Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass

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Bone, Henry G.¹; Bolognese, Michael A.²; Yuen, Chui Kin³; Kendler, David L.⁴; Miller, Paul D.⁵; Yang, Yu-Ching⁶; Grazette, Luanda⁶; San Martin, Javier⁶; Gallagher, J. Christopher⁷

Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass

J Clin Endocrinol Metab. April 2011;96(4):972-980

©2011 The Endocrine Society

Affiliations

¹Michigan Bone and Mineral Clinic, Detroit, Michigan 48236

²Bethesda Health Research Center, Bethesda, Maryland 20817

³University of Manitoba, Winnipeg, Manitoba, Canada R3T 2N2

⁴Clinical Research Centre, Vancouver, British Columbia, Canada V6H 3X8

⁵Colorado Center for Bone Research, Lakewood, Colorado 80227

⁶Amgen Inc., Thousand Oaks, California 91320;

⁷Creighton University Medical Center, Omaha, Nebraska 68131
Abstract

Context: Denosumab treatment for 24 months increased bone mineral density (BMD) and reduced bone turnover markers (BTM) in postmenopausal women.

Objective: The aim was to determine the effects of prior denosumab or placebo injections on BMD, BTM, and safety over 24 months after treatment discontinuation.

Design: We conducted an off-treatment extension of a phase 3, randomized, double-blind, parallel-group study.

Participants: A total of 256 postmenopausal women with a mean age of 59 yr and a mean lumbar spine T-score of −1.61 at randomization participated in the study.

Interventions: Participants received placebo or 60 mg denosumab every 6 months for 24 months, followed by 24 months off treatment.

Main Outcome Measures: We measured the percentage changes in BMD and BTM, and evaluated safety.

Results: Of the 256 participants enrolled in the posttreatment phase, 87% completed the study. During 24 months of denosumab treatment, BMD increased (lumbar spine, 6.4%; total hip, 3.6%; 1/3 radius, 1.4%), and BTM decreased (serum C-terminal telopeptide of type 1 collagen, 63%; and N-terminal propeptide of type 1 procollagen, 47%), compared with placebo. After discontinuation, BMD declined, but the previously treated denosumab group maintained higher BMD than the previously treated placebo group at these sites (P ≤ 0.05). Final BMD at month 48 strongly correlated with month 0 BMD. After denosumab discontinuation, BTM increased above baseline within 3 months (serum C-terminal telopeptide of type 1 collagen) or 6 months (N-terminal propeptide of type 1 procollagen) and returned to baseline by month 48. Adverse event rates during the off-treatment phase were similar between groups.

Conclusions: In postmenopausal women with low BMD, the effects of 60 mg denosumab treatment for 24 months on BMD and BTM are reversible upon discontinuation, reflecting its biological mechanism of action. Residual BMD measurements remained above those of the group previously treated with placebo.
Links

DOI: 10.1210/jc.2010-1502

PubMed: 21289258

WoS: 000289242800038
History

Received: 2010-07-01

Accepted: 2010-12-23

Online: 2011-02-02

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