Annual Infusion of Zoledronic Acid (Reclast) Cuts Risk After Hip Repair

September 18, 2007

HONOLULU -- An annual infusion of zoledronic acid (Reclast) following surgical repair of a fractured hip reduced the risk of a new fracture by 35% and mortality by 28% compared with placebo, researchers here said.

HONOLULU, Sept. 18 -- An annual infusion of zoledronic acid (Reclast) following surgical repair of a fractured hip reduced the risk of a new fracture by 35% and mortality by 28% compared with placebo, researchers here said.

The rate of any fracture was 8.6% in those given zoledronic acid and 13.9% in the placebo group (P=0.001) and mortality rates were 9.6% versus 13.3% respectively (P=0.01), Kenneth W. Lyles, M.D., of Duke University Medical Center, reported at the American Society for Bone and Mineral Research meeting and online in the New England Journal of Medicine.

The rate of new clinical vertebral fracture was reduced from 3.8% to 1.7% (P=0.02), while the nonvertebral fracture rate was reduced from 10.7% to 7.6% (P=0.03), he said.

The HORIZON (Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly) recurrent fracture trial randomized 1,065 hip fracture patients to once yearly intravenous zoledronic acid (5 mg) within 90 days of surgical repair and 1,062 patients to placebo. The mean age of patients was 74 and all patients received supplemental vitamin D and calcium. Patients were followed for a median of 1.9 years.

Dr. Lyles said the a placebo-controlled study for patients with a high risk for fracture raised some ethical concerns, since current guidelines recommend bisphosphonate treatment for secondary prevention of fractures in these patients. But, he said, patients recruited for the trial "could not tolerate, or would not take oral bisphosphonate."

Moreover, he said, the trial did permit "open-label concomitant use of several approved osteoporosis therapies." Despite that option, and for reasons that were not explained by Dr. Lyles and colleagues, less than 12% of patients in either group received concurrent treatment with approved osteoporosis therapies.

In an editorial that accompanied the study, Karim Anton Calis, Pharm.D., M.P.H., and Frank Pucino, Pharm.D., of the National Institutes of Health, called the HORIZON results "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."

The editorialists wrote, however, that other osteoporosis treatments should also be examined in hip fracture patients because there is "no reason to believe that the positive effects on morbidity and mortality are unique to zoledronic acid or bisphosphonates in general."

Among other findings of the study:

  • There were 92 new clinical fractures in patients given zoledronic acid on versus 132 in the placebo patients.
  • There were 101 deaths in the zoledronic acid arm versus 141 in the placebo arm.
  • Time to clinical fracture was 39.4 months in the zoledronic acid arm versus 36.4 months in the placebo arm.
  • The adverse event rate was higher in the zoledronic acid group than in the placebo group (82.3% versus 80.6%, P=0.34), but only myalgia and pyrexia (any event or after first infusion) occurred significantly more often in the zoledronic acid group (P