Denosumab in postmenopausal women with low bone mineral density - PubMed (original) (raw)
Clinical Trial
. 2006 Feb 23;354(8):821-31.
doi: 10.1056/NEJMoa044459.
E Michael Lewiecki, Stanley B Cohen, Michael A Bolognese, Grattan C Woodson, Alfred H Moffett, Munro Peacock, Paul D Miller, Samuel N Lederman, Charles H Chesnut, Douglas Lain, Alan J Kivitz, Donna L Holloway, Charlie Zhang, Mark C Peterson, Pirow J Bekker; AMG 162 Bone Loss Study Group
Affiliations
- PMID: 16495394
- DOI: 10.1056/NEJMoa044459
Free article
Clinical Trial
Denosumab in postmenopausal women with low bone mineral density
Michael R McClung et al. N Engl J Med. 2006.
Free article
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.
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.
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.
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.).
Copyright 2006 Massachusetts Medical Society.
Comment in
- The long and the short of bone therapy.
Whyte MP. Whyte MP. N Engl J Med. 2006 Feb 23;354(8):860-3. doi: 10.1056/NEJMe068003. N Engl J Med. 2006. PMID: 16495400 No abstract available. - Anti-RANKL therapy--implications for the bone-vascular-axis in CKD? Denosumab in post-menopausal women with low bone mineral density.
Westenfeld R, Ketteler M, Brandenburg VM. Westenfeld R, et al. Nephrol Dial Transplant. 2006 Aug;21(8):2075-7. doi: 10.1093/ndt/gfl245. Epub 2006 May 15. Nephrol Dial Transplant. 2006. PMID: 16702197 No abstract available. - Denosumab in postmenopausal women with low bone mineral density.
Schwartzman J, Yazici Y. Schwartzman J, et al. N Engl J Med. 2006 Jun 1;354(22):2390-1; author reply 2390-1. doi: 10.1056/NEJMc060819. N Engl J Med. 2006. PMID: 16738280 No abstract available. - Denosumab in postmenopausal women with low bone mineral density.
Rifkin WD. Rifkin WD. N Engl J Med. 2006 Jun 1;354(22):2390-1; author reply 2390-1. N Engl J Med. 2006. PMID: 16742010 No abstract available. - Does denosumab improve low BMD in postmenopausal women?
Favus MJ. Favus MJ. Nat Clin Pract Endocrinol Metab. 2006 Nov;2(11):600-1. doi: 10.1038/ncpendmet0328. Nat Clin Pract Endocrinol Metab. 2006. PMID: 17082802 No abstract available. - Denosumab in postmenopausal women with low bone mineral density.
Loprinzi CL. Loprinzi CL. Curr Oncol Rep. 2006 Jul;8(4):267-8. doi: 10.1007/s11912-006-0031-7. Curr Oncol Rep. 2006. PMID: 17269187 No abstract available. - Denosumab in postmenopausal women with low bone mineral density.
Teng GG, Patkar NM, Saag KG. Teng GG, et al. Curr Rheumatol Rep. 2007 Apr;9(1):48; discussion 48-9. Curr Rheumatol Rep. 2007. PMID: 17437667 No abstract available.
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