Bone mineral density may increase by 6 percent or more after 1 year of bisphosphonate treatment in men who receive the therapy soon after hormone deprivation therapy is initiated and in men who have been on the therapy for a year or longer.
Orlando, FL-The bisphosphonate zoledronic acid (Zometa) should receive primary consideration as a supplement in older patients undergoing androgen deprivation therapy (ADT) following radical prostatectomy or radiation therapy for PSA relapse in prostate cancer. Benefits accrue in almost all men receiving ADT, according to a Veterans Affairs Health Care System study.
Bone mineral density (BMD) may increase by 6% or more after 1 year of treatment with the bisphosphonate. This benefit appears in men who receive the therapy soon after ADT is initiated and also in men who have been on ADT for a year or longer before bisphosphonate therapy is started.
"Prostate cancer is a disease that usually appears in older men. These men are also at increased risk for osteoporosis," said first author Nirmala Bhoopalam, MD, chief of hematology/oncology at the Edward Hines Jr. VA Hospital, Hines, IL. "They are also at risk because of the testosterone deficiency and secondary factors such as ethnicity, age, and lifestyle habits or comorbid conditions or medications."
"Also, men may account for up to 30% of an estimated $17 billion in costs associated with fractures in the U.S.," she told Urology Times.
The placebo-controlled study identified 93 men on ADT following radical prostatectomy and randomized them to placebo or zoledronic acid treatment in one of two strata: men (50) who had been on ADT for less than a year and men (43) who had been on ADT for a year or longer without exposure to the agent. The men (mean age, 70.5 years) were well matched: 55% were Caucasian, 41% were African-American, and 4% were Hispanic.
Dr. Bhoopalam noted that in addition to the elevated fracture risk associated with ADT, a number of these men had other recognized risk factors for osteoporosis, such as a history of smoking, ethanol intake, and other lifestyle factors.
All of the men were started on calcium and vitamin D supplements, and they were advised to engage in weight-bearing exercises and counseled on alcohol moderation and smoking cessation. They were randomized to either intravenous zoledronic acid, 4 mg every 3 months for four treatments, or placebo on the same schedule. BMD was measured by dual energy x-ray absorptiometry (DEXA) scan of the lumbar at baseline and at 6 and 12 months.
Men who began the therapy shortly after embarking on ADT showed a 5.95% increase in spine BMD compared to a 3.23% loss in men given placebo (p=.0044). Those who had been on ADT for 1 year or longer before initiating zoledronic acid treatment showed a 6.08% BMD increase compared to a 1.57% increase in the placebo cohort (p=.005).
"Typically, men on [androgen] deprivation therapy lose about 4% of BMD during the first year of therapy and perhaps 2% per year thereafter. As BMD decreases, the risk of fracture increases," Dr. Bhoopalam said, adding that there is more to the therapy than offering infusions every 3 months.
"Vitamin D and calcium supplements are recommended for all patients. It is VA hospital policy that all patients about to go on ADT be counseled on lifestyle modifications, such as smoking cessation and alcohol moderation. All patients get a preventive dental evaluation to ensure they have no caries. They also have a baseline DEXA scan.
"We don't usually start them on zoledronic acid right away, but stratify them according to risks. We conduct annual DEXA scans and initiate zoledronic acid when BMD starts to decline."
The study shows that zoledronic acid can work well in high-risk populations, and works even when started later in the course of ADT, she concluded.
"We had a hunch this would work because of cancer studies in women and in others, but until now, we had not known how the therapy would affect these men."