Benefits of the bisphosphonates may extend beyond fracture prevention to include reductions in cardiovascular and cancer events and possibly mortality, according to a New Zealand trial.
A more in-depth analysis of a six year trial of zoledronate in older women with osteopenia has found benefits on cardiovascular disease and some cancers consistent with those seen in observational studies .
Led by Professor Ian Reid of Auckland University, the study randomised 2,000 women over 65 years with a T score between -1.0 and -2.5 to four infusions of zolendronate (5mg) or placebo at 18-month intervals. Previously reported results showed significant reductions in vertebral and non-vertebral fractures among women in the zolendronate group compared those in the control group.
Now a more detailed analysis of the secondary safety outcomes in the trial has shown a 40% lower rate of myocardial infarction in the zoledronate group compared to the control group (43 events in 39 women vs 25 events in 24 women).
There were also a 24% lower risk of the composite cardiovascular endpoint (sudden death, myocardial infarction, coronary artery revascularisation, or stroke) in the zoledronate group compared to placebo.
Lower rates of cancer were seen in the zoledronate-treated women (rate ratio 0.68 [95% CI, 0.52 to 0.89]) with a notable difference in breast cancer incidence (rate ratio 0.59 [95% CI, 0.35 to 0.98]).
The hazard ratio for death was 0.65 (95% CI, 0.40 to 1.06; p = 0.08), and 0.51 (95% CI, 0.30 to 0.87) in those without incident fragility fracture.
The pattern of adverse events suggested that the protective effects began within the first year of zoledronate treatment and were progressive during the remaining 6-year study period
Writing in the Journal of Bone and Mineral Research, Professor Reid cautioned that the study was not specifically powered to show differences in these safety endpoints and they did not correct for multiple comparisons.
“However, the size of the possible benefits is such that were these effects real, they could have as great an impact as that of fracture prevention,” he wrote.
Each 1000 person-years of treatment with zoledronate would prevent 16.5 fragility fractures, 4.7 vascular events and 6.9 cancers, and mortality appeared to be reduced by about one-third in the zoledronate group, he noted.
“In isolation these findings could be regarded as intriguing, but there are a number of other studies that contain similar suggestions of benefit from anti-resorptive drugs on these outcomes,” said Professor Reid.
“These apparent beneficial effects justify further appropriately powered trials of zoledronate with these nonskeletal conditions as primary endpoints.”
Professor Reid declared he has received fees or research funding from Amgen, Merck, Novartis, and Eli Lilly.