Clinical Trials Express: fracture risk reduction with denosumab in Japanese postmenopausal women and men with osteoporosis: denosumab fracture intervention randomized placebo controlled trial (DIRECT).

Abstract

CONTEXT:

Denosumab 60 mg sc injection every 6 months for 36 months was well tolerated and effective in reducing the incidence of vertebral, nonvertebral, and hip fracture in predominantly Caucasian postmenopausal women with osteoporosis.

OBJECTIVE:

The objective of this phase 3 fracture study was to examine the antifracture efficacy and safety of denosumab 60 mg in Japanese women and men with osteoporosis compared with placebo.

DESIGN AND SETTING:

A randomized, double-blind, placebo-controlled trial with an open-label active comparator as a referential arm was conducted.

PATIENTS:

Subjects were 1262 Japanese patients with osteoporosis aged 50 years or older, who had one to four prevalent vertebral fractures.

INTERVENTION:

Subjects were randomly assigned to receive denosumab 60 mg sc every 6 months (n = 500), placebo for denosumab (n = 511), or oral alendronate 35 mg weekly (n = 251). All subjects received daily supplements of calcium and vitamin D.

MAIN OUTCOME MEASURE:

The primary endpoint was the 24-month incidence of new or worsening vertebral fracture for denosumab vs placebo.

RESULTS:

Denosumab significantly reduced the risk of new or worsening vertebral fracture by 65.7%, with incidences of 3.6% in denosumab and 10.3% in placebo at 24 months (hazard ratio 0.343; 95% confidence interval 0.194-0.606, P = .0001). No apparent difference in adverse events was found between denosumab and placebo during the first 24 months of the study.

CONCLUSION:

These results provide evidence of the efficacy and safety of denosumab 60 mg sc every 6 months in Japanese subjects with osteoporosis.

• Authors: Toshitaka Nakamura, Toshio Matsumoto, Toshitsugu Sugimoto, Takayuki Hosoi, Takami Miki, Itsuo Gorai, Hideki Yoshikawa, Yoshiya Tanaka, Sakae Tanaka, Teruki Sone, Tetsuo Nakano, Masako Ito, Shigeyuki Matsui, Toshiyuki Yoneda, Hideo Takami, Ko Watanabe, Taisuke Osakabe, Masataka Shiraki, Masao Fukunaga
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 99 Issue 7 Pg. 2599-607 (Jul 2014) ISSN: 1945-7197 [Electronic] United States
• PMID: 24646104 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Placebos
• Denosumab
• Alendronate

Topics

• Aged
• Aged, 80 and over
• Alendronate (therapeutic use)
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Denosumab
• Female
• Humans
• Japan (epidemiology)
• Male
• Middle Aged
• Osteoporosis (drug therapy, epidemiology)
• Osteoporosis, Postmenopausal (drug therapy, epidemiology)
• Osteoporotic Fractures (epidemiology, etiology, prevention & control)
• Placebos
• Risk Factors
• Treatment Outcome