This Article Full Text Full Text (PDF) All Versions of this Article: 93/6/2149    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Google Scholar Articles by Bone, H. G. Articles by San Martin, J. PubMed PubMed Citation Articles by Bone, H. G. Articles by San Martin, J. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Osteoporosis Related Collections Calcium and Bone Metabolism Female Endocrinology

Effects of Denosumab on Bone Mineral Density and Bone Turnover in Postmenopausal Women

Michigan Bone and Mineral Clinic (H.G.B.), Detroit, Michigan 48236; The Bethesda Health Research Center (M.A.B.), Bethesda, Maryland 20817-1106; University of Manitoba (C.K.Y.), Winnipeg, Manitoba, Canada R3T 2N2; University of British Columbia (D.L.K.), Vancouver, British Columbia, Canada V6T 1Z4; and Amgen Inc. (H.W., Y.L., J.S.M.), Thousand Oaks, California 91320-1799

Address all correspondence and requests for reprints to: Henry G Bone, M.D., Michigan Bone and Mineral Clinic, 22201 Moross Road, Suite 260, Detroit, Michigan 48236. E-mail: hgbone.md{at}att.net.

Context: Denosumab is an investigational fully human monoclonal antibody against receptor activator of nuclear factor-B ligand, a mediator of osteoclastogenesis and osteoclast survival.

Objective: This study evaluated the ability of denosumab to increase bone mineral density (BMD) and decrease bone turnover markers (BTMs) in early and later postmenopausal women with low BMD.

Design and Setting: This 2-yr randomized, double-blind, placebo-controlled study was conducted in North America.

Participants: Subjects included 332 postmenopausal women with lumbar spine BMD T-scores between –1.0 and –2.5.

Interventions: Subjects were randomly assigned to receive denosumab sc, 60 mg every 6 months, or placebo. Randomization was stratified by time since onset of menopause (5 yr or > 5 yr).

Main Outcome Measures: The primary end point was the percent change in lumbar spine BMD by dual-energy x-ray absorptiometry at 24 months. Additional end points were percent change in volumetric BMD of the distal radius by quantitative computed tomography; percent change in BMD by dual-energy x-ray absorptiometry for the total hip, one-third radius, and total body; hip structural analysis; percent change in BTMs; and safety.

Results: Denosumab significantly increased lumbar spine BMD, compared with placebo at 24 months (6.5 vs. –0.6%; P<0.0001) with similar results for both strata. Denosumab also produced significant increases in BMD at the total hip, one-third radius, and total body (P < 0.0001 vs. placebo); increased distal radius volumetric BMD (P < 0.01); improved hip structural analysis parameters; and significantly suppressed serum C-telopeptide, tartrate-resistant acid phosphatase-5b, and intact N-terminal propeptide of type 1 procollagen. The overall incidence of adverse events was similar between both study groups.

Conclusions: Twice-yearly denosumab increased BMD and decreased BTMs in early and later postmenopausal women.