Zoledronic Acid Reduces Mortality After Hip Fracture: Presented at ASBMR

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Title: Zoledronic Acid Reduces Mortality After Hip Fracture: Presented at ASBMR
URL: http://www.pslgroup.com/dg/22C5EA.htm
Doctor's Guide
September 15, 2008

By Louise Gagnon

MONTREAL -- September 15, 2008 -- Therapy with zoledronic acid subsequent to a hip fracture decreases the patient's high mortality risk, particularly for cardiovascular disease and infections, according to research presented here at the American Society for Bone and Mineral Research (ASBMR) 30th Annual Meeting.

Hip fractures are associated with 1-year mortality rates of between 18% and 30%, but the administration of zoledronic acid in this population resulted in a substantial 28% reduction in mortality risk after 1 year compared to placebo, noted principal investigator Cathleen Colon-Emeric, MD, MHc, Duke University Medical Center, Durham, North Carolina, and Durham Veterans' Affairs Geriatrics Research Education and Clinical Center, Durham.

Dr. Colon-Emeric presented results from the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Recurrent Fracture Trial (HORIZON-RFT) in an oral session here on September 13. The retrospective analysis examined 2,111 patients who received at least 1 dose of the study drug.

"Because of zoledronic acid's impact on immunomodulatory factors, cytokines, and tumour necrosis factor, we hypothesised that that there might be an effect on infections, on cardiovascular disease, and on malignancies," said Dr. Colon-Emeric in an interview during the session.

She and her co-investigators analysed data from the HORIZON-RFT database and found similar incidences in infection, cardiovascular illness, and cancer in patients who received either a placebo or zoledronic acid. There was, however, a decreased risk of mortality from those illnesses when patients were treated with zoledronic acid compared to placebo (with the exception of stroke).

In a risk model that examined mortality due to common conditions, the researchers found that zoledronic acid decreased the risk of mortality by 25%. When the investigators took subsequent fractures into account, they were significantly associated with an elevated risk of mortality (hazard ratio = 1.72; 95% confidence interval, 1.17-2.51). The increased risk, however, explained only 2% more of the impact of zoledronic acid.

"The data suggest that [the] chance of dying of those illnesses [pneumonia, neoplasms, cardiovascular disease] was much less if you were taking zoledronic acid compared to placebo," said Dr. Colon-Emeric.

The results of this analysis should prompt further immunomodulatory investigations, Dr. Colon-Emeric concluded, examining the modifications in cytokines and inflammatory markers that are being exposed to therapies like zoledronic acid, and determining what the effect is on cardiovascular disease, infections, and, perhaps, even frailty.

Funding for this study was provided by Novartis Pharma AG.

Presentation title: Potential Mediators of the Reduction in Mortality With Zoledronic Acid After Hip Fracture. Abstract 1030]

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