HONOLULU, Hawaii—A single yearly dose of soldering acid (Reclast®, Novartis Pharmaceuticals Corp) in patients who have had suffered a hip fracture can significantly reduce the risk for a new fracture and overall mortality, researchers reported at the American Society of Bone and Mineral Research (ASBMR) annual meeting, in Honolulu.¹ Kenneth W. Lyles, MD, reporting for the HORIZON recurrent fracture trial researchers, provided an early look at data that were released online by the New England Journal of Medicine and will appear in the journal's November 1 print edition.² Dr. Lyles is associate professor of geriatrics at Duke University Medical Center, in Durham, North Carolina.

The randomized, double-blind, placebo-controlled trial of 1065 patients randomized to yearly 5-mg intravenous zoledronic acid and 1062 patients randomized to placebo found that zoledronic acid

•     reduced new clinical fracture risk by 35%
  
•     reduced any-cause mortality by 28%
  
•     was not associated with increased risk for jaw osteonecrosis,
      abnormal heart rhythms, or other serious adverse events

In an accompanying editorial, Karim Anton Calis, PharmD, MPH, and Frank Pucino, PharmD, describe the results of this study as "both powerful and compelling. The reduction in fracture incidence and death was striking and clearly establishes the need for pharmacologic intervention in patients who fracture a hip."³

In an interview before the ASBMR presentation, CIAOMed asked Dr. Lyles whether Reclast should become standard-of-care for patients over age 50 who have hip fractures. We also wondered whether clinicians should be paying more attention to vitamin D levels in hip fracture patients, whose levels in this study were unexpectedly low at baseline.

"I have a bias, but I feel that patients over 50 who have had hip fractures should be getting Reclast as standard-of care," Dr. Lyles said. "Also, without question, doctors should be paying more attention to vitamin D levels in hip fracture patients."

Treatment reduced new clinical fractures, death from all causes

The patients in this study were mean age 74.5 years and were administered zoledronic acid or placebo 90 days after surgical repair of a hip fracture. Median follow-up was 1.9 years, and new clinical fracture was the primary study endpoint.

Because vitamin D levels were a concern, the protocol was originally designed to include a loading dose of vitamin to any patient with a vitamin D deficiency 2 weeks before administration of the study drug. "Since very high rates of vitamin D deficiency were observed in the first 385 patients who underwent randomization, a subsequent protocol amendment provided for a loading dose of vitamin D in all patients, regardless of the level of serum 25-hydroxyvitamin D. This approach might explain the low rate of hypocalcemia (three patients) in our study," Dr. Lyles reported.

Compared with placebo, treatment with zoledronic acid reduced the rate of new fractures from 13.9% to 8.6%, a 35% risk reduction (P = .001); reduced new vertebral fracture rates from 3.8% to 1.7% (P = .02); and reduced the rates for new nonvertebral fractures from 10.7% to 7.6% (P = .03). Treatment also reduced mortality from 13.3% to 9.6%, a 28% reduction in deaths from any cause (P = .01).

Adverse event rates were similar overall between the two groups, but more patients in the zoledronic acid group reported pyrexia, myalgia, bone or musculoskeletal pain. More patients in the placebo group reported having fallen.

Dr. Lyles added, "We cannot say what the positive effect [of zoledronic acid] on mortality was at this time, since only part of the reduction in death can be attributed to the reduction in new fractures after hip fracture. We will need to analyze our data further."

References