Results of a US clinical trial suggest that an annual infusion of Reclast (zoledronic acid), an osteoporosis drug, improved survival and reduced the risk of further clinical fractures in elderly patients who had undergone broken hip repair.
The study is published in the New England Journal of Medicine and was sponsored by the maker of the drug, Novartis.
Although other studies on osteoporosis drugs have already suggested they may benefit the prevention of fractures, this is the first study to concentrate on older patients who have undergone a hip repair and who have more coexisting conditions and a higher risk of falls.
Conducted by lead author Dr Kenneth Lyles of Duke University Medical Center, Durham, North Carolina, and colleagues, the study was called the The Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Recurrent Fracture Trial.
The trial was a multi-center, randomized, double-blind, placebo-controlled trial involving over 2,000 patients with recent hip fracture.
1,065 patients were randomly assigned to receive yearly infusions of Reclast (5 mg dose) and 1,062 patients received a placebo. The infusions lasted 15 minutes.
The participants were given the dose within 90 days of having an operation to repair a hip fracture.
All participants were also given Vitamin D and calcium. The mean age was 74.5 and the median follow up period was 1.9 years.
The results showed that:
- A total of 424 new fractures occurred in 231 patients during the follow up.
- Rates of new clinical fracture were 8.6 per cent in the Reclast group and 13.9 per cent in the placebo group.
- Reclast significantly reduced the risk of new clinical fracture by 35 per cent compared to placebo.
- Rates of new vertebral fractures were 1.7 per cent for Reclast and 3.8 per cent for placebo.
- Rates of new non vertebral fractures were 7.6 per cent for Reclast and 10.7 per cent for placebo.
- 101 out of 1,054 (9.6 per cent) patients in the Reclast group died during the study, as did 141 out of 1,057 (13.3 per cent) in the placebo group.
- This was a reduction in death rate in the Reclast group by 28 per cent, from any cause.
- In the Reclast group the most frequently observed adverse events were pyrexia (fever), myalgia (muscle pain), and bone and musculoskeletal pain.
- There were no reported cases of osteonecrosis (loss of blood supply to the bone).
- No adverse effects on the healing of fractures were observed.
- Renal and cardiovascular events, such as atrial fibrillation and stroke occurred to the same extent in both groups.
The researchers concluded that:
“An annual infusion of zoledronic acid within 90 days after repair of a low-trauma hip fracture was associated with a reduction in the rate of new clinical fractures and improved survival.”
Lyles and colleagues wrote that the effectiveness of current treatments for fracture reduction, which rely on patients taking bisphosphonate tablets on a daily basis, is reduced because patients, and frail elderly ones in particular, either stop taking the tablets or take them irregularly. They hope that the once a year alternative tested in this trial now offers a better option for this patient group.
The US Food and Drug Administration (FDA) approved Reclast for the treatment of post menopausal osteoporosis last month, August 2007.
In 2002, under the brand name Zometa, the FDA approved the drug for the treatment of cancer patients.
In the US, there are more than 300,000 hip fractures a year, mostly in frail elderly people.
Often the case with hip fractures in the elderly is a gradual decline in quality of life, and 20 per cent die within a year of the fracture.
“Zoledronic Acid and Clinical Fractures and Mortality after Hip Fracture.”
Lyles, Kenneth W., Colon-Emeric, Cathleen S., Magaziner, Jay S., Adachi, Jonathan D., Pieper, Carl F., Mautalen, Carlos, Hyldstrup, Lars, Recknor, Chris, Nordsletten, Lars, Moore, Kathy A., Lavecchia, Catherine, Zhang, Jie, Mesenbrink, Peter, Hodgson, Patricia K., Abrams, Ken, Orloff, John J., Horowitz, Zebulun, Eriksen, Erik Fink, Boonen, Steven, the HORIZON Recurrent Fracture Trial.
N Engl J Med 2007 0: NEJMoa074941.
Published online 17th September 2007.
Written by: Catharine Paddock