Back to Search
Start Over
Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2011 Apr; Vol. 96 (4), pp. 972-80. Date of Electronic Publication: 2011 Feb 02. - Publication Year :
- 2011
-
Abstract
- Context: Denosumab treatment for 24 months increased bone mineral density (BMD) and reduced bone turnover markers (BTM) in postmenopausal women.<br />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.<br />Design: We conducted an off-treatment extension of a phase 3, randomized, double-blind, parallel-group study.<br />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.<br />Interventions: Participants received placebo or 60 mg denosumab every 6 months for 24 months, followed by 24 months off treatment.<br />Main Outcome Measures: We measured the percentage changes in BMD and BTM, and evaluated safety.<br />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.<br />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.
- Subjects :
- Aged
Algorithms
Antibodies, Monoclonal administration & dosage
Antibodies, Monoclonal adverse effects
Antibodies, Monoclonal pharmacology
Antibodies, Monoclonal, Humanized
Biomarkers blood
Bone Density Conservation Agents administration & dosage
Bone Density Conservation Agents adverse effects
Bone Density Conservation Agents pharmacology
Bone Density Conservation Agents therapeutic use
Denosumab
Double-Blind Method
Female
Follow-Up Studies
Fractures, Bone epidemiology
Fractures, Bone prevention & control
Humans
Middle Aged
Osteoporosis, Postmenopausal blood
Placebos
RANK Ligand administration & dosage
RANK Ligand adverse effects
RANK Ligand pharmacology
Antibodies, Monoclonal therapeutic use
Biomarkers analysis
Bone Density drug effects
Bone Remodeling drug effects
Osteoporosis, Postmenopausal drug therapy
RANK Ligand therapeutic use
Withholding Treatment
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7197
- Volume :
- 96
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 21289258
- Full Text :
- https://doi.org/10.1210/jc.2010-1502