WASHINGTON — A single yearly infusion of zoledronic acid appears to prevent further bone loss in postmenopausal women with osteopenia and in women who have already had a hip fracture, two randomized controlled trials have concluded.
This is the first time the drug has been shown to be an effective preventive agent in treating osteopenic patients, said Dr. Chris Recknor, who presented the data in a poster session at an international symposium sponsored by the National Osteoporosis Foundation.
Using the drug prophylactically “allows clinicians a little more lead time in treating these patients, many of whom are at increased risk of a low-stress fracture,” said Dr. Recknor, an internist specializing in the treatment of osteoporosis in Gainesville, Ga.
The 2-year Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) prevention study cohort comprised 531 postmenopausal women with low bone mineral density (T scores of −1 to −2.5). They were randomized to one of three treatment regimens: two placebo infusions, given 12 months apart; two infusions of zoledronic acid 5 mg, given 12 months apart; or one infusion of 5 mg zoledronic acid, followed 12 months later by a placebo infusion.
The subjects' mean age was 60 years. Most (93%) were white. The study's main outcomes were 24-month changes in bone mineral density (BMD) at the lumbar spine, trochanter, femoral neck, distal radius, and total hip. The secondary end points were changes in markers of bone turnover. At 24 months (1 year after the second infusion), both active groups showed similar BMD increases at all sites that were significantly different from BMD changes with placebo. (See box.)
Both zoledronic acid regimens showed significant reductions in bone turnover markers compared with placebo. Markers in the double-infusion group were significantly lower than those in the single-infusion group.
Adverse events were most commonly observed in the first 3 days after the first infusion, when they were significantly more common in both active groups (60% vs. 25%). The most frequently reported were pain, fever, chills, myalgia, nausea, and headache. Adverse events were significantly lower after the second infusion, occurring in 18% of the double-infusion group, 11% of the single-infusion group, and 12% of the placebo group.
The study raises a tantalizing possibility, Dr. Recknor said in an interview. “You may be able to give this drug a couple of times to perimenopausal women and prevent the entire problem of bone loss.”
A subanalysis of a second HORIZON study has shown that zoledronic acid also benefits patients who have had a hip fracture—particularly the very elderly and those with the poorest bone quality.
The HORIZON Recurrent Fracture Trial included 2,127 patients with a recent hip fracture who were randomized to an annual infusion of 5 mg zoledronic acid or placebo and followed for up to 5 years. HORIZON-RFT concluded that the drug reduced the rate of recurrent fracture by 35% (N. Engl. J. Med. 2007;357:1799–809).
The subanalysis examined response rates within specific patient groups, said Denise Orwig, Ph.D., during a poster session at the meeting. The analysis showed that patients at the highest risk for a recurrent fracture—those who were at least 85 years old or who had a T score of less than −2.5 at the total hip—benefited the most from the treatment.
Although Dr. Orwig said it's unclear why the oldest, least-dense bones benefited the most, the finding does carry a strongly positive clinical implication. “These patients who are at the highest risk are also the ones who are the least likely to be treated,” said Dr. Orwig of the department of epidemiology and preventive medicine at the University of Maryland Medical Center, Baltimore. “The thought may be that they have already had multiple fractures and there is probably not a lot more that can be done. But this study showed us that these individuals can benefit and that we can have a big short-term impact on their bone density and possibly even reduce the risk of more fractures.”
In a third study presented at the meeting, a single infusion of zoledronic acid was shown to suppress serum markers of bone turnover significantly better than 6 months of daily oral raloxifene in postmenopausal women with low bone mineral density. (See story on p. 29.)
Novartis Pharmaceuticals Corp. sponsored the studies. Dr. Orwig has received research funding from the company, and Dr. Recknor is on the speakers bureau.
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