In androgen-deprived prostate CA, zoledronic acid helps BMD even if started late

NEW YORK (Reuters Health) - Zoledronic acid improves bone mineral density (BMD) in prostate cancer patients on androgen deprivation therapy (ADT) even when started more than a year later, a study in the November issue of The Journal of Urology suggests.

Previous research pointed to the value of timing bisphosphonates with the start of ADT.

Bisphosphonates like zoledronic acid are widely used for metastatic prostate cancer, helping control bone lesion pain, normalize serum calcium and prevent pathologic fractures. Though recent studies found good efficacy for using bisphosphonates to prevent osteoporosis in patients on ADT, Dr. Nirmala Bhoompalam, of Loyola University of Chicago, thinks many patients get zoledronic acid unnecessarily, she told Reuters Health.

"We know they are going to become osteopenic or osteoporotic, but at what point do we really need to start them on bisphosphonate therapy?" Dr. Bhoompalam asked.

Along with colleagues at 11 Veterans Affairs medical centers, Dr. Bhoompalam enrolled 93 patients with M0 prostate cancer who were either scheduled to start ADT soon or who had been on ADT for at least a year. The double-blind trial randomized both strata of patients into treatment and control groups with and without zoledronic acid. The experimental arm received 4 mg of intravenous zoledronic acid every three months for the year-long study period.

While many patients had extensive risk factors for osteoporosis, including sedentary lifestyles, low use of calcium or vitamin D supplements, and alcohol and tobacco histories, they did not yet have osteoporosis or osteopenia as measured by T scores. All patients received calcium and vitamin D supplements in the study protocol, along with advice about lifestyle habits and the importance of regular weight bearing exercise.

Investigators obtained dual energy x-ray absorptiometry (DEXA) scans of the lumbar spine and hips at enrollment, month 6, and at the end of the 12-month study. Lumbar spine BMD was the primary outcome measure.

Among patients who started ADT and zoledronic acid (or placebo) at the same time, BMD increased 5.12% on the bisphosphonate and decreased 3.13% without it (p=0.0029). Even among patients who had already been receiving ADT for more than a year, BMD improved 4.82% with zoledronic acid versus a 0.99% increase in the placebo group (p=0.0013).

The study authors believe that their universal provision of lifestyle and exercise advice along with calcium and vitamin D supplementation led to BMD improvement in the controls. They observed significant but smaller BMD increases in the hips in both groups.

Zoledronic acid was associated with rare adverse events including musculoskeletal pain and hypocalcemia in 4 patients. There were no cases of osteonecrosis of the jaw.

BMD is a surrogate indicator of fracture risk, so the investigators are planning to follow this cohort longitudinally to measure that outcome. "What is the long term effect of bisphosphonate therapy on the progression of the disease? We don't know that," said Dr. Bhoompalam.

In the VA system, each zoledronic acid infusion costs about $720, the authors note. Dr. Bhoompalam suggested to Reuters Health that evidence may eventually support following patients with serial DEXA scans to determine when a patient on ADT is becoming osteoporotic or osteopenic, and then starting zoledronic acid therapy.

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