Yonsei Med J.  2016 Jul;57(4):905-914. 10.3349/ymj.2016.57.4.905.

Assessment of Denosumab in Korean Postmenopausal Women with Osteoporosis: Randomized, Double-Blind, Placebo-Controlled Trial with Open-Label Extension

• Koh JM
• Chung DJ
• Chung YS
• Kang MI
• Kim IJ
• Min YK
• Oh HJ
• Park IH
• Lee YS
• Kravitz B
• Waterhouse B
• Nino A
• Fitzpatrick LA

• KMID: 2374122
• DOI: http://doi.org/10.3349/ymj.2016.57.4.905

Abstract

PURPOSE
The efficacy and safety of denosumab was compared with placebo in Korean postmenopausal women with osteoporosis in this phase III study.
MATERIALS AND METHODS
Women aged 60 to 90 years with a T-score of <-2.5 and ≥-4.0 at the lumbar spine or total hip were randomized to a single 60 mg subcutaneous dose of denosumab or placebo for the 6-month double-blind phase. Eligible subjects entered the 6-month open-label extension phase and received a single dose of denosumab 60 mg.
RESULTS
Baseline demographics were similar in the 62 denosumab- and 64 placebo-treated subjects who completed the double-blind phase. Treatment favored denosumab over placebo for the primary endpoint {mean percent change from baseline in lumbar spine bone mineral density (BMD) at Month 6 [3.2% (95% confidence interval 2.1%, 4.4%; p<0.0001)]}; and secondary endpoints (mean percent change from baseline in lumbar spine BMD at Month 1, total hip, femoral neck, and trochanter BMD at Months 1 and 6, and median percent change from baseline in bone turnover markers at Months 1, 3, and 6). Endpoint improvements were sustained over 12 months in the open-label extension (n=119). There were no new or unexpected safety signals.
CONCLUSION
Denosumab was well tolerated and effective in increasing BMD and decreasing bone turnover markers over a 12-month period in Korean postmenopausal women. The findings of this study demonstrate that denosumab has beneficial effects on the measures of osteoporosis in Korean postmenopausal women.

Keyword

Denosumab; postmenopausal osteoporosis; Korea; bone mineral density; biochemical markers of bone turnover

MeSH Terms

Aged
Aged, 80 and over
*Asian Continental Ancestry Group
Bone Density
Bone Density Conservation Agents/*therapeutic use
Denosumab/*therapeutic use
Double-Blind Method
Female
Femur
Femur Neck
Humans
Lumbar Vertebrae
Middle Aged
Osteoporosis, Postmenopausal/*drug therapy/*ethnology
Postmenopause
Republic of Korea
Bone Density Conservation Agents
Denosumab

Figure

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  Fig. 1 Study design. SC, subcutaneous.

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  Fig. 2 Subject disposition. *Some subjects had more than 1 reason for failing screening.

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  Fig. 3 Primary endpoint - Mean percent change from baseline in BMD in lumbar spine. BMD measurements consisted of last observation carried forward (LOCF) values. Error bars are 95% confidence intervals for the mean percent change from baseline BMD at the lumbar spine (unadjusted). Baseline for the placebo → denosumab group is the end of double-blind phase. BMD, bone mineral density.

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  Fig. 4 Secondary endpoints - mean/median percent change from baseline in BMD in total hip, femoral neck, and trochanter and in bone turnover markers, s-CTX and s-PINP. BMD measurements consisted of last observation carried forward (LOCF) values, and bone turnover marker measurements consisted of observed values. Error bars for BMD endpoints are 95% confidence intervals for the mean percent change from baseline BMD. Error bars for bone turnover markers are (Q1, Q3). Baseline for the placebo → denosumab group is the end of double-blind phase. BMD, bone mineral density; s-CTX, serum C-terminal telopeptide of type I collagen; s-PINP, serum procollagen type I N-terminal propeptide.

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