Original Article

Osteoporosis International

, Volume 23, Issue 3, pp 1131-1140

Dose–response study of denosumab on bone mineral density and bone turnover markers in Japanese postmenopausal women with osteoporosis

  • T. NakamuraAffiliated withDepartment of Orthopedics, University of Occupational and Environmental Health Email author 
  • , T. MatsumotoAffiliated withDepartment of Medicine and Bioregulatory Science, University of Tokushima Graduate School of Health Biosciences
  • , T. SugimotoAffiliated withDepartment of Internal Medicine 1, Shimane University Faculty of Medicine
  • , M. ShirakiAffiliated withResearch Institute and Practice for Involutional Diseases

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Abstract

Summary

The efficacy and safety of denosumab were evaluated in Japanese postmenopausal women with osteoporosis. Total hip and distal 1/3 radius bone mineral densities (BMDs) were increased, and lumbar spine BMD was increased in magnitude with increasing dose. Bone turnover markers significantly decreased compared with placebo. Denosumab was well tolerated in Japanese subjects.

Introduction

The efficacy and safety of three doses of denosumab were compared with a placebo over 12 months in Japanese postmenopausal women with osteoporosis.

Methods

In this phase 2 multicenter, randomized, placebo-controlled study, 226 subjects were randomized and 212 subjects received at least 1 dose of investigational product, subcutaneously. All subjects also received daily supplements of at least 600 mg elemental calcium and 400 IU vitamin D from the beginning of screening through 12 months of treatment.

Results

Compared with placebo, denosumab (14, 60, and 100 mg) showed significant increases in percent BMD values of lumbar spine (5.25, 6.27, and 7.00) and total hip (3.90, 3.69, and 4.35) from baseline in 12 months. Distal 1/3 radius BMD was also significantly increased except at the 100-mg dose (1.82, 1.35, and 1.15). Denosumab significantly decreased the serum C-terminal crosslinking telopeptide of type 1 collagen and urinary N-terminal crosslinking telopeptide of type I collagen/urinary creatinine levels in 8 days, and bone alkaline phosphatase in 3 months. No new vertebral fracture was observed on spinal radiographs in either group. The overall incidences of adverse events were similar in the denosumab groups and the placebo group. No subject developed antibodies to denosumab. These results were similar to those obtained in the US phase 2 study.

Conclusions

Denosumab 60 mg could be an effective dose for Japanese postmenopausal women with osteoporosis as was shown in the Caucasian population.

Keywords

AMG 162 BMD Bone ALP Serum CTX-I Urinary NTX-I/Cr