Prolonged antiresorptive activity of zoledronate: a randomized, controlled trial.
Annual intravenous administration of 5 mg of zoledronate decreases fracture risk over 3 years. The optimal dosing interval of 5 mg of zoledronate is not known. In order to determine the duration of the antiresorptive action of a single 5-mg dose of intravenous zoledronate, we conducted a 3-year double-blind, randomized, placebo-controlled trial in a volunteer sample of 50 postmenopausal women with osteopenia. The coprimary endpoints were the bone turnover markers β-C-terminal telopeptide of type I collagen (β-CTX) and serum procollagen type-I N-terminal propeptide (P1NP). Secondary endpoints were bone mineral density (BMD) at the lumbar spine, total hip, and total body. After 3 years, mean (95% confidence interval) levels of serum β-CTX and P1NP were 44% (27-60) and 40% (24%-56%) lower in the zoledronate group (p < .001 versus placebo for each marker). BMD was higher in the zoledronate group than in the placebo group by an average of 6.8% (4.6%-9.1%) at the lumbar spine, 4.0% (1.8%-6.3%) at the total hip, and 2.0% (0.9%-3.0%) at the total body (p < .001 for each skeletal site). Between-group differences in markers of bone turnover and BMD were stable from 12 to 36 months. These data demonstrate that the antiresorptive effects of a single 5-mg dose of zoledronate are sustained for 3 years; clinical trials to investigate the antifracture efficacy of dosing intervals longer than 1 year are justified.
Grey
Andrew
A
Department of Medicine, University of Auckland, Auckland, New Zealand. a.grey@auckland.ac.nz
Bolland
Mark
M
Wattie
Diana
D
Horne
Anne
A
Gamble
Greg
G
Reid
Ian R
IR
D000368:Aged; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001862:Bone Resorption / Q000188:drug therapy*; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008875:Middle Aged; D010919:Placebos; D017698:Postmenopause; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D010919:Placebos; D000077211:Zoledronic Acid