Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2013 Jan;24(1):227-35.
doi: 10.1007/s00198-012-2052-4. Epub 2012 Jul 10.

Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial

M R McClung  1 , E M Lewiecki, M L Geller, M A Bolognese, M Peacock, R L Weinstein, B Ding, E Rockabrand, R B Wagman, P D Miller
Affiliations
Clinical Trial

Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial

M R McClung et al. Osteoporos Int. 2013 Jan.

Abstract

In a phase 2 study, continued denosumab treatment for up to 8 years was associated with continued gains in bone mineral density and persistent reductions in bone turnover markers. Denosumab treatment was well tolerated throughout the 8-year study.

Introduction: The purpose of this study is to present the effects of 8 years of continued denosumab treatment on bone mineral density (BMD) and bone turnover markers (BTM) from a phase 2 study.

Methods: In the 4-year parent study, postmenopausal women with low BMD were randomized to receive placebo, alendronate, or denosumab. After 2 years, subjects were reallocated to continue, discontinue, or discontinue and reinitiate denosumab; discontinue alendronate; or maintain placebo for two more years. The parent study was then extended for 4 years where all subjects received denosumab.

Results: Of the 262 subjects who completed the parent study, 200 enrolled in the extension, and of these, 138 completed the extension. For the subjects who received 8 years of continued denosumab treatment, BMD at the lumbar spine (N = 88) and total hip (N = 87) increased by 16.5 and 6.8 %, respectively, compared with their parent study baseline, and by 5.7 and 1.8 %, respectively, compared with their extension study baseline. For the 12 subjects in the original placebo group, 4 years of denosumab resulted in BMD gains comparable with those observed during the 4 years of denosumab in the parent study. Reductions in BTM were sustained over the course of continued denosumab treatment. Reductions also were observed when the placebo group transitioned to denosumab. Adverse event profile was consistent with previous reports and an aging cohort.

Conclusion: Continued denosumab treatment for 8 years was associated with progressive gains in BMD, persistent reductions in BTM, and was well tolerated.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Study design of the 4-year parent dose-ranging study with the different treatment regimens at months 24 and 48, and the 4-year extension study with all subjects receiving open-label denosumab 60 mg every 6 months. n = number of subjects who enrolled in the parent and extension study and those that completed each study
Fig. 2
Fig. 2
Effect of 8 years of continued denosumab treatment on BMD at the a lumbar spine, b total hip, and c one-third radius. BMD values are shown as percent change from parent study baseline (LSM + 95 % CI based on ANCOVA models adjusting for geographical location and parent study baseline BMD values). Gray boxes indicate the original 4-year parent study. Numbers shown at each time point reflect the number of subjects enrolled in the extension study with observed data at the selected time points of interest
Fig. 3
Fig. 3
Effect of 8 years of continued denosumab treatment on levels of a serum CTX and b BSAP. Bone turnover markers are shown as actual values (medians with Q1 to Q3 interquartile ranges). Gray boxes indicate the original 4-year parent study. Numbers shown at each time point reflect the number of subjects enrolled in the extension study with observed data at the selected time points of interest. Asterisk A calibration discrepancy at the central laboratory may have led to BSAP results in some individual samples to be falsely elevated by up to 14 % at months 90 and 96
See this image and copyright information in PMC

References

    1. Burgess TL, Qian Y, Kaufman S, Ring BD, Van G, Capparelli C, Kelley M, Hsu H, Boyle WJ, Dunstan CR, Hu S, Lacey DL. The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts. J Cell Biol. 1999;145:527–538. doi: 10.1083/jcb.145.3.527. - DOI - PMC - PubMed
    1. Lacey DL, Tan HL, Lu J, Kaufman S, Van G, Qiu W, Rattan A, Scully S, Fletcher F, Juan T, Kelley M, Burgess TL, Boyle WJ, Polverino AJ. Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo. Am J Pathol. 2000;157:435–448. doi: 10.1016/S0002-9440(10)64556-7. - DOI - PMC - PubMed
    1. Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93:165–176. doi: 10.1016/S0092-8674(00)81569-X. - DOI - PubMed
    1. Udagawa N, Takahashi N, Yasuda H, Mizuno A, Itoh K, Ueno Y, Shinki T, Gillespie MT, Martin TJ, Higashio K, Suda T. Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development and function. Endocrinology. 2000;141:3478–3484. doi: 10.1210/en.141.9.3478. - DOI - PubMed
    1. Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A. 1998;95:3597–3602. doi: 10.1073/pnas.95.7.3597. - DOI - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources