Intravenous zoledronate reduces fracture risk (5mg at 18mo intervals) and prevents bone loss (doses of 1-5mg for 3 to >5y), but the duration of action of a single 5mg dose and the effects of lower doses beyond 5 years are unknown. We report the second open-label extension (years 5-10) of a 2y randomized, multidose, placebo-controlled, double-blinded trial. 116 older women who completed 5y of participation either continued observation without further treatment (zoledronate 5mg and placebo at baseline) or received repeat doses of 1mg or 2.5mg zoledronate (zoledronate 1mg and zoledronate 2.5mg at baseline, respectively). Outcomes were spine, hip and total body bone mineral density (BMD) and serum markers of bone turnover. After a single 5mg dose of zoledronate, mean BMD at the lumbar spine and total hip was maintained at or above baseline levels for 9 and 10 years, respectively. The mean level of the bone resorption marker β-C-terminal telopeptide of type I collagen (β-CTX) was at least 25% lower than that in the placebo group for 9 years. In women administered 5-yearly doses of 2.5mg zoledronate, mean BMD at the total hip and lumbar spine was maintained at or above baseline levels for 9 and 10 years, respectively. Redosing with 1mg or 2.5mg zoledronate at 5 years reduced bone turnover markers for 3-4 years. BMD increased for 3-4 years after redosing with 1mg zoledronate. In the group given 5-yearly 2.5mg zoledronate, β-CTX was at least 20% lower than that in the placebo group for 10 years.
Both a single baseline 5mg dose of zoledronate and 5-yearly doses of 1mg and 2.5mg zoledronate prevented bone loss at hip and spine for 8-10 years in older postmenopausal women. Clinical trials to evaluate the effects on fracture risk of these very infrequent and lower doses of zoledronate are justified.