In a randomized multidose trial, single doses of zoledronate (1-5 mg) prolonged antiresorptive activity ≥3 years in postmenopausal women with osteopenia.1 Results of the study were published in the Canadian Medical Association Journal.
For this open-label extension study, which was conducted over 3 years, the researchers evaluated the effects on bone mineral density (BMD) and bone turnover of zoledronate in late postmenopausal women with osteopenia. The study participants (n=152) were assigned to receive a single baseline dose of zoledronate 1 mg (n=39), 2.5 mg (n=38), or 5 mg (n=41), or placebo (n=34). The primary outcome of the study was change in spine BMD scores. Secondary outcomes included changes in hip BMD and biochemical serum markers of bone turnover.
At the 2-year follow-up, the use of zoledronate was shown to lead to increases in BMD compared with placebo, with a 5% increase with the 1-mg dose (95% CI, 3%-7%) and a 5.7% increase with both the 2.5-mg dose (95% CI, 3.7%-7.7%) and the 5-mg dose (95% CI, 3.7%-7.6%). After 5 years, the respective increases for zoledronate 1 mg, 2.5 mg, and 5 mg were 2% (95% CI, 1.1%-5%), 2.2% (95% CI, 1%-5.4%), and 5.1% (95% CI, 2.2%-8.1%).
At the 2-year follow-up, increases in hip BMD with zoledronate compared with placebo were as follows: 2.6% with zoledronate 1 mg (95% CI, 1.3%-3.9%), 4.1% with zoledronate 2.5 mg (95% CI, 2.9%-5.4%), and 4.7% with zoledronate 5 mg (95% CI, 3.4%-5.9%). After 5 years, the respective increases for zoledronate 1 mg, 2.5 mg, and 5 mg were: 1.8% (95% CI, –0.1%-3.8%), 2.8% (95% CI, 0.8%-4.8%), and 5.4% (95% CI, 3.5%-7.3%). BMD remained above baseline levels for 2 to 3 years in the zoledronate 1-mg group, for 3 to 4 years in the zoledronate 2.5-mg group, and for ≥5 years in the zoledronate 5-mg group.
Future clinical trials designed to evaluate the effects of fracture risk or of less frequent or lower doses of zoledronate than those currently recommended are warranted.
According to the investigators, the antiresorptive effects of single zoledronate doses of 1 mg, 2.5 mg, and 5 mg persist for ≥3 years in postmenopausal women with osteopenia. “These data clearly show that the offset of antiresorptive action of zoledronate is gradual, occurring over several years,” they concluded.
Grey A, Bolland MJ, Horne A, Mihov B, Gamble G, Reid IR. Duration of antiresorptive activity of zoledronate in postmenopausal women with osteopenia: a randomized, controlled multidose trial. CMAJ. 2017;189:E1130-E1136.