Zoledronic acid may have role other than fracture reduction

Zoledronic acid reduced the risk for death by 25% in patients with hip fracture, but only 8% of the bisphosphonate’s death benefit was attributed to reduction in secondary fractures, according to the results of a retrospective analysis of a randomized, controlled trial.

Zoledronic acid (Reclast, Novartis) may also have an effect on cardiovascular events and pneumonia, researchers concluded.

The study included 2,111 patients with recent hip fracture randomly assigned to yearly zoledronic acid or placebo injection and calcium and vitamin D supplementation. Multivariate analysis included baseline co-morbidities such as, subsequent fractures, changes in bone mineral density, infections, CV events, arrhythmia and falls.

In the current retrospective analysis, zoledronic acid reduced the risk for fracture by 25% (95% CI, 0.58-0.97) — the effect was consistent across most subgroups. In addition, zoledronic acid accounted for only 8% of subsequent fractures associated with death (HR=1.72; 95% CI, 1.17-2.51).

After adjustment for acute events that occurred during follow-up, patients treated with zoledronic acid were less likely to die from arrhythmias (P=.02) and pneumonia (P=.04) when compared with placebo.

According to data published in 2007, patients who received zoledronic acid injection within 90 days of hip fracture surgery had a 28% reduction in mortality. Further, patients assigned zoledronic acid were 35% less likely to have another fracture compared with patients assigned placebo.

The researchers concluded that “further studies of zoledronic acid in other acute illnesses may be warranted.” – by Jennifer Southall

Colon-Emeric C. J Bone Miner Res. 2009.

Since studies have shown that there is a significant increase in mortality after fractures it is not surprising that there was a decrease in mortality after zoledronic acid. However, it is surprising that the decrease in mortality was only slightly related to a reduction in fractures. A meta-analysis of mortality in the previous numerous controlled trials of zoledronic acid would be of interest. It is not at all apparent at this time why zoledronic acid would significantly reduce mortality based on any factor except fracture prevention.

Fred R. Singer, MD

Director, Endocrine/Bone Disease Program, John Wayne Cancer Institute at Saint John's Health Center, California