Fractures linked to androgen deprivation therapy

Treatment used for prostate cancer increased the risk of bone fractures.

Androgen deprivation used to treat prostate cancer increased the risk of bone fractures in older male patients receiving the treatment.

Researchers at the University of Texas Medical Branch studied the effects of androgen deprivation therapy on more than 50,000 men with prostate cancer aged 66 years or older.

“The main finding of the study is that the use of androgen deprivation therapy for prostate cancer is associated with an increased risk of fracture,” Vahakn B. Shahinian, MD, lead researcher and assistant professor of internal medicine at UTMB in Galveston, told Orthopedics Today.

Bone density deteriorates quickly within the first year following androgen deprivation therapy, but previous studies have not thoroughly measured the risk of fracture associated with this type of treatment.

Largest analysis

“This study currently represents the largest analysis to show and quantify the risk of fracture,” said Shahinian.

Researchers collected data on 50,613 men who were diagnosed with prostate cancer between 1992 and 1997 through records on the linked database of the Surveillance, Epidemiology and End Results (SEER) program and Medicare. Patients had to survive at least one year after diagnosis to be included in the study.

The prostate cancer patients were divided into two groups: those who received androgen deprivation therapy and those who did not.

The patients who received androgen deprivation therapy were again divided into groups based on the number of gonadotropin-releasing hormone agonist doses they received in the first year of diagnosis or whether they underwent an orchiectomy.

Researchers examined patient records from the 12 months before diagnosis for bone-related toxic effects. These were compared with the rates of bone-related toxic effects that occurred 12 to 60 months after diagnosis.

Research showed that during the 12 to 60 months following diagnosis, 19.4% of the patients in the androgen deprivation group had a fracture. Only 12.6% of those not receiving treatment had fractures (P<.001).

“Patients who received nine or more doses of a hormone-suppressing drug in the first year of diagnosis developed fractures at a rate of 45% greater than patients who did not receive any form of androgen deprivation,” said Shahinian (RR=1.45; 95% CI, 1.36-1.56).

Patients undergoing orchiectomy had a 54% greater risk of fracture (RR=1.54; 95% CI, 1.42-1.68).

Those receiving androgen deprivation therapy had a higher rate of hospitalization with fracture compared to those not receiving the therapy (5.2% vs. 2.4%; P<.001).

Patients who had nine or more doses of the gonadotropin-releasing hormone agonist in the first year of diagnosis and those who underwent an orchiectomy had the lowest rates of fracture-free survival.

Increased risk

Researchers concluded that androgen deprivation therapy, either in the form of a gonadotropin-releasing hormone agonist or orchiectomy, increased the risk of bone fracture in older male prostate cancer patients.

Shahinian said: “In situations where there is no clear evidence that androgen deprivation prolongs life, the risk of fracture should be taken into account by patients and physicians in risk-benefit discussions about whether to initiate therapy with androgen deprivation.

“For patients in whom androgen deprivation is clearly indicated, bone mineral density should be monitored and therapy with drugs to preserve bone mineral density should be considered.”

For more information:
Shahinian VB, Kuo YF, Freeman JL et al. Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med. 2005; 352:154-164.