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)

• Published in: Osteoporosis international Vol. 28; no. 1; pp. 389 - 398
• Main Authors: Nakamura, T., Fukunaga, M., Nakano, T., Kishimoto, H., Ito, M., Hagino, H., Sone, T., Taguchi, A., Tanaka, S., Ohashi, M., Ota, Y., Shiraki, M.
• Format: Journal Article
• Language: English
• Published: London Springer London 01.01.2017; Springer Nature B.V
• Subjects: Aged; Aged, 80 and over; Bone Density - drug effects; Bone Density Conservation Agents - adverse effects; Bone Density Conservation Agents - pharmacology; Bone Density Conservation Agents - therapeutic use; Bone mineral density; Clinical trials; Diphosphonates - adverse effects; Diphosphonates - pharmacology; Diphosphonates - therapeutic use; Double-Blind Method; Double-blind studies; Drug Administration Schedule; Endocrinology; Female; Femur; Fractures; Hip; Humans; Imidazoles - adverse effects; Imidazoles - pharmacology; Imidazoles - therapeutic use; Infusions, Intravenous; Intravenous administration; Japan - epidemiology; Jaw; Male; Medicine; Medicine & Public Health; Original; Original Article; Orthopedics; Osteonecrosis; Osteoporosis; Osteoporosis - drug therapy; Osteoporosis - epidemiology; Osteoporosis - physiopathology; Osteoporotic Fractures - epidemiology; Osteoporotic Fractures - physiopathology; Osteoporotic Fractures - prevention & control; Patients; Rheumatology; Spinal Fractures - epidemiology; Spinal Fractures - physiopathology; Spinal Fractures - prevention & control; Spine (lumbar); Treatment Outcome; Vertebrae; Zoledronic Acid; Clinical trials; Osteoporosis; Antiresorptives; Biochemical markers of bone turnover; Fracture prevention
• ISSN: 0937-941X; 1433-2965; 1433-2965
• DOI: 10.1007/s00198-016-3736-y

Summary 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.