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Denosumab in postmenopausal women with low bone mineral density.
- Source :
-
The New England journal of medicine [N Engl J Med] 2006 Feb 23; Vol. 354 (8), pp. 821-31. - Publication Year :
- 2006
-
Abstract
- Background: Receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162) binds RANKL with high affinity and specificity and inhibits RANKL action.<br />Methods: The efficacy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 412 postmenopausal women with low bone mineral density (T score of -1.8 to -4.0 at the lumbar spine or -1.8 to -3.5 at the proximal femur). Subjects were randomly assigned to receive denosumab either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 210 mg), open-label oral alendronate once weekly (at a dose of 70 mg), or placebo. The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase.<br />Results: Denosumab treatment for 12 months resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent (as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo), at the total hip of 1.9 to 3.6 percent (as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo), and at the distal third of the radius of 0.4 to 1.3 percent (as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo). Near-maximal reductions in mean levels of serum C-telopeptide from baseline were evident three days after the administration of denosumab. The duration of the suppression of bone turnover appeared to be dose-dependent.<br />Conclusions: In postmenopausal women with low bone mass, denosumab increased bone mineral density and decreased bone resorption. These preliminary data suggest that denosumab might be an effective treatment for osteoporosis. (ClinicalTrials.gov number, NCT00043186.).<br /> (Copyright 2006 Massachusetts Medical Society.)
- Subjects :
- Alendronate adverse effects
Alendronate pharmacology
Alendronate therapeutic use
Antibodies, Monoclonal adverse effects
Antibodies, Monoclonal pharmacology
Antibodies, Monoclonal, Humanized
Biomarkers blood
Bone Density Conservation Agents pharmacology
Bone Remodeling drug effects
Bone Resorption blood
Bone Resorption drug therapy
Denosumab
Double-Blind Method
Female
Humans
Injections, Subcutaneous
Middle Aged
Osteoporosis, Postmenopausal physiopathology
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B
Antibodies, Monoclonal therapeutic use
Bone Density drug effects
Bone Density Conservation Agents therapeutic use
Carrier Proteins antagonists & inhibitors
Membrane Glycoproteins antagonists & inhibitors
Osteoporosis, Postmenopausal drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1533-4406
- Volume :
- 354
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The New England journal of medicine
- Publication Type :
- Academic Journal
- Accession number :
- 16495394
- Full Text :
- https://doi.org/10.1056/NEJMoa044459