Intravenous zoledronate therapy given once every 18 months, with minimal use of calcium supplements, was associated with an increase in bone mass and significantly reduced the risk of vertebral and nonvertebral fractures in postmenopausal women, compared with a placebo, based on data from a 6-year trial of 2,000 ambulatory women aged 65 and older with osteopenia.
The findings were presented at the annual meeting of the American Society for Bone and Mineral Research and published simultaneously in the New England Journal of Medicine.
Bisphosphonates have been shown to prevent fractures in osteoporosis patients, but their effectiveness has not been well studied in patients with osteopenia alone, noted Ian R. Reid, MD, of the University of Auckland, New Zealand, and his colleagues. “Many patients at high risk for fracture do not have T scores of less than –2.5 but rather have osteopenia in combination with other risk factors such as age.”
The researchers randomized 2,000 women aged 65 years and older with osteopenia to receive four infusions of zoledronate or a saline placebo every 18 months. A dietary intake of 1 g of calcium per day was advised, but calcium supplements were not provided; 2% of the women took supplements. Those not taking vitamin D before the trial were given a single 2.5-mg dose of cholecalciferol and a monthly 1.25-mg dose during the trial. Trial participants were followed for 6 years.
Courtesy Dr. Ian Reid
Dr. Ian Reid
Demographic characteristics were similar between the groups, and their T scores ranged from –1.0 to –2.5 at the total hip or femoral neck. The primary endpoint was the time to a first fragility fracture, defined as nonvertebral fractures and vertebral fractures confirmed by radiography.
Overall, 122 women in the zoledronate group experienced 131 fractures, and 190 women in the placebo group experienced 227 fractures (hazard ratio 0.63, P less than .001). Differences in bone mineral density between the two groups were observed by 3 years.
The number needed to treat to prevent a single fragility fracture was 10; the number needed to treat to prevent a symptomatic fracture was 20.
The findings were consistent with data on reduced fracture risk in osteoporosis patients treated with zoledronate. The study differed from other similar trials in its use of 18-month dosing intervals and low use of calcium supplements (2%), they noted.
The data were limited by the older age of the study individuals, so the results should not be extrapolated to younger women or individuals with normal bone mineral density, the researchers said. The results suggest that annual zoledronate dosing may be unnecessary, but further research is needed to explore longer dose intervals.
Dr. Reid disclosed grants from Health Research Council of New Zealand, nonfinancial support from Novartis during the study, and financial relationships with Amgen, Merck, Novartis, and Eli Lilly unrelated to the study.
SOURCE: Reid I et al. N Engl J Med. 2018 Oct 1. doi: 10.1056/NEJMoa1808082.