 12.7 percent of those not receiving the treatment. Also, 5.2 percent of those treated with androgen-deprivation therapy were hospitalized with a fracture compared with 2.4 percent of those not treated.

The relative risk of any fracture and fractures requiring hospitalization was 1.45 and 1.66, respectively, among those receiving nine or more doses of gonadotropin-releasing hormone agonist in the first 12 months following diagnosis and 1.54 and 1.70, respectively, among those who underwent orchiectomy. The researchers calculated that about 3,000 excess fractures per year could be attributable to the use of gonadotropin-releasing hormone agonists, even after adjustment for known confounding factors and preexisting bone disease.

More details are in "Risk of fracture after androgen deprivation for prostate cancer," by Vahakn B. Shahinian M.D., Yong-Fang Kuo, Ph.D., Dr. Freeman, and James S. Goodwin, M.D., in the January 13, 2005, New England Journal of Medicine 352(2), pp. 154-164.

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