Efficacy and safety of once-yearly zoledronic acid in Japanese patients with primary osteoporosis: two-year results from a randomized placebo-controlled double-blind study (ZOledroNate treatment in Efficacy to osteoporosis; ZONE study).

Abstract

In a 2-year randomized, placebo-controlled study of 665 Japanese patients with primary osteoporosis, once-yearly administration of zoledronic acid (5 mg) reduced the risk of new morphometric vertebral fractures.

INTRODUCTION:

The purpose of this study was to determine the efficacy and safety of once-yearly intravenous infusion of ZOL in Japanese patients with primary osteoporosis.

METHODS:

This was a two-year multicenter, randomized, placebo-controlled, double-blind, parallel-group comparative study (ZONE Study). Subjects were 665 Japanese patients between the ages of 65 and 89 years who had prevalent vertebral fracture. Subjects were randomly assigned to receive once-yearly intravenous infusion of 5 mg of ZOL or placebo at baseline and 12 months.

RESULTS:

The 2-year incidence of new morphometric vertebral fracture was 3.0 % (10/330 subjects) in the ZOL group and 8.9 % (29/327) in the placebo group (p = 0.0016). The 24-month cumulative incidence of new morphometric vertebral fracture was 3.3 % in the ZOL group versus 9.7 % in the placebo group (log-rank test: p = 0.0029; hazard ratio: 0.35; 95 % confidence interval: 0.17-0.72). The cumulative incidence of any clinical fracture, clinical vertebral fracture, and non-vertebral fracture was significantly reduced in the ZOL group by 54, 70, and 45 %, respectively, compared to the placebo group. At 24 months, ZOL administration increased bone mineral density in the lumbar spine, femoral neck, and total hip (t test: p < 0.0001). No new adverse events or osteonecrosis of the jaw were observed in this study.

CONCLUSIONS:

Once-yearly administration of ZOL 5 mg to Japanese patients with primary osteoporosis reduced the risk of new morphometric vertebral fractures and was found to be safe.

• Authors: T Nakamura, M Fukunaga, T Nakano, H Kishimoto, M Ito, H Hagino, T Sone, A Taguchi, S Tanaka, M Ohashi, Y Ota, M Shiraki
• Journal: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA (Osteoporos Int) Vol. 28 Issue 1 Pg. 389-398 (01 2017) ISSN: 1433-2965 [Electronic] England
• PMID: 27631091 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Bone Density Conservation Agents
• Diphosphonates
• Imidazoles
• Zoledronic Acid

Topics

• Aged
• Aged, 80 and over
• Bone Density (drug effects)
• Bone Density Conservation Agents (adverse effects, pharmacology, therapeutic use)
• Diphosphonates (adverse effects, pharmacology, therapeutic use)
• Double-Blind Method
• Drug Administration Schedule
• Female
• Humans
• Imidazoles (adverse effects, pharmacology, therapeutic use)
• Infusions, Intravenous
• Japan (epidemiology)
• Male
• Osteoporosis (drug therapy, epidemiology, physiopathology)
• Osteoporotic Fractures (epidemiology, physiopathology, prevention & control)
• Spinal Fractures (epidemiology, physiopathology, prevention & control)
• Treatment Outcome
• Zoledronic Acid