title: Five years of anti-resorptive activity after a single dose of zoledronate--results from a randomized double-blind placebo-controlled trial.
abstract: 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.
authors.affiliation: Department of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand. a.grey@auckland.ac.nz
authors.forename: Andrew
authors.initials: A
authors.lastname: Grey
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Bolland
authors.forename: Anne
authors.initials: A
authors.lastname: Horne
authors.forename: Diana
authors.initials: D
authors.lastname: Wattie
authors.forename: Meaghan
authors.initials: M
authors.lastname: House
authors.forename: Greg
authors.initials: G
authors.lastname: Gamble
authors.forename: Ian R
authors.initials: IR
authors.lastname: Reid
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000378:metabolism*; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D001862:Bone Resorption / Q000188:drug therapy / Q000378:metabolism; D024042:Collagen Type I / Q000097:blood; D004164:Diphosphonates / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D013997:Time Factors; D000077211:Zoledronic Acid
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D000077211:Zoledronic Acid