Agent increases BMD in men on GnRH agonists; may raise risk of renal impairment

In prostate cancer patients receiving a gonadotropin-releasing hormone agonist, a single treatment with the bisphosphonate zoledronic acid (Zometa) significantly increases bone mineral density, according to researchers at Massachusetts General Hospital and Dana-Farber Cancer Institute, Boston.

In the 12-month study, which is published in the Journal of Clinical Oncology (2007; 25:1038-42), 40 men with nonmetastatic prostate cancer who were receiving a GnRH agonist and had T scores more than –2.5 were randomly assigned to zoledronic acid, 4 mg intravenously on day 1 only, or placebo. Bone mineral density of the posteroanterior lumbar spine and proximal femur were measured by dual-energy x-ray absorptiometry.

Mean bone mineral density of the posteroanterior lumbar spine decreased by 3.1% ±1% in men assigned to placebo and increased by 4.0% ±1% in men assigned to zoledronic acid (p<.001). Bone mineral density of the total hip decreased by 1.9% ±0.7% in men assigned to placebo and increased by 0.7% ±0.5% in men assigned to zoledronic acid (p=.004). Similar between-group differences were observed for the femoral neck and trochanter. Serum N-telopeptide, a marker of osteoclast activity, decreased significantly after zoledronic acid treatment, reported the authors, led by Matthew R. Smith, MD, PhD.

The study was supported in part by a research award from Novartis Oncology.

In a separate study, Dana-Farber researchers found that, in an outpatient clinic setting, the risk of renal impairment among patients with hormone-refractory prostate cancer who received zoledronic acid was greater than the risk reported previously in clinical trials (Cancer 2007; 109:1090-6).

The authors conducted a comprehensive medical records review and assessed the risk of renal impairment in 122 patients with hormone-refractory prostate cancer who received zoledronic acid from December 1999 to April 2005.

Renal impairment was observed in 23.8% of patients. The risk of renal impairment increased with an extended duration of zoledronic acid therapy (<6 months, 11.1%; ≥24 months, 26.3%) and previous treatment with pamidronate (Aredia) (45.5% vs. 19.0% for patients with no prior pamidronate). A significantly greater risk of renal impairment was associated with increasing age at zoledronic acid initiation, prior pamidronate use, and a history of renal disease, hypertension, or smoking (p ≤.05).