medwireNews: Women with healthy bone mineral density (BMD) may benefit from occasional infusions of zoledronate between age 50 and 60 years, say researchers who report a significant decrease in the risk for vertebral fracture with this strategy.
“Early postmenopausal women who wish to reduce their risk of fracture could consider a strategy involving the administration of zoledronate either every 5 years or every 10 years,” write Mark Bolland (University of Auckland, New Zealand) and co-authors in The New England Journal of Medicine.
“The cost of the treatment, either to individual patients or to health systems, is likely to be low because the drug is generic and the frequency of administration low,” they emphasize.
For the study, 1054 postmenopausal women, aged an average of 56 years, were randomly assigned to receive a 5 mg infusion of zoledronate at baseline followed by a second dose 5 years later, or an initial dose of zoledronate followed by placebo after 5 years, or placebo at both timepoints.
At baseline all the women had a BMD T score between 0 and –2.5 at the lumbar spine, femoral neck, or hip, where a score of –1 or above is considered to be normal BMD, the researchers explain.
Overall, 95.2% of participants completed 10 years of follow-up. During this time a new morphometric vertebral fracture, with at least a 20% change in vertebral height from baseline, was diagnosed in 6.3% of women given two doses of zoledronate, 6.6% of women given one dose of zoledronate, and 11.1% of women given double placebo.
This gave a significant relative risk (RR) for vertebral fracture of 0.56 for two doses of zoledronate versus double placebo in the modified intention-to-treat population after adjusting for missing data, and a significant RR of 0.59 for one dose of zoledronate versus double placebo, with a pooled RR of 0.58 for any zoledronate versus placebo.
The number needed to treat to prevent a new morphometric vertebral fracture over 10 years was 21 in the double zoledronate arm and 22 in the single zoledronate arm, report Bolland et al.
Both two doses and one dose of zoledronate also significantly reduced the risk for any type of fracture versus double placebo (RR=0.70 and 0.77, respectively), and there was a similar pattern for the risk for fragility and major osteoporotic fractures, the researchers add.
The team also investigated the impact of zoledronate on BMD of the total hip and spine over the study. At the 10-year checkpoint, there was a 7.4–8.8 percentage point difference at these two sites between the patients given two doses of zoledronate versus two doses of placebo, and a 5.0–6.3 percentage points difference between those given one dose of zoledronate versus two of placebo. The difference between the double and single zoledronate groups was 2.4–2.5 percentage points.
In addition, the team assessed levels of the bone turnover markers procollagen type 1 N-terminal propeptide and the beta isomer of C-terminal telopeptide of type 1 collagen. While bone turnover markers decreased at the 5-year checkpoint by 30–40% in the women give zoledronate at baseline, women given placebo had stable or increasing levels of these biomarkers. And at 10 years, the women given a second dose of zoledronate continued to have stable levels whereas the women given placebo as their second infusion had a slow increase in the bone turnover biomarkers.
The investigators note that there were “few adverse events” in the study. The first dose of zoledronate was associated with uveitis in 1.1% of recipients and episcleritis in 0.1% but there were no incidences after the second dose or in the double placebo arm. There were no reports of jaw osteonecrosis or atypical femoral fractures.
Discussing the findings in an accompanying editorial, Roland Chapurlat (Hôpital E Herriot, Lyon, France) writes that “[t]hese results are important not only because vertebral fracture is a major fracture but also because the results provide clinical perspectives for the prevention of primary fractures.”
He explains the study adds evidence to dispute the belief that “osteoporosis medications are mainly efficacious in women with the lowest bone mineral density T scores” and emphasizes that targeting women with a low fracture risk could have “a major effect on the population despite a small benefit at the individual level” because around 10% of women aged less than 65 years will experience a fracture over 10 years.
Recognizing that patient adherence to long-term anti-osteoporosis therapy is “often challenging,” Chapurlat concludes that “a very infrequent drug regimen presents a real opportunity” for primary prevention.
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