The antiresorptive effects of a single dose of zoledronate persist for two years: a randomized, placebo-controlled trial in osteopenic postmenopausal women.
BACKGROUND
Annual iv administration of 5 mg zoledronate decreases fracture risk. The optimal dosing interval of 5 mg zoledronate is not known.


OBJECTIVE
Our objective was to determine the duration of antiresorptive action of a single 5-mg dose of iv zoledronate.


METHODS
We conducted a double-blind, randomized, placebo-controlled trial over 2 yr at an academic research center, in a volunteer sample of 50 postmenopausal women with osteopenia.


METHODS
Intervention included 5 mg zoledronate.


METHODS
Biochemical markers of bone turnover and bone mineral density of the lumbar spine, proximal femur, and total body.


RESULTS
Compared with placebo, zoledronate treatment decreased mean levels of each of four markers of bone turnover by at least 38% (range 38-45%) for the duration of the study (P < 0.0001 for each marker). After 2 yr, bone mineral density was higher in the zoledronate group than the placebo group by an average of 5.7% (95% confidence interval = 4.0-7.4) at the lumbar spine, 3.9% (2.2-5.7) at the proximal femur, and 1.7% (0.8-2.5) at the total body (P < 0.0001 for each skeletal site). Between-groups differences in markers of bone turnover and bone mineral density were similar at 12 and 24 months. Mild secondary hyperparathyroidism was present throughout the study in the zoledronate group.


CONCLUSIONS
The antiresorptive effects of a single 5-mg dose of zoledronate are sustained for at least 2 yr. The magnitudes of the effects on markers of bone turnover and bone mineral density are comparable at 12 and 24 months. Administration of zoledronate at intervals of up to 2 yr may be associated with antifracture efficacy; clinical trials to investigate this possibility are justified.
Grey
Andrew
A
Department of Medicine, University of Auckland, Private Bag 92 019, Auckland, New Zealand. a.gray@auckland.ac.nz
Bolland
Mark J
MJ
Wattie
Diana
D
Horne
Anne
A
Gamble
Greg
G
Reid
Ian R
IR
D000368:Aged; D001682:Biological Availability; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004164:Diphosphonates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004355:Drug Stability; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000378:metabolism; D010919:Placebos; D013997:Time Factors; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D003692:Delayed-Action Preparations; D004164:Diphosphonates; D007093:Imidazoles; D010919:Placebos; D000077211:Zoledronic Acid