Five years of anti-resorptive activity after a single dose of zoledronate--results from a randomized double-blind placebo-controlled trial

Intravenous zoledronate 5 mg, administered annually, prevents fractures in people with osteoporosis, but the optimal dosing schedule is not known. Previously, we reported that a single dose of 5 mg zoledronate stably decreased bone turnover and increased bone mineral density (BMD) for 3 years in a randomized controlled trial in 50 postmenopausal women with osteopenia. We have now completed a 2-year double-blind extension of this trial, during which no additional treatment was administered. The primary endpoint was change in the bone turnover markers procollagen type-I N-terminal propeptide (P1NP) and β-C-terminal telopeptide of type I collagen (β-CTX); the secondary endpoint was change in BMD at lumbar spine, total hip and total body. Mean levels of the each of the bone turnover markers were lower in the zoledronate group throughout the study (P<0.0001 for each marker). After 5 years, mean (95% CI) levels of β-CTX and P1NP were 277 ng/L (150, 404) and 28 μg/L (16, 40) lower in the zoledronate group, corresponding to reductions of 48% and 45%, respectively. BMD was higher in the zoledronate group during the study (P<0.0001 for each site). After 5 years, BMD in the zoledronate group was higher by 4.2% (1.1, 7.2) at the lumbar spine, by 5.3% (2.7, 7.9) at the total hip, and by 2.7% (1.1, 4.2) at the total body. These findings suggest that the anti-resorptive effects of a single 5 mg dose of zoledronate persist for at least 5 years in postmenopausal women. Trials assessing the anti-fracture efficacy of dosing intervals of zoledronate of up to 5 years are justified.