Literature DB >> 21927920

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

T Nakamura1, T Matsumoto, T Sugimoto, M Shiraki.   

Abstract

UNLABELLED: 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.

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Year:  2011        PMID: 21927920     DOI: 10.1007/s00198-011-1786-8

Source DB:  PubMed          Journal:  Osteoporos Int        ISSN: 0937-941X            Impact factor:   4.507


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5.  Impaired residual renal function predicts denosumab-induced serum calcium decrement as well as increment of bone mineral density in non-severe renal insufficiency.

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